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Centre for Infection, Immunity and Disease Mechanisms, Brunel University, London, United Kingdom
Domenico Marco Bonifati
Unit of Neurology, Department of Neurosciences, Santa Chiara Hospital, Trento, Italy
Uday Kishore
Centre for Infection, Immunity and Disease Mechanisms, Brunel University, London, United Kingdom
*Address all correspondence to: abhishek.shastri@brunel.ac.uk and domenicomarco.bonifati@apss.tn.it
1. Introduction
The non-Alzheimer dementias (NAD) are a group of disorders that account for approximately 30 to 40 per cent of dementias worldwide [1-3]. Some of the common types of NAD are listed in Table 1.
The term vascular dementia (VaD) deals with cognitive impairment affecting daily activities required for living of vascular origin (ischemia, haemorrhage). However, VaD as a concept and disease entity is undergoing regular transformation. The term ‘vascular cognitive impairment’ (VCI) introduced in 1995 [4] is used to include any cognitive impairment from cerebrovascular disease (CVD) except major stroke. It was then proposed that the term VCI should include all forms of cognitive impairment associated with CVD [5] (Table 2). This term would include not only VaD but also mild cognitive impairment (MCI) with no dementia and dementia of mixed origin (Alzheimer’s and vascular dementia) (see [6]). It has been argued that this classification does not fit the purpose of clinical differentiation and that this term should be restricted to MCI without dementia due to vascular cause [7]. However, some scholars are of the opinion that VCI is a research terminology and that clinicians should identify the condition and deal with the associated risk factors thereby avoiding progression to VaD [8].
The diagnostic criteria that characterise cognitive syndromes associated with vascular disease are usually based on two factors: demonstration of presence of a cognitive disorder by neuropsychological testing and history of clinical stroke or presence of vascular disease by neuroimaging that suggests a link between the cognitive disorder and vascular disease. The term VCI is not used for patients who have an active diagnosis of drug or alcohol dependence or for patients with delirium [9].
2.1. Epidemiology
VaD is considered to be the second most prevalent type of dementia worldwide accounting for about 15 to 20 % of the dementia cases [10]. Prevalence of VaD in Japan has been reported to be as high as 47 % [11]. 16 % of all cases of late-onset dementia (65 years or after) [12] and 18 % of all cases of early-onset dementia (below 65 years) [13] was found to be VaD. However, it must be kept in mind that establishing the exact epidemiology of VaD is not an easy task mainly due to difficulty in diagnosing clinically [14] and overlap of AD neuropathology (see [15]).
Some of the risk factors for developing VaD are hypertension [16] and metabolic factors like diabetes and obesity. Males are considered to be at a significantly higher risk of developing VaD [17]. The incidence rate of VaD was found to be two times higher than Alzheimer’s disease for males in Japan [18]. The risk factors have been classified [19] and are listed in Table 3. Some of the protective factors found in the Canadian Study of Health and Aging include eating shellfish and regular exercise for women [20]. Antioxidants, which include vitamin E and C and also intake of fatty fish have been found to be protective against VCI [21].
a. Vascular dementia • Vascular dementia of acute onset (post-stroke) • Multi-infarct dementia • Subcortical vascular dementia (Binswanger’s disease) • Mixed cortical and subcortical vascular dementia • Other vascular dementia (CADASIL, vasculitis, post-cardiac arrest) b. Dementia with Lewy Bodies c. Frontotemporal dementia d. Dementia in other diseases • Pick’s disease • Creutzfeldt-Jakob disease • Huntington’s disease • Parkinson’s disease • Human immunodeficiency virus (HIV) disease e. Treatable or reversible dementias • Normal pressure hydrocephalus • Alcohol-related • Neoplasia (glioma, meningioma, secondaries) • Vitamin deficiencies (B12, folate, thiamine, nicotinic acid) • Metabolic and endocrine (liver disease, hypothyroidism)
1. Demographic Age Male sex Lower educational level 2. Atherosclerosis Hypertension Cigarette smoking Myocardial infarction Diabetes mellitus Hyperlipidemia 3. Genetic CADASIL Apolipoprotein E 4. Stroke-related Volume of cerebral tissue loss Bilateral cerebral infarction Strategic infarction (thalamic, angular gyrus) White matter disease
Table 3.
Risk factors for vascular dementia according to reference [18]
2.2. Clinical features and pathophysiology
Firstly, to diagnose dementia, there should be a decline in memory and a decline in at least two cognitive skills such as orientation, social behaviour, verbal skills, attention, motor control, praxis, emotional control and executive functions (goal-directed behaviour and problem-solving skills). In VaD, the onset may be sudden or gradual, with stepwise progression. Since vascular component is involved, there may be focal neurological deficits such as hemiparesis or swallowing disturbances and dysarthria (pseudobulbar lesion symptoms). A history of transient ischaemic attacks is common. Depending on the site of the lesion, features such as motor aphasia, dyspraxia (due to left anterior cerebral artery ischemia) or psychosis (right middle cerebral artery) or amnesia and visual disturbances (posterior cerebral artery) may be seen. Other important associated features include gait disturbance which may be associated with a history of unsteadiness as well as frequent falls. It is vital to distinguish dementia of vascular origin from degenerative form of dementia. This is because VaD, when diagnosed at an early stage provides for chances to prevent or delay progression. Thus, treatment strategies may vary. For this purpose, clinicians use a scoring system called Hachinski ischaemic score [22]. A score of above six signifies dementia due to vascular cause. Some of the clinical criteria developed to assist in diagnosing VaD include State of California Alzheimer Disease Diagnostic and Treatment Centers (ADDTC) criteria [23], International Classification of Diseases (ICD-10) criteria [24], National Institute of Neurological Disorders and Stroke (NINDS)-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria [25] and Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) criteria [26].
The most widely followed or accepted criteria for diagnosis of VaD is the NINDS-AIREN criteria. According to this, both clinical and radiological criteria must be fulfilled. Clinical criteria include presence of dementia and CVD as well as a relation between the two features i.e. dementia should develop after and within 3 months of the stroke. Radiological criteria are based on topography and severity of vascular lesions. There should be either a large vessel stroke or multiple lacunar infarcts in basal ganglia or white matter lesions in periventricular regions. Large vessel lesions should be present in dominant hemisphere or in both the hemispheres while white matter lesions must involve at least 25 % of the cerebral white matter. However it was found that the neuroimaging criteria listed above does not always differentiate between stroke patients with and without dementia [27]. Definite vascular dementia is diagnosed by fulfilling the above mentioned criteria with histopathological evidence from brain biopsy or autopsy. Absence of other causes of dementia must be ruled out.
2.2.1. Post-stroke dementia
Post-stroke dementia (PSD) is the type of VaD developing after a stroke. Among patients who have experienced a first stroke, the prevalence of poststroke dementia (PSD) varies in relation to the interval after stroke, definition of dementia, location and size of the infarct. This includes a large-vessel lesion or single strategic lesion (thalamus or midbrain) (Figure 1). The cause of stroke may be haemorrhagic, or ischemic. The rate of dementia in people with stroke was found to be two times respect people without stroke [28]. Increasing age is significantly associated with PSD [29,30]. The severity of cognitive decline after a stroke is associated with increased risk of PSD [31]. Long-term mortality is 2 to 6 times higher in patients with PSD after adjustment for demographic factors, associated cardiac diseases, stroke severity, and stroke recurrence (for review, see [32]). Silent cerebral infarcts, white matter changes, and global and medial temporal lobe atrophy are associated with increased risk of PSD [32]. Dementia is severe in lesions involving thalamus or midbrain. After stroke, recovery of patient involving both physical and cognitive functions is variable.
2.2.2. Multi-infarct dementia
As the name suggests, there are multiple strokes occurring in the same patient (Figure 2). Sometimes these may even go undetected and may be noticed only after a major stroke. This causes the characteristic step-wise progression of the disease where there may be deterioration in cognitive abilities but also there may be periods of stability or even improvement of the patient. The severity of dementia increases with each stroke. The type of vessel involved may be either large or small vessels or both. It is thought that the reason for multiple infarcts is due to underlying predisposing factors associated with VaD.
Figure 1.
Brain MRI scan (DWI sequences) of a 59 years old man presenting with an acute onset of confusion, ideative and motor slowness and apathy with memory loss. A marked cognitive and motor slowness and apathy remained after 15 days from onset. MRI scan showed ischemic lesions in the medial part of both thalami and in the midbrain (top of the basilar syndrome).
2.2.3. Binswanger’s disease
It is a type of subcortical ischaemic VaD. It is a progressive small vessel disease. Occlusion of small arteries (arterioles) leads to hypoperfusion and this in turn leads to white matter lacunes and necrosis [33]. Clinical features vary slightly where the patients develop a slowly progressing dementia. Brain imaging studies reveal increased white matter and periventricular lesions (Figure 3).
Figure 2.
Brain MRI (FLAIR sequences) of a 80 years old man with a multi-infarct progressive dementia with bulbar symptoms. Multiple cortical and subcortical infarct are seen together with periventricular white matter changes and corticola atrophy.
Figure 3.
White matter changes and periventricular lesions observed in a 82 years old man with loss of memory and slowly progressive cognitive impairment. Brain atrophy is also present (mixed dementia)
2.2.4. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
CADASIL is a familial form of vascular dementia. It is associated with migraine and is a subcortical ischaemic type of dementia. It is due to mutation in the NOTCH3 gene on chromosome 19. It is the most common genetic form of VaD. The disease has an autosomal dominant type of inheritance. From the pathological point of view vascular lesions occur not only in vessels of the brain but also other organs. Hence, it can be diagnosed by skin biopsy and confirmed by immunohistochemistry with NOTCH3 monoclonal antibody [34]. Brain imaging shows white matter lesions of necrosis and lacunae. A recessive form has also been described and mutations in the HTRA1 gene identified [35,36].
2.3. Neuropathology
The types of lesions seen in VaD are mainly infarctions. The infarctions may be present in the cortex and subcortical regions (complete infarctions) as well as the white matter and basal ganglia (lacunar infarctions). Cerebral amyloid angiopathy may be observed. Atrophy and sclerosis of hippocampus are also common [37]. A study was conducted on 135 post-mortem brains with dementia to conceptualize the natural history of cerebrovascular lesions (CVL) and operationalize it into a cerebrovascular staging system [38]. The authors rated the following CVL; in the frontal and temporal lobes: arteriosclerosis, amyloid angiopathy, perivascular hemosiderin leakage, perivascular spaces dilatation in deep and juxtacortical white matter, myelin loss and cortical infarcts; in the hippocampus: neuronal loss, perivascular spaces dilatation and presence of micro- and large infarcts; in the basal ganglia: arteriosclerosis, perivascular spaces dilatation, density of micro- and large infarcts, either lacunar or territorial.
2.4. Management
2.4.1. Investigations
Routine blood investigations and biochemistry including lipid and glucose levels as well as liver enzymes must be done in order to rule out treatable causes of dementia and identify risk factors such as hyperlipidemia and diabetes. The Mini-Mental State Examination is a brief but good way of screening for dementia. Executive function may be tested by Clock-Drawing Task. A proper history from the patient and/or informant must be obtained and should include history for unprovoked falls, TIA and urinary incontinence also. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are useful investigations to check for both large and small infarcts and white matter lesions. Other imaging techniques like Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) may be done to assess blood flow. Population MRI studies have revealed high prevalence of overt small-vessel disease in the elderly population (23 % for silent lacunes and 95 % for incidental hyperintensities). These lesions are associated with an increased risk for stroke and dementia [39]. A thorough and complete neurological examination must be done to confirm signs of stroke. It is extremely important to conduct a good cardiovascular examination including measuring blood pressure and examining for presence of murmurs. Electrocardiogram to look for presence of fibrillation is essential.
2.4.2. Treatment
Since there are several risk factors associated with developing VaD, it is important to treat them or keep them in check. In people at risk for VCI, smoking cessation is mandatory. Lifestyle modification such as eating a low-fat diet, moderation in alcohol intake and regular exercise are reasonably effective. Hypertension, hyperglycemia and hypercholesterolaemia must be treated. Antiplatelet therapy is used and is effective in preventing further strokes. Primary prevention with antihypertensive drugs perindopril and indapamide has been shown to be effective in reducing risk of dementia and cognitive decline in patients with recurrent stroke [40]. Treatment of VaD is usually symptomatic. No specific drug has yet been recommended. Cholinesterase inhibitors (ChEI) such as donepezil have been found to be beneficial in improving cognition [41] but other ChEI such as galantamine[42] and rivastigmine [43] have been found to be ineffective. N-methyl-D-aspartate antagonist like memantine has been tried in trials but was also found to be ineffective [44].
2.5. Prognosis
The prognosis of VaD is generally poor. Most patients die within few years from onset. Death may be due to CVD or complications of dementia. Since there is no specific treatment recommended, it is very important to diagnose the disease at an early stage and stop it from progressing further. Preventive measures are also vital.
Dementia with Lewy Bodies (DLB) is a degenerative type of dementia (like AD). It is the second most common type of degenerative dementia (after AD). Lewy Bodies are inclusion bodies present in the cytoplasm containing a protein called ubiquitin. The first cases of DLB with cortical involvement were reported in 1961 [45]. The Lewy Body was seen in autopsy by neuropathological staining only as far as 1989 [46]. Over the years, DLB has been given several terminologies, namely diffuse Lewy body Disease [47], Lewy body dementia [48], Lewy body variant of AD [49], senile dementia of Lewy body type [50] and dementia associated with cortical Lewy bodies [51].
3.1. Epidemiology
The prevalence of DLB is about 0.1 to 5 % in the general population and about 10 to 20 % of all dementia cases [52-54]. The incidence is about 0.1 % a year in the general population and about 3 % a year of all new dementia diagnosed cases [55]. A French cohort study found that the incidence of DLB increases with age [56].
3.2. Clinical features and pathophysiology
The main feature is the presence of dementia which means impairment of cognition affecting normal day to day and social activities. Guidelines [57] suggest the core features as being fluctuation in level of cognition, detailed visual hallucinations that are recurrent and parkinsonism that is spontaneous. Any two of these core features indicate probable DLB while the presence of only one of the core features indicates possible DLB. Other psychiatric features may include depression, anxiety or apathy. There may also be a history of repeated falls given by the carers. Another interesting feature is the presence of Rapid Eye Movement sleep behaviour disorder (RBD) [58, 59]. RBD is a sleep disorder and is characterized by loss of muscle atonia during rapid eye movement as well as movement of limbs, with or without vocalization and dreaming. Carers often give a history that it is as though the patient is acting out his or her dreams. A recent study [60] found that inclusion of RBD as a core feature may help improve diagnosis of DLB.
On pathological examination, LB contain ubiquitin which is examined by immunohistochemistry. Increased presence of LB in the parahippocampus has been linked to increase in the severity of dementia [61]. DLB patholgy has been shown to be related to plaques in hippocampus and amygdala [62]. Another biomarker for diagnosis is α-synuclein (AS) immunohistochemistry [63]. Genetic mutation of AS has also been associated with DLB [64]. Diagnosis with AS staining was found to be more sensitive and more specific than ubiquitin staining [65]. Presence of LB in the temporal lobe has been shown to be related to visual hallucinations [66].
3.3. Management
3.3.1. Investigations
Clinically, dementia must be diagnosed. Other neuropsychiatric features such as depression, hallucinations and sleep disturbances must be identified. Proper history from carer or family member must be obtained. A complete psychiatric and neurological evaluation must be carried out. There are no specific diagnostic tests. MRI may show preservation of medial temporal lobe [67] or reduced amygdala volume [62]. SPECT may show hypoperfusion in occipital lobe [68]. Using SPECT with dopamine transporter imaging is turning out to be promising [69,70]. Imaging and findings of global amyloid deposition may also give a clue in diagnosis of LBD [71].
3.3.2. Treatment
Drugs used in treatment include levodopa viz. usually used to treat Parkinson’s disease. A one year follow-up study has shown it to be acutely effective [72] but its use is debatable as it also lead to adverse effects most notably being hallucinations [73]. Another promising drug is memantine which was also found to be well tolerated [74]. A Cochrane review found cholinesterase inhibitors to be not useful in patients with DLB [75]. Other measures include education of carers and also reality orientation of patients.
3.4. Prognosis
The prognosis in DLB can be variable. Initial health and well-being may play a role in deciding the prognosis. When compared to AD, the prognosis has been found to be similar [76] as well as more severe [77]. No single factor have been identified that may dictate the outcome of disease progression [78].
Frontotemporal dementia (FTD) is considered to be the second most common type of early-onset (before the age of 65) dementia. There is pathological involvement of frontal and temporal lobes of the brain. FTD consists of a behavioural variant (bvFTD) and a language variant. The language variant can be further divided into semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Overlap of FTD with motor neuron disease (MND) is also seen clinically, pathologically and genetically [79]. The whole clinico-pathological spectrum is often referred to as frontotemporal lobar degeneration.
4.1. Epidemiology
The prevalence of FTD was found to be about 15 in 100,000 in UK involving age groups 45-64 years [80] while in the Netherlands it was found to be 9.4 per 100,000 in the age group 60-69 years [81]. The prevalence of early-onset AD and FTD was (be consistent between past and present verbs) found to be similar [80,82]. The incidence was found to be about 3.5 cases per 100000 person-years [83]. Average age of onset is around 50-60 years [80,81].
4.2. Clinical Features and pathophysiology
The core features are an insidious onset, decline in personal and social conduct as well as early emotional blunting and loss of insight [84]. The most common presenting symptoms are then changes in behaviour. Decrease in cognitive functions involving executive functions and speech is also observed. bvFTD is the most common of the subtypes [85] and is considered to be the most typical of FTD. It is associated with degeneration of frontal and temporal lobes [86] Other important features include behavioural disinhibition, apathy and loss of empathy [87]. SD is characterised by loss of ability to name and recognise words, objects and faces. It is associated with atrophy of left temporal lobe [88]. However, at least initially, speech in SD may be unhampered, fluent and grammatically correct [89]. In PNFA, speech is hampered and is grammatically incorrect but usually comprehension is preserved. This is associated with problems in language expression [89] and also with left temporal lobe atrophy and Broca’s area degeneration [84,90]. FTD associated with MND has similar clinical presentations involving areas of language, memory and behavioural changes[91]. Genetic studies involving families where some members have FTD and others have MND have shown a repeat of hexanucleotide sequence GGGGCC in chromosome 9 open reading frame 72 region (C9ORF72) [92,93].
FTLD shows atrophy or degeneration of frontal and/or temporal lobes along with microvacuolation and neuronal loss in the cerebral cortex [94]. By the use of immunohistochemistry, FTLD is associated with the accumulation of microtubule-associated protein tau and transactive response DNA-binding protein 43 (TDP-43). It can also be divided into two types (1) FTLD with tau-positive inclusions (FLTD-tau) and (2) FTLD with ubiquitin-positive and TDP-43-positive but tau-negative inclusions (FLTD-TDP) [95]. FLTD-tau mainly present as PNFA and overlap with Pick’s disease while FLTD-TDP present mainly as SD and is associated with MND. Patients with bvFTD can show either of the two types of pathology [96,97]. Apart from TDP-43 involvement in MND, another protein called fused in sarcoma (FUS) is also associated with familial cases of dementia and MND [98].
4.3. Management
4.3.1. Investigations
MRI is the most useful investigation. Features of lobar atrophy may be observed. In bvFTD, there is involvement of frontal, temporal, cortical and subcortical areas (Figure 4). Hypoperfusion of these areas is also seen with SPECT and hypometabolism with PET. In the language variant, left temporal grey matter involvement is observed. Orbitofrontal cortex involvement is associated with behavioural changes in these patients. Also, cortical and subcortical hyoperfusion is found to be more marked on the left side [99]. A complete neuropsychological battery is necessary to fully characterise clinically these patients.
Figure 4.
MRI brain scan (FLAIR and T2 sequences) of a 75 old woman with progressive FTD with mainly behavioural disturbances showing frontal and temporal lobe atrophy along with minor periventricular hyperintensities. She had deficit in executive and attention functions, aggressive behaviour and obsessive-compulsive disorder.
4.3.2. Treatment
No known or effective treatment exists for FTD. Treatment is mainly supportive or palliative. Multi-disciplinary management involving psychiatrist, physician, clinical psychologist and specialist nurse may be an effective way to treat patients with FTD.
4.4. Prognosis
The prognosis varies and to some extent depends on the type of FTD. The severity of the disease is more and clinical progression is faster in bvFTD [100]. In the language variant, the disease progression is slow with mainly impairment of language component for several years [89].
Pick’s disease (PD) is a neurodegenerative disease. From the clinical point of view it overlaps with FTD but it is characterised by the presence of Pick bodies. These Pick bodies are argyrophilic, intraneuronal, cytoplasmic inclusions made up of three-repeat tau. Other features include circumscribed atrophy of frontal and temporal lobes, gliosis and loss of neurons [101] as it has seen in FTD. Clinically, patients present with symptoms similar to FTD such as those of bvFTD, PNFA and SD as mentioned previously. Therefore, it is difficult to distinguish FTD from PD clinically. Post-mortem clinical correlation studies have shown that PD is associated more closely with behavioural and language associated symptoms and not with motor disturbances [102]. The age of onset is around 45 to 65 years [103, 104]. There are no known risk factors associated with PD. ‘Knife-edge’ atrophy is observed pathologically in the cortex which implies sharp, circumscribed degeneration (also referred to as ‘dried walnut’ appearance) [105]. There may also be the presence of swollen, ballooned neurons in the cortex called as Pick cells although they are not always present. No specific treatment is available at present for PD.
5.2. Dementia in Creutzfeldt-Jakob disease
Creutzfeldt-Jakob disease (CJD) is a subacute fatal neurodegenerative disease. It is the most common of the prion diseases to affect humans. Prion proteins are infectious-like agents that cause diseases termed as transmissible spongiform encephalopathies. Prion proteins are found normally in the cells of central nervous system and immune system [106]. However, a misfolded form of this protein is considered to be pathologic. CJD occurs as sporadic, genetic, iatrogenic or juvenile variant forms. Clinical features associated with CJD are a rapidly progressive encephalopathy with dementia, cerebellar ataxia and myoclonus [107]. It progresses to stupor and coma in few months. The sporadic form of CJD (sCJD) accounts for about 85 % of all CJD cases [108, 109]. The average age of onset is around 60 years. Median time to death is about 5 months and 85-90 % of patients die within 1 year of onset [110-112]. In the familial form, mutations in the gene PNRP that encodes the prion protein are seen. Autosomal dominant inheritance is observed. Disease progression is slower than sCJD. Iatrogenic form of CJD occurs accidently during surgical or medical procedures. In the juvenile variant form of CJD (vCJD), the age of onset is around 30 years. Other features include early psychiatric features (depression, anxiety, apathy), delay in dementia and duration of illness of more than 6 months [113,114]. Pathologically all cases of CJD have features of neuronal loss, spongiform changes (vacuolation in grey matter) and astrogliosis [107]. Pathological prion proteins can be observed via immunohistochemistry [113].
5.3. Dementia in Huntington’s disease
Huntington’s disease (HD) is a genetic cause of dementia. It is inherited as an autosomal-dominant trait. The mutation in the huntingtin gene (chromosome 4) producing the disease was identified in 1993 [115]. Mutant protein called huntingtin has an abnormal CAG repeats (at least 36) on the coding sequence of this gene. HD is characterised by chorea (involuntary, jerky movement of limbs spreading to all muscles of body), behavioural and psychiatric changes (mainly psychoses and depression) along with dementia. The onset is around middle age (about 40 years). Cognitive changes mainly slowing of intellectual capabilities and decline of executive functions occur and may sometimes be detected even before onset of motor symptoms [116, 117]. Dementia is progressive and increases as the course of the disease advances. Pathological features include neostriatal (caudate and putamen) atrophy in early stages of disease [118] and presence of intranuclear inclusions of mutant huntingtin in neurons of the striatum region of the brain [119]. Management includes genetic counselling, regular neurological and neuropsychiatric evaluation. Treatment is mainly symptomatic.
5.4. Dementia in Parkinson’s disease
Parkinson’s disease (PD) is a neurodegenerative disease mainly associated with motor symptoms. However, dementia develops in about 40 % of the sufferers [120,121]. Dementia developing after diagnosis of PD is termed as Parkinson’s disease dementia (PDD). The prevalence of PDD in PD after 8-10 years has been found to be nearly 75 % [122,123]. Risk factors for developing early dementia are old age and severity of motor symptoms [123]. Clinical diagnostic features associated with PDD are impairment in attention, executive functions and memory. Other behavioural features are apathy, hallucinations and delusions [124]. Sleep disorders like RBD may be present and has been found to be associated with increased risk of developing PDD [125]. There are no investigations to diagnose PDD but there is association with hippocampal and medial temporal lobe atrophy [126]. SPECT studies have found abnormalities in dopamine transporter and occipital region hypoperfusion [127]. Cholinergic deficits are also observed and treatment with cholinesterase inhibitors has been found to be useful in PDD [128]. Treatment is otherwise symptomatic. Prognosis varies but PDD sufferers have been found to have increased risk of mortality [129].
5.5. Dementia in HIV disease
The HIV-1 virus is known to cause AIDS and also other neurological disorders. These neurological disorders are known as HIV-associated neurocognitive disorders (HAND). The most severe form of HAND is HIV-associated dementia (HAD) [130]. The annual incidence of HAD in 1990’s was 7 % [131]. However, with the advent of highly active antiretroviral therapy (HAART), the incidence has decreased by more than half to about 2 to 4% [132-134]. The clinical features as part of the diagnostic criteriae include dementia, no evidence for presence of delirium nor any other cause for dementia [130]. Neuroinflammation in brain is observed. Viral proteins that are released from infected glial cells activate uninfected microglial cells and astrocytes to secrete cytokines and neurotoxins. This causes neuronal cell death i.e. neurodegeneration [135,136]. To help in detecting HAD, a rating scale has been developed which tests timed fingertapping, alternating hand sequence test and recall of four items at 2 minutes [137]. HAART is used as treatment of HAD. The aim is to suppress the virus and its replication in plasma and CNS [138]. Some of the drugs used in HAART regimen are a combination of efavirenz, lamivudine and zidovudine. Other medications like memantine, valproic acid and selegiline listed under adjunctive therapies have not been found to be useful in HAD [139]. HAD is associated with increased mortality with median survival time after dementia found to be 6 months [131].
The NAD or other dementias form a vital part of the fight against dementia and its consequences. Even though AD forms the bulk of dementia cases, knowledge and understanding of NAD might play an important role in the much needed quest for cure or prevention of dementia. More cutting-edge research into these diseases and their pathogenesis will help combat the spread and probably even onset of dementia.
References
1.Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology 2007;29(1-2):125-132.
2.Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, et al. Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol 2008 Sep;7(9):812-826.
3.Brookmeyer R, Evans DA, Hebert L, Langa KM, Heeringa SG, Plassman BL, et al. National estimates of the prevalence of Alzheimer's disease in the United States. Alzheimers Dement 2011 Jan;7(1):61-73.
4.Bowler JV, Hachinski V. Vascular cognitive impairment: a new approach to vascular dementia. Baillieres Clin Neurol 1995 Aug;4(2):357-376.
9.Chui HC, Mack W, Jackson JE, Mungas D, Reed BR, Tinklenberg J, et al. Clinical criteria for the diagnosis of vascular dementia: a multicenter study of comparability and interrater reliability. Arch Neurol 2000 Feb;57(2):191-196.
10.van der Flier WM, Scheltens P. Epidemiology and risk factors of dementia. J Neurol Neurosurg Psychiatry 2005 Dec;76 Suppl 5:v2-7.
11.Ikeda M, Hokoishi K, Maki N, Nebu A, Tachibana N, Komori K, et al. Increased prevalence of vascular dementia in Japan: a community-based epidemiological study. Neurology 2001 Sep 11;57(5):839-844.
12.Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, et al. Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54(11 Suppl 5):S4-9.
13.Harvey RJ, Skelton-Robinson M, Rossor MN. The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 2003 Sep;74(9):1206-1209.
14.Mathias JL, Burke J. Cognitive functioning in Alzheimer's and vascular dementia: a meta-analysis. Neuropsychology 2009 Jul;23(4):411-423.
15.Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999 Oct-Dec;13 Suppl 3:S115-23.
16.Sharp SI, Aarsland D, Day S, Sonnesyn H, Alzheimer's Society Vascular Dementia Systematic Review Group, Ballard C. Hypertension is a potential risk factor for vascular dementia: systematic review. Int J Geriatr Psychiatry 2011 Jul;26(7):661-669.
17.Di Carlo A, Baldereschi M, Amaducci L, Lepore V, Bracco L, Maggi S, et al. Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study. J Am Geriatr Soc 2002 Jan;50(1):41-48.
18.Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, et al. Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology 1995 Jun;45(6):1161-1168.
19.Gorelick PB. Risk factors for vascular dementia and Alzheimer disease. Stroke 2004 Nov;35(11 Suppl 1):2620-2622.
20.Hebert R, Lindsay J, Verreault R, Rockwood K, Hill G, Dubois MF. Vascular dementia : incidence and risk factors in the Canadian study of health and aging. Stroke 2000 Jul;31(7):1487-1493.
21.Perez L, Heim L, Sherzai A, Jaceldo-Siegl K, Sherzai A. Nutrition and vascular dementia. J Nutr Health Aging 2012 Apr;16(4):319-324.
22.Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, et al. Cerebral blood flow in dementia. Arch Neurol 1975 Sep;32(9):632-637.
23.Chui HC, Victoroff JI, Margolin D, Jagust W, Shankle R, Katzman R. Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers. Neurology 1992 Mar;42(3 Pt 1):473-480.
24.Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007 Nov;10(11):1387-1394.
25.Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993 Feb;43(2):250-260.
26.Mathias JL, Burke J. Cognitive functioning in Alzheimer's and vascular dementia: a meta-analysis. Neuropsychology 2009 Jul;23(4):411-423.
27.Ballard CG, Burton EJ, Barber R, Stephens S, Kenny RA, Kalaria RN, et al. NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia. Neurology 2004 Sep 28;63(6):983-988.
28.Ivan CS, Seshadri S, Beiser A, Au R, Kase CS, Kelly-Hayes M, et al. Dementia after stroke: the Framingham Study. Stroke 2004 Jun;35(6):1264-1268.
29.Tatemichi TK, Desmond DW, Paik M, Figueroa M, Gropen TI, Stern Y, et al. Clinical determinants of dementia related to stroke. Ann Neurol 1993 Jun;33(6):568-575.
30.Pohjasvaara T, Erkinjuntti T, Ylikoski R, Hietanen M, Vataja R, Kaste M. Clinical determinants of poststroke dementia. Stroke 1998 Jan;29(1):75-81.
31.Henon H, Durieu I, Guerouaou D, Lebert F, Pasquier F, Leys D. Poststroke dementia: incidence and relationship to prestroke cognitive decline. Neurology 2001 Oct 9;57(7):1216-1222.
34.Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 2001 Dec 15;358(9298):2049-2051.
35.Hara K, Shiga A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med 2009 Apr 23;360(17):1729-1739.
36.Fukutake T. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. J Stroke Cerebrovasc Dis 2011 Mar-Apr;20(2):85-93.
37.Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T. Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 2004 Nov 15;226(1-2):75-80.
38.Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012 Apr 3;78(14):1043-1050.
39.Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010 Jul;9(7):689-701.
40.PROGRESS Collaborative Group. Effects of a perindopril-based blood pressure lowering regimen on cardiac outcomes among patients with cerebrovascular disease. Eur Heart J 2003 Mar;24(5):475-484.
41.Roman GC, Salloway S, Black SE, Royall DR, Decarli C, Weiner MW, et al. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size. Stroke 2010 Jun;41(6):1213-1221.
42.Craig D, Birks J. Galantamine for vascular cognitive impairment. Cochrane Database Syst Rev 2006 Jan 25;(1)(1):CD004746.
43.Craig D, Birks J. Rivastigmine for vascular cognitive impairment. Cochrane Database Syst Rev 2005 Apr 18;(2)(2):CD004744.
44.Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol 2007 Sep;6(9):782-792.
45.Okazaki H, Lipkin LE, Aronson SM. Diffuse intracytoplasmic ganglionic inclusions (Lewy type) associated with progressive dementia and quadriparesis in flexion. J Neuropathol Exp Neurol 1961 Apr;20:237-244.
46.Lennox G, Lowe J, Landon M, Byrne EJ, Mayer RJ, Godwin-Austen RB. Diffuse Lewy body disease: correlative neuropathology using anti-ubiquitin immunocytochemistry. J Neurol Neurosurg Psychiatry 1989 Nov;52(11):1236-1247.
47.Kosaka K, Yoshimura M, Ikeda K, Budka H. Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree--a new disease? Clin Neuropathol 1984 Sep-Oct;3(5):185-192.
48.Gibb WR, Esiri MM, Lees AJ. Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia). Brain 1987 Oct;110 ( Pt 5)(Pt 5):1131-1153.
49.Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, et al. The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology 1990 Jan;40(1):1-8.
50.Perry RH, Irving D, Blessed G, Fairbairn A, Perry EK. Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 1990 Feb;95(2):119-139.
51.Stoll G, Jander S. Microglia. eLS: John Wiley & Sons, Ltd; 2001.
52.Yamada T, Hattori H, Miura A, Tanabe M, Yamori Y. Prevalence of Alzheimer's disease, vascular dementia and dementia with Lewy bodies in a Japanese population. Psychiatry Clin Neurosci 2001 Feb;55(1):21-25.
53.Stevens T, Livingston G, Kitchen G, Manela M, Walker Z, Katona C. Islington study of dementia subtypes in the community. Br J Psychiatry 2002 Mar;180:270-276.
54.Rahkonen T, Eloniemi-Sulkava U, Rissanen S, Vatanen A, Viramo P, Sulkava R. Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older. J Neurol Neurosurg Psychiatry 2003 Jun;74(6):720-724.
55.Zaccai J, McCracken C, Brayne C. A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing 2005 Nov;34(6):561-566.
56.Perez F, Helmer C, Dartigues JF, Auriacombe S, Tison F. A 15-year population-based cohort study of the incidence of Parkinson's disease and dementia with Lewy bodies in an elderly French cohort. J Neurol Neurosurg Psychiatry 2010 Jul;81(7):742-746.
57.McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005 Dec 27;65(12):1863-1872.
58.Ferman TJ, Boeve BF, Smith GE, Silber MH, Lucas JA, Graff-Radford NR, et al. Dementia with Lewy bodies may present as dementia and REM sleep behavior disorder without parkinsonism or hallucinations. J Int Neuropsychol Soc 2002 Nov;8(7):907-914.
59.Boeve BF, Silber MH, Ferman TJ. REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol 2004 Sep;17(3):146-157.
60.Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, et al. Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology 2011 Aug 30;77(9):875-882.
61.Harding AJ, Halliday GM. Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol 2001 Oct;102(4):355-363.
62.Burton EJ, Mukaetova-Ladinska EB, Perry RH, Jaros E, Barber R, O'Brien JT. Neuropathological correlates of volumetric MRI in autopsy-confirmed Lewy body dementia. Neurobiol Aging 2012 Jul;33(7):1228-1236.
63.Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997 Aug 28;388(6645):839-840.
64.Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 2004 Feb;55(2):164-173.
65.Gomez-Tortosa E, Newell K, Irizarry MC, Sanders JL, Hyman BT. alpha-Synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining. Acta Neuropathol 2000 Apr;99(4):352-357.
66.Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain 2002 Feb;125(Pt 2):391-403.
67.Watson R, Blamire AM, O'Brien JT. Magnetic resonance imaging in lewy body dementias. Dement Geriatr Cogn Disord 2009;28(6):493-506.
68.Lobotesis K, Fenwick JD, Phipps A, Ryman A, Swann A, Ballard C, et al. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology 2001 Mar 13;56(5):643-649.
69.McKeith I, O'Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007 Apr;6(4):305-313.
70.O'Brien JT, McKeith IG, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies. Br J Psychiatry 2009 Jan;194(1):34-39.
71.Gomperts SN, Rentz DM, Moran E, Becker JA, Locascio JJ, Klunk WE, et al. Imaging amyloid deposition in Lewy body diseases. Neurology 2008 Sep 16;71(12):903-910.
72.Lucetti C, Logi C, Del Dotto P, Berti C, Ceravolo R, Baldacci F, et al. Levodopa response in dementia with lewy bodies: a 1-year follow-up study. Parkinsonism Relat Disord 2010 Sep;16(8):522-526.
73.Ballard C, Kahn Z, Corbett A. Treatment of dementia with Lewy bodies and Parkinson's disease dementia. Drugs Aging 2011 Oct 1;28(10):769-777.
74.Aarsland D, Ballard C, Walker Z, Bostrom F, Alves G, Kossakowski K, et al. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol 2009 Jul;8(7):613-618.
75.Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev 2012 Mar 14;3:CD006504.
76.Ballard C, O'Brien J, Morris CM, Barber R, Swann A, Neill D, et al. The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease. Int J Geriatr Psychiatry 2001 May;16(5):499-503.
77.Walker Z, Allen RL, Shergill S, Mullan E, Katona CL. Three years survival in patients with a clinical diagnosis of dementia with Lewy bodies. Int J Geriatr Psychiatry 2000 Mar;15(3):267-273.
78.McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, et al. Dementia with Lewy bodies. Lancet Neurol 2004 Jan;3(1):19-28.
79.Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor neuron dysfunction in frontotemporal dementia. Brain 2011 Sep;134(Pt 9):2582-2594.
80.Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology 2002 Jun 11;58(11):1615-1621.
81.Rosso SM, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y, et al. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain 2003 Sep;126(Pt 9):2016-2022.
82.Borroni B, Alberici A, Grassi M, Rozzini L, Turla M, Zanetti O, et al. Prevalence and demographic features of early-onset neurodegenerative dementia in Brescia County, Italy. Alzheimer Dis Assoc Disord 2011 Oct;25(4):341-344.
83.Mercy L, Hodges JR, Dawson K, Barker RA, Brayne C. Incidence of early-onset dementias in Cambridgeshire, United Kingdom. Neurology 2008 Nov 4;71(19):1496-1499.
84.Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998 Dec;51(6):1546-1554.
85.Johnson JK, Diehl J, Mendez MF, Neuhaus J, Shapira JS, Forman M, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol 2005 Jun;62(6):925-930.
86.Neary D, Snowden J, Mann D. Frontotemporal dementia. Lancet Neurol 2005 Nov;4(11):771-780.
87.Rascovsky K, Hodges JR, Kipps CM, Johnson JK, Seeley WW, Mendez MF, et al. Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions. Alzheimer Dis Assoc Disord 2007 Oct-Dec;21(4):S14-8.
89.Tambuyzer BR, Ponsaerts P, Nouwen EJ. Microglia: gatekeepers of central nervous system immunology. J Leukoc Biol 2009 Mar;85(3):352-370.
90.Nestor PJ, Graham NL, Fryer TD, Williams GB, Patterson K, Hodges JR. Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula. Brain 2003 Nov;126(Pt 11):2406-2418.
91.Lillo P, Hodges JR. Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J Clin Neurosci 2009 Sep;16(9):1131-1135.
92.Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011 Oct 20;72(2):257-268.
93.DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011 Oct 20;72(2):245-256.
94.Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 2007 Jul;114(1):5-22.
95.Mackenzie IR, Neumann M, Bigio EH, Cairns NJ, Alafuzoff I, Kril J, et al. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 2010 Jan;119(1):1-4.
96.Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol 2011 Feb;10(2):162-172.
97.Rohrer JD, Lashley T, Schott JM, Warren JE, Mead S, Isaacs AM, et al. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain 2011 Sep;134(Pt 9):2565-2581.
98.Mackenzie IR, Rademakers R, Neumann M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 2010 Oct;9(10):995-1007.
99.Agosta F, Canu E, Sarro L, Comi G, Filippi M. Neuroimaging findings in frontotemporal lobar degeneration spectrum of disorders. Cortex 2012 Apr;48(4):389-413.
100.Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR. Clinical staging and disease progression in frontotemporal dementia. Neurology 2010 May 18;74(20):1591-1597.
101.McKhann GM, Albert MS, Grossman S, Miller B, Dickson D, Trojanowski JQ. Clinical and Pathological Diagnosis of Frontotemporal Dementia. Report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 2001;58:1803-1809.
102.Yokota O, Tsuchiya K, Arai T, Yagishita S, Matsubara O, Mochizuki A, et al. Clinicopathological characterization of Pick's disease versus frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions. Acta Neuropathol 2009 Apr;117(4):429-444.
103.Binetti G, Locascio JJ, Corkin S, Vonsattel JP, Growdon JH. Differences between Pick disease and Alzheimer disease in clinical appearance and rate of cognitive decline. Arch Neurol 2000 Feb;57(2):225-232.
104.Cohen BJ. Theory and Practice of Psychiatry. New York: Oxford University Press; 2003.
105.Munoz DJ, Morris HR, Rossor M. Pick’s Disease. In: Dickson DW, Weller RO (eds.) Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders, Second Edition. Blackwell Publishing Ltd.; 2011. p156-164.
106.Aguzzi A, Heikenwalder M. Pathogenesis of prion diseases: current status and future outlook. Nat Rev Microbiol 2006 Oct;4(10):765-775.
107.Sikorska B, Knight R, Ironside JW, Liberski PP. Creutzfeldt-Jakob Disease. In: Ahmad SI (ed.) Neurodegenerative Diseases. Landes Bioscience and Springer Science+Business Media; 2012. p76-90.
108.Rosenbloom MH, Atri A. The evaluation of rapidly progressive dementia. Neurologist 2011 Mar;17(2):67-74.
109.Aguzzi A, Calella AM. Prions: protein aggregation and infectious diseases. Physiol Rev 2009 Oct;89(4):1105-1152.
110.Geschwind MD, Shu H, Haman A, Sejvar JJ, Miller BL. Rapidly progressive dementia. Ann Neurol 2008 Jul;64(1):97-108.
111.Brown P, Gibbs CJ,Jr, Rodgers-Johnson P, Asher DM, Sulima MP, Bacote A, et al. Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 1994 May;35(5):513-529.
112.Johnson RT, Gibbs CJ,Jr. Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. N Engl J Med 1998 Dec 31;339(27):1994-2004.
114.Heath CA, Cooper SA, Murray K, Lowman A, Henry C, MacLeod MA, et al. Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease. Ann Neurol 2010 Jun;67(6):761-770.
115.A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993 Mar 26;72(6):971-983.
116.Gil JM, Rego AC. Mechanisms of neurodegeneration in Huntington's disease. Eur J Neurosci 2008 Jun;27(11):2803-2820.
117.Lovestone S. Alzheimer’s Disease and Other Dementias (Including Pseudodementias). In: David AS, Fleminger S, Kopelman MD, Lovestone S, Mellers JDC (eds.) Lishman’s Organic Psychiatry, Fourth Edition. Blackwell Publishing; 2009. p543-616.
118.Sturrock A, Leavitt BR. The clinical and genetic features of Huntington disease. J Geriatr Psychiatry Neurol 2010 Dec;23(4):243-259.
119.Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004 Jul;10 Suppl:S10-7.
120.Emre M. Dementia associated with Parkinson's disease. Lancet Neurol 2003 Apr;2(4):229-237.
121.Perez F, Helmer C, Foubert-Samier A, Auriacombe S, Dartigues JF, Tison F. Risk of dementia in an elderly population of Parkinson's disease patients: A 15-year population-based study. Alzheimers Dement 2012 May 30.
122.Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003 Mar;60(3):387-392.
123.Aarsland D, Kurz MW. The epidemiology of dementia associated with Parkinson's disease. Brain Pathol 2010 May;20(3):633-639.
124.Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord 2007 Sep 15;22(12):1689-707; quiz 1837.
125.Postuma RB, Bertrand JA, Montplaisir J, Desjardins C, Vendette M, Rios Romenets S, et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: A prospective study. Mov Disord 2012 May;27(6):720-726.
126.Weintraub D, Doshi J, Koka D, Davatzikos C, Siderowf AD, Duda JE, et al. Neurodegeneration across stages of cognitive decline in Parkinson disease. Arch Neurol 2011 Dec;68(12):1562-1568.
127.Rossi C, Volterrani D, Nicoletti V, Manca G, Frosini D, Kiferle L, Unti E, De Feo P, Bonuccelli U, Ceravolo R. “Parkinson-dementia” diseases: A comparison by double tracer SPECT studies. Parkinsonism and Related Disorders 2009 (15)762-766.
128.Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database Syst Rev 2012 Mar 14;3:CD006504.
129.Levy G, Tang MX, Louis ED, Cote LJ, Alfaro B, Mejia H, et al. The association of incident dementia with mortality in PD. Neurology 2002 Dec 10;59(11):1708-1713.
130.Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007 Oct 30;69(18):1789-1799.
131.McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, et al. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 1993 Nov;43(11):2245-2252.
132.Sacktor N. The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol 2002 Dec;8 Suppl 2:115-121.
133.Mocroft A, Katlama C, Johnson AM, Pradier C, Antunes F, Mulcahy F, et al. AIDS across Europe, 1994-98: the EuroSIDA study. Lancet 2000 Jul 22;356(9226):291-296.
134.Heaton RK, Clifford DB, Franklin DR,Jr, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010 Dec 7;75(23):2087-2096.
135.Nath A. Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis 2002 Dec 1;186 Suppl 2:S193-8.
136.del Palacio M, Alvarez S, Munoz-Fernandez MA. HIV-1 infection and neurocognitive impairment in the current era. Rev Med Virol 2012 Jan;22(1):33-45.
137.Sacktor NC, Wong M, Nakasujja N, Skolasky RL, Selnes OA, Musisi S, et al. The International HIV Dementia Scale: a new rapid screening test for HIV dementia. AIDS 2005 Sep 2;19(13):1367-1374.
138.McArthur JC, Brew BJ, Nath A. Neurological complications of HIV infection. Lancet Neurol 2005 Sep;4(9):543-555.
139.Uthman OA, Abdulmalik JO. Adjunctive therapies for AIDS dementia complex. Cochrane Database Syst Rev 2008 Jul 16;(3)(3):CD006496.
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Abhishek Shastri, Domenico Marco Bonifati and Uday Kishore
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