Analysis of PCB size reduction.
\r\n\tUnstoppable progress in the technologies of synthesis of diamond, graphene, and its compounds with stable parameters will provide materials for the industry of devices for integrated, radio, Opto- and quantum electronics and photonics.
\r\n\tIn most electronic and optical properties, diamond and graphene are superior to traditional and perspective semiconductors. It is safe to say that silicon and gallium arsenide are materials for electronics and optoelectronics of the past, gallium nitride and silicon carbide are high-tech today, and diamond and graphene are the future of electronics and photonics.
The electronics industry is the largest and fastest-growing manufacturing sector in the world. The PCBs are waste sources from electronic machines such as television boards, CD players, and cell phones. Researchers have reported that in recent years, the average rate of PCB development has risen by 8.7% due to technological progress. The studies observed that the continuous increase in e-waste generation rates is due to the nation’s population and technological growth. The studies predict that each individual would produce approximately 5173 kg of e-waste per year. The metallic composition consists primarily of 10–30% of copper (Cu) and other metals such as tin (Sn), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), silver (Ag), cadmium (Cd), gold (Au) and others, depending on the sources of printed circuit boards (PCB) [1, 2, 3]. A sample PCB is shown in Figure 1. Informal processing of e-waste in developing countries can lead to adverse effects on human health and environmental pollution. In 2016, 44.7 million metric tons of e-waste were generated globally [4, 5]. Health symptoms like headaches, dizziness, irritation in the eyes, nose, mouth, etc. are caused by exposure to Cu, which is present in landfills [6, 7, 8]. The methods that can be used to recover metals from PCBs are essentially physical, mechanical and chemical separations. Several studies on the feasibility of metal recovery from PCBs have been investigated in the last decade. Hydrometallurgical procedures, such as leaching, are very intentional in these studies.
Diagram of e-waste sources in various aspects and health effects.
E-waste not only includes household and industrial electrical appliances but also includes their components such as batteries, capacitors, castings, etc. Recycling of such waste has been carried out both formally and informally in several countries like China, India, Ghana, Thailand, Vietnam, etc. [9]. Traditional recycling techniques are well developed techniques to ensure safe and efficient separation, but are highly expensive to install and run. So such techniques are not taken into consideration and cheap informal techniques are to be implemented. This may cause the release of several pollutants into the environment, which can lead to a variety of health problems [8, 9, 10]. The metals present in the PCBs are highly toxic and hazardous to living bodies. These metals follow media such as dust, air, water, and soil to reach the human frame. Exposure to metals such as lead (Pb) and cadmium (Cd) affects reproductive health, growth, and mental instability and damages human DNA [11, 12, 13]. Health symptoms like headaches, dizziness, irritation in the eyes, nose, mouth, etc. are caused by the exposure to copper (Cu) which is present in landfills [14, 15, 16]. The different e-waste sources, heavy metals, and effects are explained in Figure 1.
Informal treatment strategies as well as innovative metal recovery approaches based on the material composition present in PCBs are accompanied by management and sustainable treatment techniques involving the reduction of waste circuit boards in developing countries. There are two techniques used to dispose of and extract heavy metals from PCBs. Incineration was used as a primary method through high-temperature PCB melting and is very hazardous as it releases strong toxic metal vapors such as polycyclic aromatic hydrocarbons and dioxins due to the emission of possible contaminants during incineration [17, 18], and the secondary method was followed at low temperature by hydrometallurgical techniques with the help of chemical reagents [19, 20, 21].
Pyrometallurgical processing is the most common method used for the separation of heavy metals from PCBs. The smelting process consists of the melting of waste PCBs in a high-temperature furnace (up to 1500°C) and is primarily used for the recovery of copper from used waste circuit boards. The limitations of this process are relatively low performance, high energy consumption, and difficulty in distinguishing metallic and non-metallic components [19, 22]. The pyrometallurgy process involves the heating of e-waste at a high temperature to recover precious metals. This treatment leads to the release of dangerous gases into the air, which must be extracted from the air by the flue gas cleaning system [23]. The limitations of this process are:
Pyrometallurgical techniques have a greater environmental impact due to the gaseous emissions from incineration.
Plastic recovery is not possible due to the replacement of plastics by coke as a source of energy.
Hazardous emissions such as dioxins are generated during the smelting of feed materials which have halogenated flame retardants and polyvinyl chloride (PVC), which lead to dioxins in the form of dioxins. Therefore, special installations (emission controls) are required to minimize environmental pollution.
It is very difficult to separate all the metals.
Low metals are recovered only by a fraction of metals.
The process has high energy consumption.
The hydrometallurgical method includes the application of aqueous solution leaching media, such as strong acid or base, oxidizing agents, and complexion agents, for the recovery of heavy metal separations. Previous studies have employed various leaching media such as strong acids (sulfuric acid, nitric acid), bases (sodium hydroxide, sodium hypochlorite), and complexing agents (cyanide, thiosulphate). This treatment approach has advantages over pyrometallurgical processes such as reduced pollution, radioactive contaminants, and moderately toxic chemicals for environmental effects. Therefore, these various recovery methods used for the treatment of used PCBs need to be reconsidered due to the enormous amount of flammable, toxic, and corrosive reagents used and the large volume of effluents and other solid waste produced [24]. In hydrometallurgical procedures, the following steps are widely used: leaching and extraction, purification, and concentration of liquefied solutions, as well as the recovery of heavy metals. Four operations are typically implemented in these recovery operations, as shown in previous studies. The hydrometallurgical procedure, such as leaching, has shown a great deal of strength in several studies. Several leaching reagents demonstrate major improvements in metal recovery. When treated with different acidic media, aq.HNO3, aq.HCI, and aq.H2SO4, PCBs were cut to remove Cu
The amount of Zn and Pb leached was very small when compared to the typical PCB metal content. The recoveries for Cu, Pb, Zn, and Sn were 16, 2.0, 1, and 1%, respectively, when leaching was done in crushed PCBs (size between 0.43 and 3.33 mm) using sodium cyanide solution [25]. It has the least compositional value compared to the average weight of the total metals found in it. After 480 min, various metals leached from PCB waste, such as H2SO4 and H2O2, provide 76% Zn, 85% Cu, 82% Fe, 77% Al, and 70% Ni recovery [26]. Other valuable metals are retained in the leaching solution as residue. The effective treatment of PCBs will depend on choosing the suitable recovery method. The development of new technology for the recovery of toxic heavy metal ions from waste PCBs remains an important scientific endeavor. The literature study shows the more stable and effective metal ion recovery will be achieved by two-stage chemical leaching with adsorption from waste PCBs. However, a suitable carrier has to be selected for the selective recovery of heavy metals in an effective manner.
This chapter presents an overview of current e-waste scenario, its impacts and treatment methods. The experimental studies are carried out for the the extraction of copper (Cu), tin (Sn), zinc (Zn) and lead (Pb) from PCBs by leaching using aqua regia (a mixture of HCI and HNO3 and HCI and H2SO4) for varying conditions of temperature, size of sample, contact time and shaking speed.
The main objectives of the present study are:
To prepare the suitable leaching agents in chemicals and optimize the operational parameters like concentration, temperature, shaking speed, time of leaching, and bulk density for the recovery of metal ions such as copper, zinc, tin, and lead separate from PCBs.
To determine the stability of the prepared leaching media by the recovery rate with the help of EDXs.
The waste PCBs are obtained from the e-waste disposal unit in India. The sample was initially cleaned manually to remove dust particles by the air blower. Later, other elements such as capacitors, resisters, integrated circuits, diodes, transistors, etc., were detached with the help of mechanical tools (saw metal cutter, sheet metal cutter, metal lathe cutting tool, cutting pliers, and materials separation toolkit). This separation is not as simple due to the difference in the physical characteristics of metals and non-metals. Hence, different separation methods, such as pneumatic separation, magnetic separation, filtering, eddy current separation, electrostatic separation, etc., are used to enrich metals and non-metals [10, 14, 23, 27].
The crushed PCBs obtained from the crusher are then pulverized and further exposed to milling operations for better size reduction using a ball mill, and particles of different mesh sizes are analyzed. The weight fraction of crushed PCBs obtained from the lower screens of jaw crushers with a capacity of 80 kg hr.−1 and a clearance of 10 mm is much lower, making better ion recovery impossible. Thus, it is subjected to 5 mm of clearance in the same jaw crusher, yielding samples weighing 65, 53, 48, and 36 grams for sieves with mesh sizes of 0.3, 0.18, 0.05 mm, and pan, respectively, when screened using a rotary sieve shaker at a speed of 60 rpm with a power of 0.25 HP and a single-phase 80 volt supply. As the reduction in size increases the rate of recovery of metal ions [16], the resulting crushed samples are processed into powder form using a pulverizer with a disk diameter of 175 mm operated by a 3-phase motor at 1400 rpm in a 225–445 V supply (Figure 2 and Table 1).
Stepwise size reduction of PCBs under the various mechanical operations (jaw crusher, roll crusher, furnace and pulverized mills produced small sizes between 4 and 0.05 mm) and heavy metals presents before leaching by SEM with EDx analysis.
Mesh size | Weight fraction (grams) | ||||
---|---|---|---|---|---|
Jaw crusher | Pulveriser | Ball mill | |||
B.S.S | (mm) | Clearance 10 mm | Clearance 5 mm | Feed size 6 mm | Ball weight 500 g |
4 | 4 | 155 | 118 | 45 | 27 |
7 | 2.3 | 125 | 92 | 57 | 35 |
25 | 0.6 | 95 | 76 | 69 | 58 |
52 | 0.3 | 52 | 65 | 87 | 64 |
85 | 0.18 | 30 | 53 | 60 | 78 |
300 | 0.05 | 22 | 48 | 85 | 82 |
pan | _ | 15 | 36 | 79 | 120 |
Analysis of PCB size reduction.
The leaching media is an important factor that should be considered while extracting heavy metals from PCBs. Various sorts of leaching agents show different leaching rates with respect to the type of metals present in PCBs. H2SO4, HCI, NaCl, HNO3, Na2S2O3,etc. are commonly used leaching media for the extraction of heavy metals from PCBs. Aqua regia, which is a mixture of hydrochloric acid and nitric acid, is used as a leaching agent in this study. It is prepared by mixing HCI and HNO3 in a 3:1 ratio under specified conditions of temperature, time, and surrounding conditions. Different leaching agents show different rates of recovery and metal extracted with respect to the nature of the leaching media, rate of ion exchange, degree of dissociation of ions and various parameters such as time, temperature, concentration etc. When remaining constraints are held constant, metal ions such as Cu+, Zn+, Pb+, and Sn+, among others, exhibit different ionic properties with acid medium. Even though the above studies result in significant metal recovery, they also possess demerits, such as the targeted extraction of a specific metal leads to the loss of several other valuable metals. By using aqua regia as a leaching reagent, heavy metals such as Cu, Sn, Pb, and Zn can be extracted from PCBs with a high recovery rate. Aqua regia preparation involves the mixing of strong acids. It produces heat and toxic gases, so it is necessary to follow safety protocols while preparing and handling this solution. In this experiment, HNO3 is added to HCI contained in a beaker, which is placed in a water bath in order to reduce the fume generation. The two concentrated acids are mixed in the ratio of 3:1 (HCI:HNO3); concentrated HCI is about 35% and concentrated HNO3 is about 65%. So that volume ratio will be 4 parts concentrated HCI and 1 part concentrated HNO3. The solution is kept away from organic contaminants because it leads to vigorous or violent reactions and a low temperature should be maintained.
All the experiments are carried out in a conical flask incorporated with a temperature-controlled shaker. Primary analysis was conducted by applying specific conditions to obtain a standard recovery rate. 5gm of PCB samples are allowed to react with 20 ml of leaching media inside the conical flask at 60°C and shaken in a mechanical shaker at a shaking speed of 120 rpm for 2 hrs. At the end of this effective contact time, the shaker is stopped and the solution in the conical flask is filtered using filter paper. After complete filtration, the filtrate is sent for SEM with EDX analysis to determine the composition of metals retained. The rate of leaching is affected by a number of factors, including sample size, concentration, temperature, shaking speed, and contact time. By varying these parameters, different values for the recovery rate and composition of heavy metals are obtained.
It is important to conduct sample analysis before subjecting the crushed samples to the leaching process. The primary sample had followed three size reduction operations, namely crushing, pulverizing, and milling, and the weight fractions obtained at each operation are explained with their corresponding mesh size shown in Figure 3. The ultimate purpose of size reduction has been studied previously and data analyzed.
Graphical representation of size reduction in different operation.
The graphical representation of size analysis shows that the fraction of sample obtained in the sieves with larger mesh sizes has been decreasing when subjected to a sequence of size reduction operations. However, the total weight obtained in the sieves is approximately conserved with a trace of negligible loss. From the sieve analysis data of each operation, the sample obtained from the ball mill has a fraction of weight in the pan that is less than 0.05 mm. Various studies used shredded samples with a size of less than 0.5 mm, which resulted in a high recovery rate of heavy metals [4, 5]. Present research comprises leaching particle sizes of 0.05 mm and 0.1 mm, which is the sample retained just above the pan (Figures 4 and 5).
Presents of metal components from PCBs by the EDXs.
Graphical representation of % recovery of metals with concentration.
By varying the concentration, the leaching process shows a significant change in the recovery rate. The recovery rate increases with an increase in the concentration of the sample with respect to time. After attaining an equilibrium state, the rate of leaching becomes constant. 20 ml of aqua regia is used to leach heavy metals from 2, 4, 6, 8, and 10 g of 0.3 mm sized PCB samples at standard conditions of 80°C of temperature and 200 rpm of speed for 2 hrs. The graph shows an increase in the recovery rate of metals with an increase in the concentration of PCB. The metals recovered in the decreasing order of Cu, Pb, Sn, and Zn were recovered. Copper is the most recovered metal, whereas zinc is the least recovered. When the concentrations were increased by 0.1 g ml˗1, all metals showed a slight increase in recovery rate.
As there is no decrease in the percentage of metals recovered, it is confirmed that the metallic distribution of powdered PCBs is uniform. When the concentration is 0.5 g/ml, the graph shows the maximum recovery with metallic composition as 92.06% of Cu, 55.42% of Sn, 48.27% of Zn, and 78.42% of Pb. Based on the previous studies of metal recoveries [28, 29].
The different sieve size particles are leached using aqua regia and the weight fraction of metallic components is analyzed. 5 gm of particles with sizes of 4, 2.3, 0.6, 0.3, and 0.05 mm are leached for hours at 80°C with a shaking speed of 200 rpm. Figure 6 explains the relationship between size and recovery. It shows recovery increases with an increase in contacting surface.
Graphical representation of % recovery of metals with size.
The graph shows an appreciable increase in the percentage of metals recovered with a decrease in the size of the sample. The higher recovery rate is shown for the PCB sample at the lowest size, which is 0.05 mm. The uniformity of metallic distribution is also conserved here. Copper is the major component present in the leached sample and zinc is the minimum. It results in a percentage recovery of copper, tin, zinc, and lead of 83.49, 58.72, 57.75, and 78.42%, respectively.
5 gm of PCB samples of size 0.3 mm are treated with aqua regia in a conical flask and shaken at a speed of 200 rpm for 2 hrs. Five samples of the same condition are maintained at varying temperatures of 40, 60, 80, 100, and 120°C. After completion of effective time, the leached PCB sample is analyzed. The data obtained is represented graphically and the relations between recovery and temperature are studied. The graph shows an appreciable increase in recovery rate with an increase in temperature for a particular point of temperature [30, 31]. When the sample is leached at a temperature above 80°C, there is no appreciable change in recovery, which is negligible. It indicates that the leaching depends on temperature only for a particular limit, and that after a certain point of temperature, leaching is independent of temperature. At 80°C, the result shows a metallic composition of 89.84% of Cu, 69.05% of Sn, 65.51% of Zn, and 82.45% of Pb (Figure 7).
Graphical representation of % recovery of metals with temperature.
To determine the effective leaching time, the sample is allowed to be leached for different intervals of time. The persistent condition is maintained as a 5gm sample of size 0.3 mm shaken with 20 ml of aqua regia in a conical flask and shaken at a speed of 200 rpm while the temperature is maintained at 80°C. Then it is allowed to be leached for 1, 2, 3, 4 and 5 hrs, respectively. The data collected is graphically represented in Figure 8 below. It shows that the recovery percentage is almost constant when a sample is leached for more time after a certain period of time. The graph shows that the recovery of metals increases with an increase in time for a certain period, and after a particular point of time, the recovery becomes almost constant. That means all the metals in contact are leached from the sample within a particular time period, and there is no use in leaving the system under leaching condition after a certain period of time. The results show the maximum recovery when the sample is leached for 3 hrs. When the sample is leached for 3 hrs, the result shows the recovery of metals as 91.36, 69.43, 72.41, and 83.22% of Cu, Sn, Zn, and Pb, respectively.
Graphical representation of % recovery of metals with time.
Once all the results for recovery with respect to various parameters are evaluated and studied as explained above, we get the optimum condition to obtain maximum recovery of metals. The optimum condition is the value of concentration, size, temperature, shaking speed, and time at which the maximum recovery is obtained. The results obtained at optimum conditions show that the recovery of heavy metals is as high as 99.9% of copper, 98.3% of lead, 96.8% of tin and 93.1% of zinc, respectively. In this study, specific conditions of 800°C, 0.05 mm of thickness, 3 hours of contacting time, 80 rpm shaking speed, and pulp density of PCB sample of 20gm L−1 were met in both stages, with a 3:1 ratio of first stage HCI and HNO3 and second stage HCI and H2SO4) prepared as a leaching agent. The experimental results were obtained under the above mentioned conditions and have been shown in (Figure 9) and (Table 2). Results found that the optimum recovery rate for stage I Cu was 89.5%, Sn 64.4%, Zn 63.4%, Pb 80.9%, and stage II Cu was 99.0%, Sn 96.8%, Zn 93.1%, and Pb 98.3%, respectively.
EDXs spectrum analysis for metal ions obtained after leaching.
Metals | Initial CO | Stage-I & II weight fraction | % Recovery | ||||
---|---|---|---|---|---|---|---|
Ce-I (PCBs sample) | Ce-I Leached solution | Ce-II (PCBs sample) | Ce-II Leached solution | Stage-I | Stage-II | ||
Cu | 3.15 | 0.325 | 2.825 | 0.031 | 3.119 | 89.5% | 99.0% |
Sn | 42.40 | 15.09 | 27.31 | 1.36 | 41.04 | 64.4% | 96.8% |
Pb | 27.81 | 5.31 | 22.5 | 0.47 | 27.34 | 80.9% | 98.3% |
Zn | 1.16 | 0.403 | 0.757 | 0.076 | 1.084 | 63.4% | 93.1% |
Others | 27.81 | 12.4 | 15.41 | 1.168 | 26.642 | 52.6% | 95.4% |
Metallic composition of leached PCBs at optimum conditions by stage-I & II.
The study shows the dependency of the rate of recovery on the condition in an arbitrary manner. The recovery rate has a different approach with each parameter. The results show that the maximum percentage of metals recovered at 80°C, 0.05 mm thickness, 3 hours of contacting time, 80 rpm shaking speed, and PCB sample concentration of 0.5 g/ml−1.Under this condition, the resultwas obtained with 97.59% of copper, 96.29% of lead, 94.66% of tin, and 96.64% of zinc, respectively. It is the most effective recovery condition for this experiment. However, targeted extraction of a particular metal can be made possible by varying a particular parameter only. In such a way, the percentage recovery of that particular metal can be increased with negligible loss. In such extractions, the other heavy metals are retained in the sample or less amounts of other metals are separated. Disposal of such residuals also causes environmental issues. Since this type of extraction is promoted in order to reduce the environmental problems caused by these kinds of heavy metals, the targeted extraction of a particular metal is not advisable, even if it is economically profitable. It was concluded that the combination of aqua regia (HCI and HNO3 and HCI and H2SO4) leaching is an effective and economic way for the recovery of copper from leached solution. According to studies, modifying the dissolving of metal ions in the reagents increases the rate of leaching, but this raises the total cost and results in the introduction of additional chemicals into the atmosphere. As a result, attempts will be made in the future to resolve these issues. Only a few field trials have been performed, and more systematic studies are needed to decide the best conditions for using aqueregia as a leaching medium.
This study was carried out with utilization of the laboratory facilities in Excel Engineeeringcollege, Tamilnadu, India. The corresponding author would like acknowledge and thank to his parents and brother P. Selvarasu, PG Assist Zoology, Govt Higher Secondary school, Vellore for their kind support.
The heavy metals in PCBs were leached with two-step aqua regia (HCI and HNO3 and HCI and H2SO4).
Optimization of various parameters has been tested to enhance the recovery of heavy metals.
The maximum recovery rates obtained were Cu 97.59%, Pb 96.89%, Sn 94.66%, and Zn 96.64%.
The combination of aqua regia leaching and PCBs is an efficient and cost-effective method for recovering heavy metals from PCBs.
Copper (–)
Electrical and electronic equipment (–)
Electronic waste (–)
Energy-dispersive X-ray spectroscopy (–)
Hydrochloric acid (–)
Polyvinyil chloride (–)
Lead (–)
Nitric acid (–)
Printed circuit boards (–)
Scanning electron microscopy (–)
Sulfuric acid (–)
Tin (–)
Waste of electrical and electronic equipment (–)
Zinc (–)
The concept of vascular dementia (VaD) is a diagnostic category that emerged in the late 1980s to characterize dementia secondary to cerebrovascular disease [1]. The construct was later expanded into the Vascular Cognitive Involvement complex (VCI), a continuum ranging from Vascular Mild Cognitive Impairment (VMCI) to dementia [2]. This chapter will comprehensively address the main clinical, diagnostic, and therapeutic aspects of VCI.
Recent studies estimated that between 5 and 7% of the world’s elderly population suffers from dementia, with a higher frequency in Latin America (8.5%) and a slightly lower prevalence in sub-Saharan Africa (2–4%) [3]. Considering the high social and economic impact of the condition, especially in these regions with fast population aging, knowledge of the epidemiology of dementia has become fundamental for planning health policies [4, 5].
From an etiological point of view, cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia, occurring both as a single mechanism of brain damage and contributing to cognitive decline in neurodegenerative dementias [6]. Cerebral arteriosclerosis was considered the leading cause of “senile dementia” until the 1960s when Alzheimer’s Disease (AD) became recognized as the most prevalent brain pathology affecting those individuals [7, 8]. Recently, cognitive impairment of vascular origin has once again attracted the interest of researchers, driven mainly by the growing concern with metabolic conditions (systemic arterial hypertension, diabetes mellitus, dyslipidemia and obesity) and their effects on target organs [9, 10]. The incidence rate of dementia appears to be declining in western developed countries, which has been hypothesized to result from continued improvements in older adult education and advances in health care, including efficiently controlling metabolic diseases [11, 12].
Challenges for understanding and interpreting the epidemiological aspects of VCI to include the lack of harmonization of the nomenclature and diagnostic criteria used in the studies. Table 1 lists some of the primary population studies produced between 2000 and 2012, which have estimated the prevalence of VaD in different countries. A meta-analysis reported that VaD occurs in 1.6% of individuals over 65 years of age and constitutes 26% of the total number of people with dementia in western countries [13]. Conflicting results across studies could be identified, mostly derived from different sources of diagnostic criteria employed: when the National Institute of Neurological Disorders and Stroke and
Country | Author, year | Sample (n) | Diagnostic criteria | Age (years) | Prevalence |
---|---|---|---|---|---|
China | Wang W et al., 2000 | 3728 | DSM-III-R, ICD-10 | ≥65 | 1.37% |
Zhang ZX et al., 2005 | 34807 | MINDS-AIREN | ≥65 | 1.1% | |
Zhao Q et al., 2010 | 17018 | DSM-IV, NINDS-AIREN | ≥55 | 0.79% | |
Jia J et al., 2014 | 10276 | DSM-IV, NINDS-AIREN | ≥65 | 0.79% | |
South Korea | Lee DY et al., 2002 | 643 | DSM-IV | ≥65 | 2% |
Jhoo JH et al., 2008 | 1118 | DSM-IV, NINDS-AIREN | ≥65 | 1% | |
Kim KW et al., 2011 | 8199 | DSM-IV, NINDS-AIREN | ≥65 | 2% | |
Japan | Yamada T et al., 2001. | 3715 | DSM-III-R, NINDS-AIREN | ≥65 | 1% |
Ikeda M et al., 2001 | 1162 | DSM-IV | ≥65 | 2.4% | |
Meguro K et al., 2002 | 1654 | DSM-IV, ADDTC, NINDS-AIREN | ≥65 | 1.6% (NINDS-AIREN) and 2.6% (ADDTC) | |
Wada-Isoe K et al., 2009 | 120 | DSM-IV, NINDS-AIREN | ≥65 | 1.7% | |
Thailand | Wangtongkum S et al., 2008. | 1492 | DSM-IV, NINDS-AIREN | ≥45 | 0.29% |
Sri Lanka | de Silva HA et al., 2003 | 703 | DSM-IV | ≥65 | 0.57% |
Turkey | Arslantaş D, Ozbabalik D, 2009 | 3100 | CID-10 | ≥55 | 4.29% |
Spain | Vilalta-Franch J et al., 2000 | 1460 | CAMDEN | ≥70 | 6.23% |
García García et al., 2001 | 3214 | DSM-III-R, NINDS-AIREN | ≥65 | 1.8% | |
Bofill E et al., 2009 | 877 | DSM-IV, NINDS-AIREN | ≥80 | 6% | |
Denmark | Andersen K et al., 2000 | 3346 | DSM-III-R | 65–84 | 1.3% |
Sweden | Börjesson-Hanson A et al., 2004 | 338 | DSM-III-R | 95 | 15.7% |
USA | Plassman BL et al., 2007 | 856 | DSM-III-R, DSM-IV | ≥71 | 2.43% |
Brazil | Herrera Jr. et al., 2002 | 1656 | NINDS-AIREN. | ≥65 | 0.66% |
Bottino CM et al., 2008 | 1563 | DSM-IV | ≥60 | 2% | |
Egypt | The Callaway HN et al., 2012 | 8173 | DSM-IV-TR | ≥50 | 0.64% |
Population studies of VAD prevalence.
One study demonstrated that 83.3% of individuals with dementia due to subcortical vascular disease initially presented focal or mild changes in cognition, with low impact on functionality, which would be analogous to the concept of Mild Cognitive Impairment due to AD [14]. Vascular Cognitive Impairment non Dementia, another construct of prodromal VaD, presented a prevalence of 2.6–8.5% in samples older than 65, configuring the most common clinical form among VCI cases [15].
In addition to etiological characteristics, other aspects may impact the prevalence of VaD in studies, such as age and geographic aspects, i.e., the inclusion of populations from long-term care facilities and the presence of comorbid brain conditions with neurodegenerative processes. Some studies demonstrated an increase in VaD prevalence with aging, although lesser than that observed in AD. It was suggested that the prevalence of VaD would double every 5.3 years, while AD would present a prevalence twice as high every 4.3 years [6]. Consistently, prevalence rates below 1% were identified in some studies that included samples younger than 65 years of age, whereas in a study evaluating a 95-year-old group, the prevalence was 15.7% (Table 1). However, conflicting results could be found in the literature on the relationship between aging and VaD. A European study, for example, showed that the prevalence of VaD reduced when populations aged 60 and 90 were compared—15 and 8.7%, respectively [16]. In addition, the variation in the prevalence of VaD between the eighth and tenth decades of life was not significant in one study (from 10.2 to 9.9%) [16, 17]. Mixed dementia, on the other hand, showed that prevalence between these age groups increased, advancing from 4.7 to 7.1% of subjects [16, 17]. Another study conducted in the USA showed that VaD was responsible for 21% of dementia cases among those 80 years of age, but this rate corresponded to only 16% of cases older than 80. Studies evaluating the prevalence of early-onset dementia (starting before 65 years old) have also documented controversial results. VaD was shown to be the leading cause of early-onset dementia in a Japanese retrospective study, affecting 42.5% of the cases [18], while a Spanish study, which evaluated the incidence of dementia in individuals aged 30–64 years, reported that VaD was responsible for only 13.8% of cases; therefore, occurring less frequently than AD (42.4%) and dementia secondary to general medical conditions (18.1%) [19].
Geographic issues may affect the prevalence of VaD across studies. Classical studies have recorded the high prevalence of VaD in Japan and China, which would account for 50% of dementia cases, overcoming the frequency of AD [13]. Recent studies, however, have not confirmed such findings. It is currently accepted that, as observed in other countries, AD is the most common etiology of dementia in these regions. Meguro et al. [20] have argued that epidemiological studies previously conducted in Japan had overestimated the occurrence of VaD, probably due to categorizing mixed dementia within the group with cerebrovascular-related cognitive impairments [4]. Consequently, VaD/AD prevalence ratios significantly decreased in individuals 75 years old or more in studies conducted in Japan from 1985 to 2005 (2.1 in 1985; 1.2 in 1992; 0.7 in 1998 and 0.7 in 2005) [21]. In Brazil, the prevalence of VaD ranged from 9.3 to 15.9% of dementia cases in population studies conducted in São Paulo state [22, 23, 24]. Studies evaluating differences between regions with different degrees of urbanization reported controversial results. The overall prevalence of dementia in rural areas of China was significantly higher than in urban areas (6.05% vs. 4.40%, P < 0.001), but this difference was not observed for VaD (1.28% vs. 1.61%, P = 0.166) [25]. Other authors, however, suggested that living in rural areas would double the odds of developing VAD (odds-ratio = 2.03) [26].
Comorbidity between AD and vascular brain lesions seems frequent.
Studies measuring the influence of gender on the prevalence of VaD also produced conflicting results. Moreover, systemic arterial hypertension may double the risk for VaD in females, but not in males, while physical exercises appear to protect women more efficiently than men from VaD [26].
Studies on the incidence of VaD are rare and conflicting in the literature. According to North American data, VaD, with or without associated AD component, has an annual incidence of 14.6 per 1000 people for Caucasians and 27.2 per 1000 people for African Americans [30]. According to studies, the incidence rates of VaD did not differ between men and women [27].
Cognitive alterations due to cerebrovascular disease (CVD) have been classified within a continuum named Vascular Cognitive Impairment (VCI), and the term VaD is currently reserved for the stages in which such deficits reach dementia severity [2, 31]. The concept of VCI involves presymptomatic presentations with high risk for cerebrovascular disease (“brain-at-risk”), as well as cases of cognitive impairment of vascular etiology that do not meet criteria for VaD, referred to as Vascular Cognitive Impairment No-Dementia (V-CIND) or Vascular Mild Cognitive Impairment (VaMCI) [6, 32].
VCI encompasses a combination of various types of cerebral vascular lesions, i.e., multiple cortical or subcortical infarctions, strategic infarctions, microangiopathic lesions of white matter, base nuclei hypoperfusion lesions, and hemorrhagic lesions [31]. As a result of the array of pathological processes leading to parenchymal damage, heterogeneous clinical presentations, including motor, cognitive and neuropsychiatric manifestations, could be identified. Hence, to enable a didactic approach to these conditions, some authors have sought to define VCI subsyndromes based on the mechanism of vascular brain injury, which generated the concepts of “dementia by multiple infarctions,” “dementia by strategic infarction,” and “vascular dementia by subcortical ischemia.”
Dementia due to multiple infarctions results from disease of the large cerebral vessels, resulting mainly from vascular thromboembolism. Cortico-subcortical infarctions of variable extension are observed [33]. Symptoms typically start abruptly and evolve in a stepwise pattern, succeeding ischemic brain events. With the accumulation of brain lesions, the patient begins to develop focal neurological signs, such as asymmetric reflexes, pseudobulbar syndrome (i.e., difficulties swallowing and speaking, in addition to effective lability), the release of primitive reflexes (such as Babinski reflex), and sensory abnormalities [33].
Dementia by strategic infarction is understood as a single lesion (or few lesions), which occurs in a functionally important location. It may result from cortical or subcortical infarction, whether unilateral or bilateral. Examples are dementias resulting from thalamic or hippocampal infarction [33].
Dementia due to subcortical ischemic vascular disease (SIVD) is the most frequent subtype of VaD, and it is associated with changes in small cerebral vessels (perforating arteries) disease, secondary mainly to hypertensive arteriopathy. It covers two clinical subsyndromes: Binswanger disease and lacunar state. Binswanger disease consists of dementia due to large subcortical infarctions, while in lacunar infarcts, multiple punctiform or rounded lesions are observed in the cerebral parenchyma. The clinical picture is usually insidious in most cases.
VaD due to subcortical ischemia may also be associated with the presence of a mutation in the NOTCH3 gene, of autosomal dominant transmission, causing the disease known by the acronym CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). This disorder presents as VaD by multiple subcortical infarctions of presenile onset. Symptoms include, in addition to severe cognitive deficits, the presence of migraine with aura, mood swings, and apathy.
The most used diagnostic guidelines for the detection of VaD are summarized in Table 2. Except for Hachinski’s Ischemic Score (HIS), based solely on clinical criteria, the diagnosis of VAD depends on the demonstration of cognitive deficits through neuropsychological testing and the relationship between cognitive impairment and the vascular brain alterations identified to neuroimaging. The definition of dementia varies according to the criteria employed, leading to difficulties interpreting the results of studies that use different diagnostic systems.
Diagnostic criteria | EIH (1975) | ADDTC (1992) | CID-10 (1992) | NINDS-AIREN (1993) | ASA/AHA (2011) | DSM-5 (2013) |
---|---|---|---|---|---|---|
Clinical criteria | Abrupt onset, “stepwise” evolution, fluctuation, nocturnal confusion, personality preservation, depression, somatic complaints, emotional lability, arterial hypertension, history of stroke, focal symptoms, focal signs, other signs of arteriosclerosis | Cognitive decline in more than one domain, CVD (demonstrated by a history of two or more vascular events, focal neurological signs, or one stroke with a clear temporal relationship with cognitive alterations), functional impairment, high HIS, history of TIAs, history of risk factors for CVD (hypertension, diabetes, heart disease) | Impairment of memory and intellectual activities (thinking, reasoning, and flow of ideas), with consequent functional impairment, absence of disturbance of consciousness, deterioration of emotional control, social behavior and motivation, focal neurological signs, deficits present for at least six months. | Memory impairment +1 other cognitive domain, functional impairment, focal signs, the onset of dementia up to 3 months after stroke, abrupt onset, fluctuating course or “stepwise progression,” other signs suggestive of CVD (gait disorders, falls, change in urinary frequency or urgency, pseudobulbar paralysis, abulia, depression, emotional incontinence, psychomotor retardation, executive dysfunction) | Impairment in two or more cognitive domains demonstrated by tests, functional impairment; a clear temporal relationship between deficits and vascular event or a clear relationship between severity and pattern of cognitive impairment; the presence of subcortical and diffuse CVD, absence of progressive evolution of deficits suggestive of neurodegenerative disorder | The onset of symptoms related to one or more vascular brain events, evidence of a more prominent decline in attention (including processing speed) and executive function, CVD by history, physical examination, and neuroimaging |
Laboratory criteria/neuroimaging | — | Evidence of 2 or more areas of vascular lesions at neuroimaging, evidence of at least one vascular lesion (in non-cerebellar location), presence of multiple infarctions | Presence of cortical, subcortical, or mixed infarctions | Evidence of CVD to neuroimaging, two or more ischemic events, severe territorial, strategic, or subcortical infarction | Evidence of CVD to neuroimaging | Evidence of CVD to a degree sufficient to cause cognitive symptoms, significant brain parenchyma injury, genetic evidence of CVD |
Diagnostic criteria for vascular dementia.
Although the evolution of knowledge about the clinical and neuroimaging characteristics of VCI has led to the improvement of diagnostic guidelines, some questions remain. The HIS, elaborated in 1975, was one of the first instruments to suggest a differentiation between “dementia by multiple vascular infarctions” and “primary degenerative dementia” through clinical criteria. Among them, the items “abrupt onset” and “stepwise evolution” refer to the pattern of cognitive deficits that follow episodes of vascular ischemia (e.g., vascular brain ictus). Following this principle, more recent diagnostic guidelines require a temporal relationship between vascular events and cognitive impairment. However, recognizing subcortical ischemic disease as a cause of dementia of insidious evolution makes it necessary to adapt the criteria for the best detection of this type of condition. In addition, the memory impairment requirement, present in ICD-10 and NINDS-AIREN, derives from an approximation between VaD and more specific cognitive attributes of AD. The DSM-5, published in 2013, has brought advances in this aspect, highlighting the presence of compromises in attention, processing speed, and executive function. Another data that deserves attention is the inaccuracy of neuroimaging criteria since the extent of white matter lesions necessary to generate cognitive alterations with dementia severity is not defined by the classification systems. Finally, the requirement of deficits in at least two domains is consensual among the most recent diagnostic guidelines. However, the cut-off point for cognitive impairment is not established. The National Institutes of Health (NIH) defined the cognitive impairment due to dementia as a cognitive performance of two standard deviations below normative data in at least two cognitive domains, albeit further studies are needed to evaluate the validity of these criteria.
Predementia cognitive alterations of vascular etiology began to draw the attention of researchers in the late 1990s when Bowler’s studies warned of the importance of an early diagnosis for VCI [31]. Although the authors already pointed to the need for new diagnostic criteria that included the initial stages of the condition, early studies with Mild Cognitive Impairment (MCI) sought their similarities with AD [34]. In 2003, a study group meeting in Stockholm expanded the concept of MCI to include the “non-amnesic” form of the disorder in the diagnostic criteria [34]. Petersen’s diagnostic guidelines published in 2004 placed the MCI as a risk factor for dementia of different etiologies. In vascular conditions, amnestic or non-amnestic MCI with multi-domain involvement would tend to progress to VaD [34]. However, this initial model only included cognitive and functional aspects, not defining neuroimaging criteria for the condition. In 2011, the diagnostic criteria for VMCI were published, developed by the American Heart Association and the American Stroke Association, inspired by the algorithm for detecting VaD proposed by these same entities [6]. The Vascular Cognitive Impairment No-Dementia (VCIND) construct is a more comprehensive concept than the VMCI, since it encompasses a wide range of conditions affecting cognition in the late life, including focal cognitive deficits, genetic disorders, and cognitive alterations secondary to psychiatric disorders. However, a review of the concept of VCIND, proposed by Zhao et al. restricted this construct to bring it closer to the concept of VMCI [35]. The DSM-5 established the diagnostic guidelines for the Mild Neurocognitive Disorder of vascular etiology, defining it as the presence of subtle cognitive impairments due to cerebrovascular disease [36].
Dementia associated with multiple mechanisms of brain damage, such as vascular-related and neurodegenerative processes, has been classified as Mixed Dementia (MD). Despite its increasing prevalence, the concept of MD lacks a clear definition. The HIS conceptualizes MD as an intermediate clinical state with both VaD and AD characteristics [33]. The NINDS-AIREN (1993) did not establish diagnostic criteria for DM, recommending the term “AD + Cerebrovascular disease” [37]. ICD-10 proposed that the diagnosis of MD should be established if the subject fulfilled the criteria for both AD and VaD [38]. The DSM-5 does not present a diagnosis characterization of DM but indicates the possibility of a simultaneous diagnosis of VAD and AD [36].
In addition, diagnostic definitions of VCI generally require observing cognitive dysfunction, vascular risk factors, vascular brain lesions, and focal neurological findings [39]. A classic presentation with stepwise evolution can be found in large-vessel disease [33]. Table 3 summarizes these aspects.
Risk and etiological factors | Age of onset | Neuroimaging | Clinical features | |
---|---|---|---|---|
Multi-infarct | Hypertension, heart disease, diabetes, coronary disease | From the 4th decade | Cortical lesions and/or white matter and basal ganglia; commitment of the anterior, posterior and middle cerebral arteries | Executive dysfunction, apathy, impairment in attention depression, psychomotor slowing |
CADASIL | Mutation of the NOCHT 3 gene | 3–4th decades | Hyperintensities in the temporal subcortical region | Migraine, executive dysfunction, family history |
Binswanger | Age, hypertension, diabetes | Between 4 and 7th decades | Extensive and diffuse lesions in the subcortical region | Insidious progression, mood swings, psychomotor slowing apathy, motor changes |
Lacunar infarctions | Cardiac arrhythmias (atrial fibrillation), heart disease, hypertension | From the 4th decade. Present in up to 30% of individuals over 30 years of age | Lesions in areas adjacent to the lateral ventricles, basal ganglia, thalamus, inner capsule, bridge, and cerebellum | “Silent infarctions”; the presence of risk factors, varied clinical and related to the topography of lesions. |
Clinical and radiological features of VaD.
Hypoperfusion related to atherosclerosis and arterial sclerosis, hypotension associated with reduced cholinergic activity, altered autonomic regulation, cortical hypometabolism, disruption of the neurovascular unit, and cardiovascular events such as congestive heart failure, with consequent systolic dysfunction and embolism is among the main events related to cerebrovascular disease and cognitive decline [6, 40]. Vascular lesions may cause impairment in cholinergic function and disconnection of frontal limbic associative fibers. Cholinergic tracts integrate different brain areas, participating in vasomotor control and cognitive and behavioral modulation [33].
SIVD is commonly observed in MRI in the form of subcortical hyperintensities. It results from the interplay of multiple risk factors affecting cerebral small vessels, such as dyslipidemia, hypertension, heart disease, genetics, and diabetes mellitus. Microstructural abnormalities usually comprise gliosis, demyelination, and axonal damage of subcortical connections. White matter lesions, known as leukoaraiosis, may be related to apathy, executive dysfunction, depression, motor alterations, and urinary control and have been considered a reliable predictor for progression to dementia [41]. Studies have shown that extensive white matter lesions, characterized by a score equal to 3 on the Fazekas visual scale, may have a death or disability rate of 29.5%. On the other hand, the identification of leukoaraiosis at MRI may not be exclusively suggestive of SIVD. Additional pathological processes, including inflammation (e.g., multiple sclerosis and neurosarcoidosis), autoimmune diseases (celiac disease), and inherited metabolism errors (leukodystrophy), may appear hyperintense at neuroimaging.
Cognitive impairment resulting from SIVD may increase the risk for conversion into dementia and directly cause cognitive decline. Executive dysfunction, attention deficit, processing slowing, and visuospatial alterations are frequently observed [36]. Memory impairment tends to be less severe than AD, as it mainly affects free recall and usually spares recognition, and patients can benefit from clues. Apathy, depression, and anxiety are standard features of SIVD. Possibly, a relationship between the extent of the lesions and the location exists with the severity of dementia.
Binswanger disease is characterized as damage of 25% or more of the subcortical region [42]. It is characterized pathologically by thickening the walls of the small arteries with fibrinoid necrosis of large caliber brain vessels [43].
Vascular risk factors (VRF) encompass disorders with an increased chance of developing brain vessel pathology and circulatory disorders, with eventual nervous tissue damage (CVD), leading to CCV14 [44].
The VRF comprises various causes (genetic, metabolic, cardiovascular, lifestyle, others) underlying the vascular pathology and eventually the nervous tissue supplied by the vascular territory. They can be divided into non-modifiable, currently without adequate treatment or prevention (e.g., genetic [cerebral amyloid angiopathy, CADASIL, Fabry disease]) and modifiable, i.e., amenable to treatment and prevention (e.g., metabolic, cardiovascular) [45, 46, 47] (Table 4). The various VRF, including genetic diseases, and vascular pathologies, such as embolisms, cerebral blood flow, and perfusional changes, must be considered.
Metabolic | Cardiovascular | Lifestyle | Others |
---|---|---|---|
High cholesterol Diabetes mellitus Metabolic syndrome High homocysteine Obesity | Arterial hypertension Arteriosclerosis Atrial fibrillation Coronary disease Carotid stenosis Myocardial inflammation Valvulopathy Patent foramen ovale | Tobacco smoking Alcoholism Sedentarism Inadequate diet | Psychological stress Depression Sleep apnea Low education Heart surgery Vasculitis |
Modifiable vascular risk factors.
Anamnesis should investigate vascular risk factors, including arterial hypertension, dyslipidemia, diabetes mellitus, and sickle cell anemia [33]. Previous personal or familial history of vascular brain events should be characterized. Lifestyle habits, including alcohol and tobacco consumption and unhealthy diet, are strongly associated with VCI.
Clinical evaluation should also be directed to screening cognitive symptoms, especially to difficulties for goal-directed behaviors and sustained attention, as well as for deficits in cognitive speed [36]. Other abnormalities may include problems remembering recent events, difficulties organizing the personal agenda and planning tasks, reduced verbal fluency, and impaired spatial orientation. Behavioral changes, either sudden or insidious, such as irritability, reduced general interest, and social isolation, often indicate depressive symptoms. In addition, personality changes, visible in social situations where the behavioral pattern is beyond the usual, may denote changes in brain function. A third component aspect of anamnesis is functional assessment, which addresses the degree of autonomy for resolving indoor or outdoor tasks, such as making a meal, paying bills, or dealing with money. For greater diagnostic accuracy, it is always desirable to have a companion throughout the examination, preferably those with recurrent or continuous contact, considering the possibility of cognitive impairment in the patient.
The detailed neurological clinical examination should be guided by investigating comorbidities such as hypertension, atrial fibrillation, dehydration, infection, delirium, number of prescribed medications, alteration of sphincter control, motor difficulties or speech articulation, the occurrence of falls, as sudden changes in the level of consciousness.
The neuropsychological and clinical characteristics of VaD vary depending on the location and extent of the lesions. Neuropsychological evaluation analyzes the repercussions of brain lesions and dysfunctions on the cognition and behavior of the patient [48]. The differential diagnosis of AD and VaD, the most frequent types of dementia, can be challenging; as previously mentioned, those two pathological processes may share similar clinical characteristics, and they may co-occur [1]. In addition, neuropsychological evaluation may help assess clinical status, contributing to planning therapeutic strategies and family guidance [49]. Some of the main findings on neuropsychological differences in the most homogeneous group of SIVD and AD are summarized in Table 5.
Cognitive function | SIVD | AD |
---|---|---|
Memory |
|
|
Language |
|
|
Executive functions |
|
|
Differential diagnosis of VAD and AD according to cognition.
Different guidelines recommend the use of neuroimaging for the characterization of cerebrovascular disease [6, 39, 50, 51, 52, 53]. Initially, as proposed by the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network in 2006, these methods were recommended solely in research settings [50]. In 2011, with the American Heart Association/American Stroke Association recommendations, neuroimaging became a critical diagnostic tool in clinical practice [6].
Computed tomography (CT) is sufficient to rule out other causes of cognitive decline besides VCI, such as tumor processes, subdural hematoma, or hydrocephalus. Lacunar infarctions and, to a lesser extent, subcortical lesions can be seen on CT. The detection of vascular brain disease by magnetic resonance imaging (MRI) is made through T2 and Flair-weighted images (Figures 1 and 2), the latter being the preferred sequence for identifying subcortical hyperintensities. In the case of thalamic strategic infarctions, the T2 sequence can contribute to its more precise location. Micro bleeds and calcifications may be better detected with the use of T2-weighted images. The finding of watershed infarcts between the anterior and middle cerebral artery is usually seen in the dominant hemisphere, in the case of anterior cerebral artery flow territories, bilaterally, preferably by FLAIR sequences.
The proportion of white matter hyperintensities to magnetic resonance imaging with FLAIR sequence. The score on the Visual Scale of Fazekas for light (A), moderate (B), and advanced (C) levels were corresponding to the score of 1, 2, and 3, respectively.
Flair image (A) shows cortico-subcortical infarction on the right, corresponding to the anterior cerebral artery territory with caudate nucleus injury. In some individuals, extensive white matter injury correlates with more significant overall cortical atrophy and increased risk for dementia, as shown in image (B).
The presence of lesions suggestive of ischemia or lacunar infarction on MRI or tomography should always be correlated with clinical examination and neuropsychological examination findings. On the other hand, the absence of vascular lesions on CT or MRI indicates the low probability of a vascular etiology of dementia. The operational guidelines of the NINDS-AIREN - Association Internationale pour la Recherche et l’Enseignement en Neurosciences - are used to understand the radiological aspects of VCI, being fundamental for the diagnosis of probable VaD [33, 37].
Subcortical vascular lesions result from small vessel disease and can be identified at MRI as pointy, diffuse, or localized areas, hyperintense in FLAIR and T2-weighted sequences [53]. Some authors distinguished their locations in periventricular and subcortical. Several studies in neuroimaging have adopted volumetric techniques for the measurement of neuroimaging volume. However, visual methods have wide use in the clinical routine, giving their straightforward interpretation an advantage. One is the use of the Fazekas scale (Figure 1), ranging from 0 to 3. Recommendations for neuroimaging characterization of SIVD also include the analyses of cerebral microbleeds and perivascular spaces [39, 50, 53].
Diffusion tensor or diffusion tensor imaging (DTI) is a structural resonance technique based on the displacement of water molecules along axon fibers. DTI can be very useful as a biological marker of loss of axonal integrity and is a promising technique in the early diagnosis of neuronal disconnections in several neuropsychiatric conditions, including VAD. Studies investigating brain vascular-related changes have shown the importance of evaluating specific brain regions, such as fornix, cingulate, and hippocampus; another focus of clinical interest of DTI has been the investigation between vascular and degenerative factors in dementia, especially the role of ischemic vascular lesions in conversion to AD [54]. In addition, axonal lesions may be associated with increased blood pressure, even in the absence of a diagnosis of hypertension [55].
Neurovascular evaluation includes several complementary tests, such as ultrasonography (USG) of cervical carotid and vertebral arteries and CT or RM angiography of the carotid and vertebral arteries. These tests investigate vascular pathologies, e.g., atheromatous plaques and changes in cerebral blood flow. In cases where detailed visualization of the cervical and intracranial arterial tree is necessary, such as suspected aneurysm, MRI or CT angiography may be used.
The use of single-photon emission tomography (SPECT) seems relevant in the differential diagnosis with VAD and, in typical Binswanger-type VaD, the finding of diffuse hypoperfusion. Concerning positron emission tomography (PET), different patterns of metabolism reduction are usually associated with VAD; these include diffuse hypometabolism in SIVD, frontal or multifocal, as in the case of lacunar or multiple infarctions. The use of PET or SPECT is recommended in the investigation of atypical cases, in which there are doubt diagnoses after clinical examination and structural neuroimaging.
The comorbidity of VCI and mood disturbances, particularly affective symptoms, led to the proposition of a hypothesis known as “vascular depression” [56]. Statistically, anxiety (70%) and depression (20%) are the most frequent symptoms found in VCI [57]. Studies estimate that the prevalence of depression in VaD is 13.1% in community samples and 21.4% in-hospital samples [57]. The high prevalence of depression in VAD (8–66%) and the frequent occurrence of visual hallucinations, especially in multi-infarct dementia, were observed compared to AD [58]. Conversely, mania (1%), psychotic symptoms are less common but have frequency similar to that encountered in AD.
The neuropathological mechanisms associated with behavioral alterations result from frontal and or subcortical involvement in different circuits and may reflect diffuse lesions or strategic anatomical structures. Behavioral changes may be accompanied by cognitive symptoms, such as concentration difficulties, slowing cognitive processing, and executive dysfunction.
Considering the absence of specific treatment of CCV, the available therapeutic strategies comprise, above all, aspects of prevention [45, 59]. Therefore, the binomial control of risk factors—promotion of good health constitutes the main objective from the individual, epidemiological and public health point of view. Successful prevention depends on the control and modification of risk factors and the effectiveness of protective factors, such as adequate lifestyle (including diet, physical activity, among others) [46]. It should be emphasized that prevention measures should be maintained from the brain-at-risk to the various CCV symptomatic presentations.
Neuropsychiatric symptoms are seen in all phases of CCV, most marked in the more advanced ones. Its treatment is necessary, considering its interference in other areas of performance and the quality of life of patients and family members. Treatment can be established after the correct definition of the problem, away from personal environmental factors of discomfort, and the differential diagnosis (e.g., delirium [infectious, metabolic, or drug-induced confusional states]). Initially, non-pharmacological strategies (environmental, behavioral, psychological, should be used) and pharmacological treatment, when indicated, should be safe and effective, minimizing cardiovascular side effects to avoid additional vascular injury [60].
The treatment of VaD can be didactically divided into pharmacological and non-pharmacological strategies. The first includes preventive measures based on epidemiological findings, e.g., the effective control of vascular risk factors [61]. Therefore, there is consensus among the authors regarding the need to treat hypertension, dyslipidemia, diabetes, and other associated factors, although the effect size of preventive, therapeutic interventions for each risk factor remains disputable [6]. Nevertheless, studies suggest that effective control of hypertension results in a decrease of up to 34% in the incidence of VaD.
Both hypertension and diabetes and have been related to the higher incidence of VCI. Blood glucose control should be moderate (glycated hemoglobin between 7 and 7.9%); however, scarce evidence for a specific class of antihypertensive drugs remains [6, 62]. Patients with heart disease, e.g., atrial fibrillation, should be carefully monitored for appropriate anticoagulation levels. Smoking cessation should be stimulated regardless of age group.
Evidence from animal studies points to the benefits of physical activity in angiogenesis, brain, and neurogenesis. Population studies have confirmed these findings by demonstrating a favorable role of physical activity in the lowest conversion rate for dementia and the most beneficial evolution [6]. However, the benefits seem less robust for VaD than for AD [6].
The higher intake of polyunsaturated acids and omega 3, fibers, bowls of cereal, the moderate consumption of milk and its derivatives, meats, and saturated fatty acids have been associated with reducing the conversion of MCI and AD. Moderate alcohol use in about one or two drinks (<30 g/d) and adequate weight control also had a protective effect on VAD development. The mechanisms underlying this effect would be reducing LDL, increased HDL, reducing alcohol consumption, insulin resistance and blood pressure, reducing platelet aggregation and serum fibrinogen and homocysteine levels and inflammatory markers.
Neuropsychological rehabilitation may have a role in the treatment of cognitive deficits and neuropsychiatric symptoms in VCI. Individual or group family support can also be valuable in the rehabilitation process, providing caretakers with information about the disease and prognosis and offering emotional support for coping [63]. Most studies with cognitive intervention, however, showed reduced efficacy in improving cognitive function with cognitive rehabilitation. Some findings highlight the lack of evidence due to methodological difficulties, such as the duration of the intervention, the instruments used as the control of confounding variables (medical comorbidities and psychiatric alterations).
The frequent overlap of pathological mechanisms between VaD and AD suggests that the use of acetylcholinesterase inhibitors may be useful in patients with vascular brain disease. The use of donepezil showed good tolerability and may improve cognitive and functional status. Rivastigmine has shown to be effective on cognition, although with an effect size proportionally lower than donepezil [62].
The use of cholinesterase inhibitors and the N-methyl-d-aspartate (NMDA) receptor modulators in patients with VaD and VCI has been controversial, although the benefits seem more evident with specific groups, e.g., individuals with the subcortical disease. Memantine, an NMDA antagonist, would act on the toxic action caused by glutamatergic overactivation, putatively exhibiting brain neuroprotective properties. There is also a need for further evidence demonstrating the benefits of this medication in VAD, but some specialists point to a possible improvement in subcortical conditions [62].
Pharmacological treatment of behavioral alterations aims at symptomatic remission or stabilization. Antidepressants may be indicated in moderate or severe depressive symptoms or when monotherapy with acetylcholinesterase inhibitors has no effective response. Serotonin reuptake inhibitors (SSRI), venlafaxine, mirtazapine, and trazodone are usually regarded as the safest and most well-tolerated options.
The use of trazodone or anticonvulsant has been used in maniform symptoms, agitation, or aggressive behavior. Carbamazepine shows evidence of success in reducing agitation. Newer drugs such as gabapentin may still show effectiveness in these conditions. Atypical antipsychotics may also be an alternative in agitation, and use should be restricted to the acute period. Risperidone and olanzapine are drugs with better tolerability. However, the occurrence of sedation and risk and falls and the evidence of increased incidence of drug-related vascular events demand thorough dosage monitoring, with the risks and benefits being weighed on a case-by-case basis.
The use of ginkgo Biloba, nimodipine (potassium channel blocker), and antioxidant agents requires further scientific evidence.
Regarding surgical interventions, studies have sought evidence of improvement in cognitive function after carotid revascularization, but the results are still inconclusive. Conversely, studies have pointed to cognitive improvement after carotid stent implantation against embolism, but these results require confirmation with long-term follow-up of patients.
This chapter provided a concise review of epidemiological, diagnostic, and clinical aspects of vascular brain diseases. For most countries, vascular brain disease is a significant cause of dementia, and their presence, alone or associated with degenerative conditions, increases the risk of conversion to progressive cognitive decline. Neuropsychiatric manifestations vary according to the affected brain territory and disrupted neuronal circuits; behavioral disturbances include, for instance, mood, psychomotor, or thought disorders; cognitive deficits involve memory, attention, language, and other alterations, depending on the extension and localization of the lesions. Early diagnosis may have a decisive impact on clinical evolution and should guide health policies involving the old age population. Treatment involves a wide range of strategies, including controlling cardiovascular and metabolic risk factors and adopting a healthy lifestyle. Pharmacological treatment may include cholinesterase inhibitors and NMDA modulators, which aim to stabilize symptoms and, although not officially approved, are recommended depending on the stages of dementia. The safety and effectiveness of antipsychotics and antidepressants, particularly in managing agitation, psychosis, and depression, require further studies.
The authors declare no conflict of interests.
AD | Alzheimer’s dementia |
TIA | transient ischemic attack |
CADASIL | cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy |
CVD | cerebrovascular disorders |
DTI | diffusion tensor imaging |
HIS | Hachinski ischemic scale |
HIE | hemorrhagic ischemic events |
ICD | international classification of diseases |
MCI | mild cognitive impairment |
MD | mixed dementia |
NINDS-AIREN | |
NMDA | N-methyl-d-aspartate |
VaD | vascular dementia |
VCI | vascular cognitive impairment |
VCIND | vascular cognitive impairment not dementia |
VMCI | mild cognitive impairment of vascular origin |
VRF | vascular risk factors |
SIVD | subcortical vascular ischemic disease |
SPECT | single-photon emission tomography |
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\n\nIf the manuscript is formally accepted after peer review you will receive a formal Notice of Acceptance, and a price quote.
\n\nThe Open Access Publishing Fee of your IntechOpen Compacts, Monograph or Edited Book depends on the volume of the publication and includes: project management, editorial and peer review services, technical editing, language copyediting, cover design and book layout, book promotion and ISBN assignment.
\n\nWe will send you your price quote and after it has been accepted (by both the author and the publisher), both parties will sign a Statement of Work binding them to adhere to the agreed upon terms.
\n\nAt this step you will also be asked to accept the Copyright Agreement.
\n\n5. LANGUAGE COPYEDITING, TECHNICAL EDITING AND TYPESET PROOF
\n\nYour manuscript will be sent to Straive, a leader in content solution services, for language copyediting. You will then receive a typeset proof formatted in XML and available online in HTML and PDF to proofread and check for completeness. The first typeset proof of your manuscript is usually available 10 days after its original submission.
\n\nAfter we receive your proof corrections and a final typeset of the manuscript is approved, your manuscript is sent to our in house DTP department for technical formatting and online publication preparation.
\n\nAdditionally, you will be asked to provide a profile picture (face or chest-up portrait photograph) and a short summary of the book which is required for the book cover design.
\n\n6. INVOICE PAYMENT
\n\nThe invoice is generally paid by the author, the author’s institution or funder. The payment can be made by credit card from your Author Panel (one will be assigned to you at the beginning of the project), or via bank transfer as indicated on the invoice. We currently accept the following payment options:
\n\nIntechOpen will help you complete your payment safely and securely, keeping your personal, professional and financial information safe.
\n\n7. ONLINE PUBLICATION, PRINT AND DELIVERY OF THE BOOK
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\n\nIf you feel that IntechOpen Compacts, Monographs or Edited Books are the right publishing format for your work, please fill out the publishing proposal form. For any specific queries related to the publishing process, or IntechOpen Compacts, Monographs & Edited Books in general, please contact us at book.department@intechopen.com
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Since the protein aggregation process in humans is a slow process, early determination of the patients that will develop neurodegenerative diseases later in life is critical in terms of starting effective treatment, which will reduce the expensive health care. In this chapter, I will discuss the nature of protein aggregation of signature proteins and the status of protein proteolytic systems such as proteasome and autophagosome in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Huntington’s disease, and prion disease under the light of recent studies including our new findings.",book:{id:"7480",slug:"neurochemical-basis-of-brain-function-and-dysfunction",title:"Neurochemical Basis of Brain Function and Dysfunction",fullTitle:"Neurochemical Basis of Brain Function and Dysfunction"},signatures:"Abdulbaki Agbas",authors:[{id:"250609",title:"Prof.",name:"Abdulbaki",middleName:null,surname:"Agbas",slug:"abdulbaki-agbas",fullName:"Abdulbaki Agbas"}]},{id:"62431",doi:"10.5772/intechopen.79266",title:"The United Chemicals of Cannabis: Beneficial Effects of Cannabis Phytochemicals on the Brain and Cognition",slug:"the-united-chemicals-of-cannabis-beneficial-effects-of-cannabis-phytochemicals-on-the-brain-and-cogn",totalDownloads:1813,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"‘Medicinal cannabis’ can be defined as pharmaceutical grade cannabis-based products used for the treatment of illness. Beneficial treatment effects of cannabidiol (CBD), a major non-intoxicating compound isolated from the cannabis plant, have been shown in multiple states of cognitive impairment, including neurodegenerative (Alzheimer’s, Huntington’s and Parkinson’s disease), neuroinflammatory (sepsis-induced encephalopathy) and neurological disorders (ischemic brain injury). CBD can also treat some of the symptoms of schizophrenia, including cognitive deficits (impairments in learning and memory), which is a major symptom domain of the illness that is largely resistant to existing antipsychotic medications. However, empirical evidence suggests the presence of an ‘entourage effect’ in cannabis; that is, observations that medicinal cannabis seems to work better in some instances when administered as a whole-plant extract. While scientific evidence highlights isolated CBD as a strong candidate for treating cognitive impairment, the entourage effect suggests that the co-operation of other plant molecules could provide further benefits. This chapter explores the scientific evidence surrounding the benefits of CBD and other specific key phytochemicals in cannabis: linalool, α-pinene, β-caryophyllene, flavonoids and anthocyanin, on brain health and cognition.",book:{id:"7040",slug:"recent-advances-in-cannabinoid-research",title:"Recent Advances in Cannabinoid Research",fullTitle:"Recent Advances in Cannabinoid Research"},signatures:"Katrina Weston-Green",authors:null},{id:"55884",doi:"10.5772/intechopen.69111",title:"Production and Function of Serotonin in Cardiac Cells",slug:"production-and-function-of-serotonin-in-cardiac-cells",totalDownloads:1567,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"Serotonin [5-hydroxy-tryptamine (5-HT)] exerts a number of effects in the mammalian heart: increase in heart rate, increase in force of contraction, fibrosis of cardiac valves, coronary constriction, arrhythmias and thrombosis. These effects are, in part, mediated by 5-HT-receptors, in part, directly by 5-HT action on intracellular proteins. In the beginning, 5-HT was thought to be only produced in the gut and then transported into the heart via platelets, because platelets can take up 5-HT in the gut and enter the capillaries and thus the mammalian heart. 5-HT is to a large extent metabolized in the liver and excreted via the urine. Here, we will also overview data that argue for additional pathways, namely production and degradation of 5-HT in the cells of the heart itself.",book:{id:"5780",slug:"serotonin-a-chemical-messenger-between-all-types-of-living-cells",title:"Serotonin",fullTitle:"Serotonin - A Chemical Messenger Between All Types of Living Cells"},signatures:"Joachim Neumann, Britt Hofmann and Ulrich Gergs",authors:[{id:"198376",title:"Prof.",name:"Joachim",middleName:null,surname:"Neumann",slug:"joachim-neumann",fullName:"Joachim Neumann"},{id:"205353",title:"Dr.",name:"Britt",middleName:null,surname:"Hofmann",slug:"britt-hofmann",fullName:"Britt Hofmann"},{id:"205354",title:"Dr.",name:"Ulrich",middleName:null,surname:"Gergs",slug:"ulrich-gergs",fullName:"Ulrich Gergs"}]}],mostDownloadedChaptersLast30Days:[{id:"62431",title:"The United Chemicals of Cannabis: Beneficial Effects of Cannabis Phytochemicals on the Brain and Cognition",slug:"the-united-chemicals-of-cannabis-beneficial-effects-of-cannabis-phytochemicals-on-the-brain-and-cogn",totalDownloads:1813,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"‘Medicinal cannabis’ can be defined as pharmaceutical grade cannabis-based products used for the treatment of illness. Beneficial treatment effects of cannabidiol (CBD), a major non-intoxicating compound isolated from the cannabis plant, have been shown in multiple states of cognitive impairment, including neurodegenerative (Alzheimer’s, Huntington’s and Parkinson’s disease), neuroinflammatory (sepsis-induced encephalopathy) and neurological disorders (ischemic brain injury). CBD can also treat some of the symptoms of schizophrenia, including cognitive deficits (impairments in learning and memory), which is a major symptom domain of the illness that is largely resistant to existing antipsychotic medications. However, empirical evidence suggests the presence of an ‘entourage effect’ in cannabis; that is, observations that medicinal cannabis seems to work better in some instances when administered as a whole-plant extract. While scientific evidence highlights isolated CBD as a strong candidate for treating cognitive impairment, the entourage effect suggests that the co-operation of other plant molecules could provide further benefits. This chapter explores the scientific evidence surrounding the benefits of CBD and other specific key phytochemicals in cannabis: linalool, α-pinene, β-caryophyllene, flavonoids and anthocyanin, on brain health and cognition.",book:{id:"7040",slug:"recent-advances-in-cannabinoid-research",title:"Recent Advances in Cannabinoid Research",fullTitle:"Recent Advances in Cannabinoid Research"},signatures:"Katrina Weston-Green",authors:null},{id:"68776",title:"Introductory Chapter: The Chemical Basis of Neural Function and Dysfunction",slug:"introductory-chapter-the-chemical-basis-of-neural-function-and-dysfunction",totalDownloads:1110,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"7480",slug:"neurochemical-basis-of-brain-function-and-dysfunction",title:"Neurochemical Basis of Brain Function and Dysfunction",fullTitle:"Neurochemical Basis of Brain Function and Dysfunction"},signatures:"Thomas Heinbockel and Antonei B. Csoka",authors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",slug:"thomas-heinbockel",fullName:"Thomas Heinbockel"},{id:"245650",title:"Dr.",name:"Antonei B.",middleName:null,surname:"Csoka",slug:"antonei-b.-csoka",fullName:"Antonei B. Csoka"}]},{id:"68712",title:"Synaptic Transmission and Amino Acid Neurotransmitters",slug:"synaptic-transmission-and-amino-acid-neurotransmitters",totalDownloads:1361,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"Amino acids are the most abundant neurotransmitters in the brain. Neurotransmitters are synthesized and stored in presynaptic terminals, released from terminals upon stimulation with specific receptors on the postsynaptic cells. Chemical and electrical synapses are specialized biological structures found in the nervous system; they connect neurons together and transmit signals across the neurons. The process of synaptic transmission generates or inhibits electrical impulses in a network of neurons for the processing of information. Glutamate is the primary excitatory neurotransmitter in the brain, while GABA is the principal inhibitory neurotransmitter. The balance of glutamatergic and GABAergic tone is crucial to normal neurologic function. Through synaptic transmission, this information is communicated from the presynaptic cell to the postsynaptic cell. Amino acid neurotransmitters primarily glutamic acid, GABA, aspartic acid, and glycine are single amino acid residues released from presynaptic nerve terminals in response to an action potential and cross the synaptic cleft to bind with specific receptor on the postsynaptic membrane. The integral role of amino acid neurotransmitters is important on the normal functioning of the brain. The presynaptic and postsynaptic events in chemical synapses are subject to use dependent and highly regulated as per the changes in synaptic neurotransmitter release and function.",book:{id:"7480",slug:"neurochemical-basis-of-brain-function-and-dysfunction",title:"Neurochemical Basis of Brain Function and Dysfunction",fullTitle:"Neurochemical Basis of Brain Function and Dysfunction"},signatures:"Manorama Patri",authors:[{id:"196763",title:"Dr.",name:"Manorama",middleName:null,surname:"Patri",slug:"manorama-patri",fullName:"Manorama Patri"}]},{id:"46296",title:"Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity",slug:"physiological-role-of-amyloid-beta-in-neural-cells-the-cellular-trophic-activity",totalDownloads:5908,totalCrossrefCites:19,totalDimensionsCites:32,abstract:null,book:{id:"3846",slug:"neurochemistry",title:"Neurochemistry",fullTitle:"Neurochemistry"},signatures:"M. del C. Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. 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