What is ‘early onset dementia’?

There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelarted onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a ‘presenile dementia’. Since the 1980s, ‘senile dementia of Alzheimer type’ (SDAT) and ‘Alzheimer's disease’ have been considered to belong to the same pathological entity and both are now known as ‘dementia of Alzheimer's type (DAT)’ or merely ‘Alzheimer's disease’. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.     

Plasma levels of soluble receptor for advanced glycation end products in Alzheimer's disease

Background: A decreased plasma level of soluble form of the receptor for advanced glycation end products (sRAGE) in patients with Alzheimer's disease (AD) has been reported. However, no evidence has shown whether the sRAGE plasma level of AD patients may differentiate from other types of dementia. Methods: Our study assessed sRAGE concentrations in the following 121 individuals in Chongqing area: 36 patients with AD, 12 with vascular dementia (VaD), 14 with mixed dementia (MD), 24 with other dementia (OD) including Parkinson's disease dementia, frontotemporal dementia, paralytic dementia and 35 cognitively normal controls. The total plasma level of sRAGE was determined using sandwich ELISA method. Results: sRAGE concentration in AD is significantly decreased compared with healthy controls. However, the receiver operating characteristic curve analysis of sRAGE between the AD and the control shows a low diagnostic accuracy. Conclusions: Our results demonstrate that sRAGE may assist the diagnosis of AD from normal individuals, but cannot differentiate AD from VaD, MD or OD.     

Picture naming deficits in vascular dementia and Alzheimer's disease

Abstract

Picture naming deficits in Alzheimer's disease (AD) have been extensively studied but less is known about anomia in vascular dementia (VaD). We tested sources of anomia in these two dementia types by administering an extensive naming battery to 10 patients with VaD, 13 patients with probable AD, and 20 healthy age-and education-matched controls. Both dementia groups evidenced a semantic component in their anomia but the semantic deficit was more clearcut in the patients with AD than in the patients with VaD even though the groups were matched on dementia severity. Case-by-case analyses showed considerable performance variability but confirmed that when anomia is present, it commonly has a semantic component in both VaD and AD.     

Apolipoprotein e genotype and late paraphrenia

Patients with late paraphrenia or late onset schizophrenia frequently have associated cognitive impairment which may in some cases progress to a recognized dementia. The frequency of the apoE ?4 allele is high in individuals who develop Alzheimer's disease. Twenty-three patients with late paraphrenia were genotyped for ApoE. The frequency of the ?4 allele was comparable with that found in a large group of centenarians, but lower than previously reported from populations of normal controls and Alzheimer's disease patients. Two out of three male patients tested had the rare ?2/?2 genotype, which was not found in any of the females.     

Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease

Controversy exists regarding the apolipoprotein E (ApoE) epsilon4 allele association with vascular dementia (VaD), ranging from increased epsilon4 frequency, similar to that found for Alzheimer's disease (AD), to no association between the epsilon4 allele and VaD. To clarify further the relationship between ApoE alleles polymorphism and cerebrovascular disease (CVD) in demented and cognitively impaired patients, we examined the ApoE phenotypes in a sample of 280 patients: 155 with AD, 21 with VaD, 32 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) but without CVD, and 27 in which vascular disease was the most probable cause of cognitive decline [vascular mild cognitive impairment (VMCI)]. Our results show that the frequency of the ApoE epsilon4 allele in patients over 70 years old with clinically diagnosed VaD and VMCI does not differ significantly from that of controls. In contrast, ApoE epsilon4 allele-bearing individuals had greater risk of having late-onset AD (OR = 8.8; 95% CI 3.7-21.0), or non-vascular cognitive impairment (OR = 7.0; 95% CI 2.5-19.0).     

Frequency of early and late-onset dementias in a Japanese memory disorders clinic

The aim of this study was to compare the diagnostic profiles of patients with early (age<65 years) and late (age>or=65 years) onset of dementia in a memory disorders clinic in Japan. A total of 512 consecutive memory clinic patients were evaluated using clinical information and results of examinations. Diagnosis of dementia was made according to DSM-III-R, and that of subtypes according to standard diagnostic criteria. A total of 464 patients met the criteria for dementia. Amongst late-onset patients (n=430), Alzheimer's disease (AD) (48.1%) was the most frequent cause of dementia, followed by AD with cerebrovascular disease (CVD) (31.4%), vascular dementia (VaD) (9.1%), dementia with Lewy bodies (DLB) (3.7%), frontotemporal lobar degeneration (FTLD) (1.6%), and others (5.8%). On the contrary, amongst early onset patients (n=34), the most common dementia diagnosis was AD (38.2%), followed by VaD (23.5%), FTLD (14.7%), AD with CVD (5.9%), DLB (2.9%), and others (17.6%). FTLD and VaD were significantly more common in the early onset group. All patients, but one, with DLB and Parkinson's disease dementia were late-onset. The relative frequencies of AD, VaD, and DLB in our series are consistent with epidemiologic findings in several Western countries; however, the frequency of FTLD is not consistent with the previous findings presenting high frequency in late-onset patients in some Western countries.     

EEG spectral analysis in vascular and Alzheimer dementia

The role of EEG spectral analysis in the diagnosis of syndromes of dementia is still disputed. Since there have been few studies dealing with the profile of power spectra, the present investigation has focused on this aspect, constructing power spectra taken from 16 derivations and calculated by averaging twenty 2 sec epochs, using a serial array of frequencies from 1 to 32 Hz. The spectral analysis of the EEG, recorded under awake resting eyes closed (REC) and open (REO) conditions, was performed in 50 patients with Alzheimer's disease (AD), 37 with vascular dementia (VaD) and 36 elderly controls. Three spectral profiles were found under REC: (i) type A, showing a dominant 6.5–12 Hz peak (44% AD, 97.3% VaD), although lower than in controls; (ii) type B, lacking a dominant peak in the 6.5–12 Hz band, but characterised by high power in 1–6.5 Hz band (44% AD, 2.7% VaD); (iii) type C, corresponding to a flat, low voltage, spectrum (12% AD). Unlike controls, demented patients showed an increased REO/REC power ratio in the 6.5–12 Hz band, especially in those with type B spectra. AD patients with type B spectra had an earlier age of disease onset.     

Endothelin‐converting enzyme‐1 in Alzheimer's disease and vascular dementia

J. C. Palmer, P. G. Kehoe and S. Love (2010) Neuropathology and Applied Neurobiology 36, 487–497
Endothelin‐converting enzyme‐1 in Alzheimer's disease and vascular dementia Aims: Alzheimer's disease (AD) is believed to be caused by the accumulation of amyloid beta (Aβ) peptide within the brain. Endothelin‐converting enzyme‐1 and 2 (ECE‐1 and ECE‐2) are expressed in endothelial cells and neurones, respectively, and both cleave ‘big endothelin’ to produce the vasoconstrictor endothelin‐1 (ET‐1). ECE‐1 and ECE‐2 also degrade Aβ. AD patients have regionally reduced microvascular blood flow in the brain, with impaired endothelium‐dependent relaxation and cerebrovascular autoregulation, and abnormal production of ET‐1 has been demonstrated in mice overexpressing amyloid precursor protein. We recently found ECE‐2 mRNA and protein to be elevated in the brain in AD. In vitro, expression of ECE‐2 was upregulated by Aβ. Our aims for this study were to examine expression of ECE‐1 (which has 57% homology with ECE‐2) in temporal cortex from patients with AD, vascular dementia (VaD) and controls. Methods: We examined the distribution of ECE‐1 with immunohistochemistry, and measured ECE‐1 mRNA by real‐time polymerase chain reaction (PCR). ECE‐1 protein levels were measured by western blot, and results analysed before and after adjustment for factor VIII‐related antigen. Results: We showed ECE‐1 to be in vascular endothelial cells. We did not find significant differences in ECE‐1 mRNA or protein levels (either full‐length ECE‐1 or the soluble spliced variant, ECE‐1sv) in AD or VaD compared with controls. Conclusions: Our findings suggest that any disease‐specific contribution of ECE‐1 to the accumulation of Aβ or reduction in local microvascular blood flow in AD or VaD is probably small, with abnormal production of ET‐1 being more likely to reflect Aβ‐mediated upregulation of ECE‐2.     

Apolipoprotein E in Taiwan Chinese patients with dementia

To clarify whether Alzheimer's disease (AD) and vascular dementia (VaD) share the same risk factors in Taiwan Chinese patients. Using the criteria of the NINCDS- ADRDA and NINDS-AIREN, 154 AD patients, 30 VaD patients, and 112 controls were enrolled. Their apolipoprotein E (ApoE) genes, extracted from peripheral blood leukocytes, were analyzed. The epsilon4 allele frequency was significantly higher in AD patients than in the control group. The odds ratio of carrying at least one copy of the epsilon4 allele in AD patients is 2.7 compared with control subjects. There was no significant difference between the VaD patients and the control subjects in their ApoE epsilon4 or epsilon2 allele frequency. The present study demonstrates a strong association between the ApoE epsilon4 allele and AD, but not between the ApoE epsilon4 allele and VaD. This suggests that AD and VaD do not share the same pathogenesis and deserve further investigation.     

Dementia Rating Scale Performance: A Comparison of Vascular and Alzheimer's Dementia

Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.     

Apolipoprotein E gene polymorphism in Indian patients with Alzheimer's disease and vascular dementia

The association of apolipoprotein E (ApoE) gene polymorphism with Alzheimer's disease (AD) has been reported in several populations including one from a rural community in North India. However, the association of ApoE polymorphism with vascular dementia (VaD) is yet to be established in this population. In a case-control study involving 54 cases of dementia (29 AD and 25 VaD) and 76 age-matched healthy controls, the frequency of epsilon4 allele was significantly higher among cases of AD and VaD compared with controls (p < 0.001). The epsilon3epsilon3 (p < 0.05) and epsilon2epsilon3 (p < 0.001) genotypes were found to be protective. The odds of developing AD or VaD were 4.4 and 3.7 times higher, respectively, in the presence of even a single epsilon4 allele. Our results suggest that the increased risk of developing AD or VaD is similar among Asian Indians with ApoE epsilon4 compared with the Caucasian population.     

Treatment of vascular dementia—evidence from clinical trials with cholinesterase inhibitors

Abstract

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. Also, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as in patients with AD plus CVD, have demostrated improvement in cognition, behavior and activites of daily living.     

Vascular aspects of cognitive impairment and dementia

Hypertension and stroke are highly prevalent risk factors for cognitive impairment and dementia. Alzheimer''s disease (AD) and vascular dementia (VaD) are the most common forms of dementia, and both conditions are preceded by a stage of cognitive impairment. Stroke is a major risk factor for the development of vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose to AD. Hypertension is a major risk factor for stroke, thus linking hypertension to VCI and VaD, but hypertension is also an important risk factor for AD. Reducing these two major, but modifiable, risk factors—hypertension and stroke—could be a successful strategy for reducing the public health burden of cognitive impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) and the manipulation of factors involved in the renin–angiotensin system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to reduce the risk of developing hypertension and stroke, thereby reducing dementia risk. This paper will review the research conducted on the relationship between hypertension, stroke, and dementia and also on the impact of LC-n3-FA or antihypertensive treatments on risk factors for VCI, VaD, and AD.     

A cross-sectional study on thyroid status in North Indian elderly outpatients with dementia

Background:

Several population based studies have demonstrated an association between hypo-or hyperthyroidism and dementia in last two decades. As a consequence, thyroid stimulating hormone has become part of the screening laboratory test for dementia.

Aim:

The aim of the present study was to evaluate the association between thyroid function and Alzheimer''s disease (AD) and vascular dementia (VaD) and to determine the risk of AD and VaD in clinically euthyroid patients.

Materials and Methods:

A cross-sectional hospital based study was carried out in subjects diagnosed with AD/VaD and were assessed for thyroid status as routine screening test.

Results:

Free T3, free T4 and TSH were studied in 114 AD patients (mean age: 65 years), 35 VaD patients (mean age: 62 years) and 105 control subjects (mean age: 62 years). In AD group, TSH levels were significantly lower than controls (P = 0.00) and for each unit increase in TSH level, the odds of having dementia decreased by 37.1%. No such relation was seen in VaD.

Conclusion:

The results suggest a consistent association of subclinical hyperthyroidism and AD.     

Association of depression with Alzheimer's disease and vascular dementia in an elderly Arab population of Wadi-Ara, Israel

OBJECTIVES: Because dementia and depression share common risk factors, we investigated risk factors for depression in Arab subjects with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: In a cross-sectional population-based study, we conducted a door-to-door survey of all adults over age 60 in an Arab community of rural Israel. We conducted interviews, gave questionnaires, and collected DNA blood specimens for determination of ApoE genotype. RESULTS: Of the 823 individuals in this naturalistic sample, 168 had dementia of Alzheimer's type (DAT) and 49 had VaD. Vascular risk factors, including the ApoE-epsilon4 allele, were more prevalent among VaD than DAT subjects. Depressive symptoms were present in 57% of DAT patients and 86% of VaD patients. Depressed DAT individuals had a greater history of ischemic cardiovascular or cerebrovascular (CV/CBV) disease than non-depressed DAT subjects, but depressed DAT subjects were less likely to have the ApoE-epsilon4 allele. Within the VaD group, there was no difference in the distribution of cardiovascular risk factors in individuals with and without depressive symptoms, and ApoE-epsilon4 was more prevalent among subjects with depressive symptoms. CONCLUSIONS: Depressive symptomatology is prevalent among subjects with dementias in this Arab community. History of CV/CBV is associated with the presence of depressive symptoms in DAT. Further studies are needed to clarify the role of ApoE in depression onset in different ethnic groups with DAT.     

Argyrophilic grain disease: A late‐onset dementia with distinctive features among tauopathies

Argyrophilic grain disease (AgD) is a late‐onset dementia morphologically characterized by the presence of abundant spindle‐shaped argyrophilic grains (ArG) in neuronal processes and coiled bodies in oligodendrocytes. AgD changes consist of the microtubule‐associated protein tau in an abnormally and hyperphosphorylated state and are mainly found in limbic regions, for example, in the hippocampus, the entorhinal and transentorhinal cortices and the amygdala. AgD shows a significant correlation with advancing age, and it became apparent from recent clinicopathological studies that it might account for approximately 5% of all dementia cases. Further immunohistochemical and biochemical studies revealed that AgD is a four‐repeat (4R) tauopathy similar to PSP and corticobasal degeneration (CBD), but distinct from Alzheimer's disease (AD) and Pick's disease. Moreover, a common genetic background regarding the tau gene haplotype has been suggested for AgD, PSP and CBD. However, although there are currently only limited data available, AgD seems to be clinically distinct from PSP and CBD and shares rather features of (mild) AD or other forms of ‘limbic’ dementias, among them senile dementia with tangles and the localized form of AD.     

Genetic characteristics of dementia in Taiwan

The most common causes of dementia in Taiwan are Alzheimer's disease (AD) followed by vascular dementia (VaD). Several genetic studies have documented an increased risk of AD among apolipoprotein E gene allele 4 (ApoE4) carriers in Taiwanese (ethnic Chinese). Although ApoE4 is considered the most important risk factor for AD, the ApoE4 allele frequency is lower in Taiwanese (around 7%), than that in most Caucasian populations (over 10%). This phenomenon raises the hypothesis that low ApoE4 allele frequency contributes to the low prevalence of AD in Taiwanese. Other studies of the genetic impacts on modulation or regulation of manifestations, progression, and treatment response of AD in Taiwan have been inconclusive. Familial AD, which is conferred by PS1 gene mutation has been identified. There were very few studies of fronto-temporal dementia (FTD) or dementia with Lewy body (DLB) in Taiwan. Genetic studies of VaD remain limited and only NOTCH3 gene mutation has been detected in a Taiwanese cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) family. Limited data indicated that non- ApoE4-associated AD may represent a larger proportion of AD in Taiwanese, suggesting the existence of novel genetic factors which remain to be identified.     

Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia

Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.     

Addition of MHPG to Alzheimer's disease biomarkers improves differentiation of dementia with Lewy bodies from Alzheimer's disease but not other dementias

BackgroundOverlapping clinical features make it difficult to distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and other dementia types. In this study we aimed to determine whether the combination of cerebrospinal fluid (CSF) biomarkers, amyloid-β₄₂ (Aβ₄₂), total tau protein (t-tau), and phosphorylated tau protein (p-tau), in combination with 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), could be useful in discriminating DLB from vascular dementia (VaD) and frontotemporal dementia (FTD), as we previously demonstrated for differentiation of DLB from AD.MethodsWe retrospectively analyzed concentrations of MHPG, Aβ₄₂, t-tau, and p-tau in CSF in patients with DLB, AD, VaD, and FTD. Using previously developed multivariate logistic regression models we assessed the diagnostic value of these CSF parameters.ResultsThe currently used combination of Aβ₄₂, t-tau, and p-tau yielded a sensitivity of 61.9% and a specificity of 91.7% for the discrimination between DLB and AD, but could not discriminate between DLB and VaD or FTD. The addition of MHPG to Aβ₄₂, t-tau, and p-tau improves the discrimination of DLB from AD, yielding a sensitivity of 65.1% and specificity of 100%, but could not distinguish DLB from other forms of dementia.ConclusionsOur results confirm in a separate patient cohort that addition of MHPG to Aβ₄₂, t-tau, and p-tau improves the discrimination of DLB from AD but not the differentiation of DLB from VaD or FTD.     

The prevalence of dementia in urban and rural areas of China

ObjectiveThe Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.MethodsFor the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures.ResultsThe prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71–5.57), 3.21% (95% CI, 2.87–3.55), and 1.50% (95% CI, 1.26–1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations.ConclusionsA notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban–rural differences.