Neuropsychological differentiation of Alzheimer's disease from vascular dementia

The purpose of this study was to determine whether cognitive test performances alone could distinguish patients with probable Alzheimer's disease from those with probable vascular dementia. Sixty-eight outpatients with clinical diagnoses of either Alzheimer's disease or vascular dementia were administered a brief battery of neuropsychological tests. Scores from the Boston Naming Test and the Hopkins Verbal Learning Test were identified as most discriminating of the groups. Seventy-seven per cent of the sample was correctly classified by a stepwise discriminant function analysis. Results of this study indicate that selected neuropsychological tests have moderate concurrent utility in the differential diagnosis of dementia.     

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.     

The accuracy of early diagnosis and predictors of death in Alzheimer's disease and vascular dementia--a follow-up study

A total of 87 patients with mild or moderate degree of dementia of the Alzheimer type (AD) or vascular dementia (VD) was identified (DSM-III criteria), and their cognitive capacity was evaluated by means of rating scales and psychometric tests. Three years later 30 patients (34%) were dead. Significantly more VD than AD patients died. Eight of the survivors declined to participate in a follow-up study, and 1 patient was excluded by mistake. Of the survivors, 17 had indisputably suffered cognitive decline during the follow-up period (4 VD and 13 AD, 35%). In the case of 11 patients (2 VD and 9 AD) cognitive decline remained doubtful, and 20 patients (9 VD and 11 AD, 42%) underwent no intellectual deterioration during the follow-up period. The results underline the problems of early diagnosis of dementia according to DSM-III criteria. For both sexes a high ischemia score and a low body mass index predicted death. A low score on a verbal fluency test predicted death for men but not for women, and a high difference between systolic and diastolic blood pressure increased the risk of death for men but not for women.     

Critical Flicker Fusion Threshold in patients with Alzheimer's disease and vascular dementia

BACKGROUND: Critical Flicker Fusion Threshold (CFFT) is a psychophysical threshold and in psychological terms is regarded as a measure of information processing capacity. The test has previously been shown to be a valid and reliable measure of CNS functioning in patients with Alzheimer's disease and may be a useful as a screening measure for the early detection of Alzheimer's disease (AD). METHODS: Consecutive referrals to the Wakefield Memory Clinic who met DSM-IV criteria for AD or vascular dementia (VaD) were invited to take part in the study. A range of neuropsychological tests and CFFT were administered to the two groups using standardised protocols and the ability of these various tests to distinguish between the two conditions was investigated. RESULTS: Forty-six patients were included in the study. Of the various tests, only the descending component of CFFT and word fluency were significantly different in the two groups. In addition, the descending threshold had a sensitivity of 83% and a specificity of 69%. CONCLUSION: CFFT could be useful as a screening instrument for early AD when combined with other measures and could facilitate the decision to commence antidementia treatment at an early stage. Further longitudinal work is needed to establish this.     

The role of vascular dementia associated genes in patients with Alzheimer's disease: A large case–control study in the Chinese population

AimThe role of vascular dementia (VaD)‐associated genes in Alzheimer''s disease (AD) remains elusive despite similar clinical and pathological features. We aimed to explore the relationship between these genes and AD in the Chinese population.MethodsEight VaD‐associated genes were screened by a targeted sequencing panel in a sample of 3604 individuals comprising 1192 AD patients and 2412 cognitively normal controls. Variants were categorized into common variants and rare variants according to minor allele frequency (MAF). Common variant (MAF ≥ 0.01)‐based association analysis was conducted by PLINK 1.9. Rare variant (MAF < 0.01) association study and gene‐based aggregation testing of rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test‐Optimal (SKAT‐O test), respectively. Age at onset (AAO) and Mini‐Mental State Examination (MMSE) association studies were performed with PLINK 1.9. Analyses were adjusted for age, gender, and APOE ε4 status.ResultsFour common COL4A1 variants, including rs874203, rs874204, rs16975492, and rs1373744, exhibited suggestive associations with AD. Five rare variants, NOTCH3 rs201436750, COL4A1 rs747972545, COL4A1 rs201481886, CST3 rs765692764, and CST3 rs140837441, showed nominal association with AD risk. Gene‐based aggregation testing revealed that HTRA1 was nominally associated with AD. In the AAO and MMSE association studies, variants in GSN, ITM2B, and COL4A1 reached suggestive significance.ConclusionCommon variants in COL4A1 and rare variants in HTRA1, NOTCH3, COL4A1, and CST3 may be implicated in AD pathogenesis. Besides, GSN, ITM2B, and COL4A1 are probably involved in the development of AD endophenotypes.     

Clinical utility of computed tomography in the assessment of dementia: a memory clinic study

OBJECTIVE: To define the influence of computed tomography (CT) on clinical decision-making in the outpatient evaluation of dementia. DESIGN: A case series in which two physicians reviewed standardised data extracted from clinical records, first blind to CT results, and then with CT results. Clinical decisions made with and without the input of CT were compared. The study was based in an outpatient referral centre for the assessment of memory disorders and dementia. The study involved 146 participants who were diagnosed with dementia after their first clinic visit, had Mini Mental State Examination scores >12, were aged >65 years, and had no history of neurologic disease. RESULTS: CT impacted on diagnosis in an average of 12% (+/-2), and on treatment plan in 11% (+/-2) of cases. Physicians predicted a priori which cases CT may influence with an average sensitivity of 28% (+/-2), and specificity of 78.5% (+/-1.5). There was no statistically significant relationship between diagnostically uncertain cases and helpful CT scans [average chi(2) = 1.121 (+/-1.116), p = ns]. Blind to CT physicians appropriately identified cerebrovascular disease with an average sensitivity of 63% (+/-3), and specificity of 93.5% (+/-3.5). CONCLUSIONS: In the outpatient setting, CT may be expected to impact on diagnosis and treatment of dementia in 10% to 15% of cases. Memory clinic physicians recognise and treat cerebrovascular risk factors with reasonable sensitivity and specificity without the input of CT.     

A review of the epidemiological transition in dementia--cross-national comparisons of the indices related to Alzheimer's disease and vascular dementia.

OBJECTIVE: To examine temporal changes in the prevalence of dementia and associated factors. METHOD: All publications on the epidemiology of dementia were identified using a medline search for the years 1966-1999. RESULTS: Alzheimer's disease (AD) has become nearly twice as prevalent as vascular dementia (VaD) in Korea, Japan, and China since transition in early 1990s. Prior to this, in the 1980s, VaD was more prevalent than AD in these countries. In Nigeria, the prevalence of dementia was low. Indian studies were contradictory, with both AD and VaD being more prevalent in different studies. American and European studies consistently reported AD to be more prevalent than VaD. CONCLUSION: A theoretical model of transition from low incidence-high mortality society to high incidence-high mortality society to low incidence-low mortality society may explain these findings. Rigorous testing in prospective, longitudinal and population-based cross-national studies using culture-fair diagnostic instruments is required.     

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia

Objectives. Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. Design. Cross-sectional comparative study. Setting. Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. Methods. Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). Results. Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p=0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p=0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p=0.046). There were no significant differences in LP or TAC between the three groups. Conclusions. Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation. Copyright © 1998 John Wiley & Sons, Ltd.     

Long-term safety and cognitive effects of galantamine in the treatment of probable vascular dementia or Alzheimer's disease with cerebrovascular disease.

The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with vascular dementia (VaD) and Alzheimer's disease (AD) with cerebrovascular disease (CVD) suggests a potential role for cholinomimetic therapy. Initial studies of galantamine demonstrated cognitive, behavioral, and functional benefits in these populations. 326 patients with VaD or AD with CVD who completed an initial 12-month trial were treated with galantamine 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). Galantamine (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older dementia patients, included depression, agitation, and insomnia. Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. Patients taking galantamine for the entire study demonstrated the least cognitive decline on AD Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of galantamine were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in VaD patients and for 12 months in patients with AD with CVD. Long-term (up to 24 months) galantamine therapy in patients with VaD and AD with CVD is well tolerated and associated with prolonged maintenance of cognitive function.     

The characterisation and impact of 'fluctuating' cognition in dementia with Lewy bodies and Alzheimer's disease

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in all the major dementias, particularly dementia with Lewy bodies (DLB) where it is one of three core clinical diagnostic features. The purpose of this study was to characterise FC and determine its impact upon activities of daily living. METHODS: Forty matched subjects (15 DLB, 15 AD, 10 elderly controls) were assessed using the activities of daily living scale (ADLD), the cognitive drug research (CDR) computerised neuropsychological test battery and a semi-standardised assessment of FC. The CDR battery was completed three times across a 1-week period, to evaluate variability in attention, visuospatial ability, working memory and delayed recall. RESULTS: There was a strong positive correlation between clinical FC scores and total mean ADLD. Measures of cognitive variability also demonstrated strong significant correlations with independent clinical severity ratings of FC across several cognitive domains. These associations were most powerful between attentional measures and clinical FC ratings. CONCLUSIONS: Although attention is the cognitive domain which fluctuates most markedly, other cognitive domains are also affected. FC also has a significant independent impact on activities of daily living.