Similar patterns of cognitive deficits in the preclinical phases of vascular dementia and Alzheimer's disease.

We investigated whether (1) cognitive deficits are present among persons who will be diagnosed with vascular dementia (VaD) 3 years later, and (2) the pattern of such deficits is similar to that observed in preclinical Alzheimer's disease (AD). The VaD diagnosis was a diagnosis of post-stroke dementia. Population-based samples of 15 incident VaD cases, 43 incident AD cases, and 149 normal controls were compared on tests of episodic and short-term memory, verbal fluency, and visuospatial skill. Both dementia groups showed preclinical impairment relative controls on tasks assessing episodic memory 3 years before diagnosis, and there were no differences between these groups on any cognitive measure. The existence of a preclinical phase in the present VaD cases suggests that circulatory disturbance may affect cognitive performance before the occurrence of stroke that leads to clinical VaD. These results extend previous findings of similar patterns of cognitive deficits in the early clinical phases of AD and VaD to the preclinical phases of these diseases.     

Depressive symptoms, vascular risk factors, and Alzheimer's disease

BACKGROUND: Depressive symptoms in the elderly are associated with an increased Alzheimer's disease (AD) risk. We sought to determine whether the association between depressive symptoms and AD is explained by a history of vascular risk factors and stroke. METHODS: Five hundred and twenty-six elderly persons from New York City without dementia at baseline were followed for a mean of 5 years. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAM). Incident AD was ascertained using standard criteria. Diabetes, hypertension, heart disease, current smoking and stroke were ascertained by self-report. Proportional hazards regression was used to relate HAM scores to incident AD. RESULTS: HAM scores were higher in persons with hypertension, heart disease, and stroke, which in turn were related to higher AD risk. AD risk increased with increasing HAM scores as a continuous logarithmically transformed variable (HR for one point increase = 1.4; 95% CI = 1.1,1.8) and as a categorical variable (HR for HAM >/= 10 = 3.4; 95% CI = 1.5,8.1; p for trend = 0.004 with HAM = 0 as the reference). These results were virtually unchanged after adjustment for vascular risk factors and stroke, individually (HR for HAM >/= 10 = 3.4; 95% CI = 1.5,8.1; p for trend = 0.004), and in a composite measure (HR for HAM >/= 10 = 3.0; 95% CI = 1.2,7.8; p for trend = 0.02). CONCLUSION: The prospective relation between depressive symptoms and AD is not explained by a history of vascular risk factors and stroke, suggesting that other mechanisms may account for this association. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Stroke and the risk of Alzheimer disease

BACKGROUND: Alzheimer disease (AD) and stroke are common in elderly individuals, but the relation between these 2 disorders remains uncertain. OBJECTIVE: To investigate the association between a clinical history of stroke and subsequent risk of AD. DESIGN: A cohort of 1766 Medicare recipients without dementia participated in a longitudinal follow-up study from 1992 through 1999 in upper Manhattan, New York, NY. History of stroke and presence of cardiovascular risk factors were ascertained at the onset of the study. Incidence rates for AD among those with and without stroke were calculated; proportional hazards ratios were computed using age at onset of the disease as the time-to-event variable. RESULTS: The annual incidence for AD was 5.2% among individuals with stroke vs 4% for those without stroke. The hazards ratio for AD among those with a history of stroke was 1.6 (95% confidence interval, 1.0-2.4) compared with those without stroke. Of the vascular risk factors, hypertension, diabetes, and heart disease, only diabetes related to risk of AD in the absence of stroke. Stroke remained weakly associated with AD in the absence of these factors, but risk significantly increased with the additional factors of hypertension (relative risk, 2.3; 95% confidence interval, 1.4-3.6), diabetes (relative risk, 4.6; 95% confidence interval, 2.2-9.5), or heart disease (relative risk, 2.0; 95% confidence interval, 1.2-3.2). CONCLUSIONS: Stroke is associated with AD among elderly individuals. The relation is strongest in the presence of known vascular risk factors. The observed association between stroke and AD might relate to an underlying systemic vascular disease process, or alternatively, to the additive effects of stroke and AD pathologic features, leading to an earlier age at onset of disease.     

Early symptoms and signs of cognitive deficits might not always be detectable in persons who develop Alzheimer's disease

OBJECTIVE:Clinical syndromes such as amnestic mild cognitive impairment (MCI) are highly predictive of future development of Alzheimer's disease (AD), but it is not known how many of the individuals that develop the disease can be identified with these syndromes. This study aims to determine how many individuals with AD show detectable symptoms or clinical signs of cognitive deficits three years before diagnosis.METHODS: 152 incident AD cases were identified in a dementia-free cohort of 1417 persons aged 75-95, after three-year follow-up from a prospective population-based study, the Kungsholmen Project. Symptoms of cognitive impairment including the subjective report of memory problems, and cognitive deficits were objectively measured with an extensive neuropsychological test battery at baseline. Incident AD was clinically diagnosed according to DSM-IIIR criteria at three-year follow-up.RESULTS: Only half of future AD cases reported subjective memory problems three years before diagnosis. More than one-third of incident AD cases did not exhibit detectable deficits in any of the investigated specific cognitive domains. Only 38.3% had both subjective complaints and domain-specific cognitive deficits.CONCLUSIONS: Symptoms and signs currently used to define MCI are not always present in persons who develop AD. Increasing the number of potentially identifiable and treatable preclinical AD cases is unfeasible unless more sensitive subjective and objective markers are identified. Furthermore, as only half of future AD cases report subjective memory problems three years before diagnosis, the number of persons coming to the attention of medical care is limited.     

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.     

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.     

Interaction between vascular factors and the APOE ε4 allele in predicting rate of progression in Alzheimer's disease

Vascular factors have been shown to affect the rate of Alzheimer's disease (AD) progression. However, the effect of the APOE ε4 allele on rate of progression has been ambiguous. Little research to date has examined an interaction between vascular factors and the APOE ε4 allele in predicting decline among AD patients. 216 participants with incident AD from a population of elderly persons in Cache County, Utah, were followed for a mean of 3.3 years and 4.2 follow-up visits. A history of vascular risk factors and conditions and anti-hypertensive use was assessed at the diagnostic visit. Linear mixed effects models tested interactions between the vascular factors, APOE ε4, and time as predictors of clinical progression on the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB). Multiple comparisons were corrected using the Holm-Bonferroni method. There was a 3-way interaction between stroke, APOE ε4 and time in predicting MMSE decline (LR χ2 = 10.32, 2 df, p = 0.006). For the CDR-SB, there were 3-way interactions between the APOE ε4, time and either myocardial infarction (LR χ2 = 17.83, 2 df, p = 0.0001) or stroke (LR χ2 = 11.48, 2 df, p = 0.003. Results suggest a complex relationship between the APOE ε4 and vascular factors in predicting cognitive and functional progression. Among individuals with a history of stroke or myocardial infarction at baseline, progression of AD is influenced by APOE ε4 carrier status and varies by time after AD diagnosis.     

Neuropsychological predictors of incident dementia in patients with vascular cognitive impairment,without dementia

BACKGROUND: Vascular cognitive impairment that does not fulfill dementia criteria (ie, vascular cognitive impairment, no dementia [CIND]) is common. Although progression to dementia is frequent, little is known about factors that predict progression. We examined whether performance on neuropsychological tests administered at baseline could predict incident cases of dementia in patients with vascular CIND after 5 years. Summary of Report- The Canadian Study of Health and Aging is a prospective, cohort study of 10 263 randomly selected persons aged > or =65 years. Of 149 people diagnosed with vascular CIND, 125 completed a battery of neuropsychological tests at baseline. Follow-up cognitive diagnoses were available for 102 individuals. After 5 years, 45 patients (44%) developed dementia. Low baseline scores on tests of memory and category fluency were associated with incident dementia. CONCLUSIONS: Neuropsychological measures can indicate risk of dementia in patients with vascular CIND. This study did not suggest a prediction-to-progression profile distinct from that seen in Alzheimer disease.     

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.     

Autopsy-confirmed Alzheimer's disease versus clinically diagnosed Alzheimer's disease in the Cache County Study on Memory and Aging: a comparison of quantitative MRI and neuropsychological findings

Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically diagnosed using the same antemortem criteria will provide further evidence of the utility and accuracy of neuropsychological assessments at the time of diagnosis, as well as the efficacy of quantitative magnetic resonance imaging (qMRI) in demonstrating gross neuropathological changes associated with the disease. The Cache County Study of Aging provides a unique opportunity to determine how closely AD subjects with only the clinical diagnosis match similarly diagnosed AD subjects but with postmortem confirmation of the disease. qMRI volumes of various brain structures, as well as neuropsychological outcome measures from an expanded battery, were obtained in 31 autopsy-confirmed AD subjects and 45 clinically diagnosed AD subjects. Of the various qMRI variables examined, only total temporal lobe volume was different, where those with postmortem confirmation had reduced volume. No significant differences between the two groups were found with any of the neuropsychological outcome measures. These findings confirm the similarity in neuroimaging and neuropsychological assessment findings between those with just the clinical diagnosis of AD and those with an autopsy-confirmed diagnosis in the moderate-to-severe stage of the disease at the time of diagnosis.     

Cognitive and functional decline in African Americans with VaD, AD, and stroke without dementia.

OBJECTIVE: To compare the rates of cognitive and functional decline in African American patients diagnosed at baseline with vascular dementia (VaD) (n = 79), AD (n = 113), or stroke without dementia (SWD) (n = 56) and followed for up to 7 years with annual neuropsychological and other examinations. METHODS: Study patients were diagnosed using established criteria for dementia and were administered cognitive screening, functional screening, and neuropsychological measures. Baseline dementia severity was rated using the Clinical Dementia Rating Scale. Random effects modeling was used to examine rates of decline and to compare the rates of decline in the three groups. RESULTS: Both patients with VaD and those with AD showed significant cognitive and functional decline during follow-up; patients with VaD declined at a slower rate than patients with AD; and patients diagnosed with SWD at baseline did not show cognitive or functional decline during follow-up. CONCLUSIONS: Patients with VaD decline at a slower rate than patients with AD. Patients who do not meet criteria for dementia soon after stroke may not be at high risk for developing dementia. Future studies are needed to follow VaD patients with longitudinal, specialized MR protocols, concurrent neuropsychological examinations, and neuropathologic examination to determine possible neuroimaging predictors of progressive cognitive and functional decline and to assess the contribution of Alzheimer's pathology to decline in patients diagnosed with VaD.     

Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease

Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). MCI patients experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. An issue currently under investigation is whether MCI represents the preclinical stages of AD or a distinct and static cognitive aetiology. In an attempt to address this issue, the present investigations are adopting a convergent approach to the detection of preclinical AD, where multiple risk factors are considered when making a diagnosis. Currently, one of the most important tools when assessing early cognitive changes is neuropsychological evaluation. MCI subjects typically record neuropsychological performance between that of healthy older individuals and demented patients. Tests assessing new learning, delayed recall and attention/executive function seem to provide valuable information for screening and diagnosis of MCI and early AD if interpreted properly. Recommendations concerning methodological issues and the early management of neuropsychological MCI studies were made.     

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group

OBJECTIVE: To study the difference in risk for dementing diseases between men and women. BACKGROUND: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. METHODS: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. RESULTS: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). CONCLUSION: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.     

APOE genotype,memory test performance,and the risk of Alzheimer's disease in the Canadian Study of Health and Aging

OBJECTIVES: This study examined the relation between two risks for Alzheimer's disease (AD): the apolipoprotein (APOE) epsilon4 allele and poor memory test performance. METHODS: In the Canadian Study of Health and Aging (CSHA), a 5-year longitudinal population-based study that screened and followed over 10,000 participants, 2,914 had an initial clinical assessment and 1,624 had APOE genotype testing. All participants were categorized as having no cognitive impairment, cognitive impairment but no dementia, or dementia at both baseline and follow-up. We examined those (n = 209) with a complete neuropsychological assessment at baseline and no evidence of cognitive impairment who had either APOE epsilon3/epsilon3 or epsilon3/epsilon4 genotypes and who had a clinical consensus diagnosis of either no cognitive impairment or AD at follow-up. Delayed free recall memory was evaluated at CSHA-1 with the Buschke Cued Recall Test (BCRT). RESULTS: The risk of AD at follow-up was increased for participants with an APOE epsilon3/epsilon4 genotype when memory test performance was not considered, but logistic regression demonstrated that a model which also considered baseline memory test performance was more predictive of AD. In the more complete model, reduced BCRT free recall scores were associated with an increased risk of AD, whereas the risk associated with the APOE epsilon3/epsilon4 genotype was no longer significant. CONCLUSIONS: For those with no evidence of cognitive impairment, drawn from a population-based sample of elderly persons, the APOE epsilon3/epsilon4 genotype was only associated with an increased risk of AD after 5 years if their memory test performance was relatively poor at baseline. Regardless of the APOE genotype, and in the absence of clinical evidence of cognitive impairment, reduced scores on a test of delayed free recall at baseline was associated with an increased risk of AD after 5 years.     

Preclinical memory decline in cognitively normal apolipoprotein E-epsilon4 homozygotes.

OBJECTIVE: To determine, in a cross-sectional evaluation of nondemented individuals, if age-related memory decline is influenced by apolipoprotein E (apoE) genotype. BACKGROUND: The apoE-4 allele is an important risk factor for AD. PET in cognitively normal apoE-4 carriers (mean age, 56 years) shows reduced cerebral metabolism suggestive of very early AD that precedes clinically evident memory loss or MRI-based hippocampal atrophy. METHODS: Tests of immediate and delayed recall (primary outcome measures) and other neuropsychological measures (secondary outcome measures) were given to three genetically defined groups of cognitively normal individuals (age, 49 to 69 years) including apoE-4 homozygotes (n = 25), apoE-4 heterozygotes (n = 25, all epsilon3/4), and apoE-4 noncarriers (n = 50). Groups were matched for age, gender, and educational background. Cross-sectional comparisons between the genetic subgroups of the relationship between age and test score were performed for each neuropsychological measure. RESULTS: There were no intergroup differences in mean scores on any neuropsychological measure, but tests sensitive to immediate and delayed recall showed a significant negative correlation with age in the apoE-4 homozygote group relative to the noncarrier group. CONCLUSION: Consistent with previous neuropsychological studies of early AD, this cross-sectional study suggests that age-related memory decline occurs earlier in cognitively healthy apoE-4 homozygotes than in apoE-4 heterozygotes and noncarriers, and precedes clinically detectable AD.     

The Framingham Brain Donation Program: neuropathology along the cognitive continuum

The Framingham Heart Study has enrolled 3 generations of participants, the original cohort (gen 1) enrolled in 1948, the offspring cohort (gen 2) enrolled in 1971 and the third generation enrolled in 2002. Participants have been undergoing prospective surveillance for incident stroke and dementia and embedded within this cohort is the voluntary Framingham Brain Donation Program that was begun in 1997. Participants who register to become brain donors have had one or more brain MR and cognitive test batteries administered. In addition, they undergo neurological evaluation as indicated, record review and post-mortem next-of-kin interview to determine the presence, type and extent of antemortem, clinical neurological diagnoses and to assign a retrospective clinical dementia rating (CDR) Scale score. Between 1997 and 2009 there were 1806 deaths, 186 of which were among registered brain donors and of these 139 brains could be examined. 58% were deemed cognitively normal at death. We present results for 3 projects; the first was to examine the sensitivity and specificity of our clinical diagnosis against the gold standard of pathological AD in 59 persons who underwent detailed cognitive assessment in the two years prior to death; we observed a 77.3% sensitivity (2 persons with AD were diagnosed clinically as Lewy body dementia) and a 91.9% specificity. The second examined the correlation of regional Alzheimer-type pathology to cognitive status at death among 34 persons who were over the age of 75 and without any significant vascular or alternative neurodegenerative pathology and found that neurofibrillary tangle counts distinguished between persons who were controls, had mild cognitive impairment, mild or moderate dementia; tangles in dorsolateral frontal cortex best distinguished MCI and controls. The third project examined the extent and severity of vascular pathology, again in a larger sample of varying cognitive abilities and in a subsample of persons with either amnestic or nonamnestic MCI. We observed that an aggregate ischemic injury score was significantly higher in persons with a CDR score of 0.5 than in normal controls.     

Cerebrovascular risk factors and incident depression in community-dwelling elderly

Objective: The ‘vascular depression’ hypothesis suggests that late‐life depression results from vascular brain damage. We studied the longitudinal association between cerebrovascular risk factors and incident depression in a large population‐based study. Method: Two thousand nine hundred and thirty‐one persons with the age of ≥61 years were followed up. Data on a comprehensive set of cerebrovascular risk factors were collected at baseline. Participants received a psychiatric assessment 5 years later to establish DSM‐IV diagnoses. Results: Only current smoking and antihypertensive drug use were independently associated with incident depressive symptoms. Diabetes mellitus and the Framingham stroke risk score were related to incident depressive disorder. No relation with depression was observed for cholesterol, diastolic and systolic blood pressure, history of cardiovascular disease, atrial fibrillation, left ventricular hypertrophy or the use of statins and anticoagulants. Conclusion: These results moderately support the ‘vascular depression’ hypothesis.     

Differential prediction of vascular dementia and Alzheimer’s disease in nondemented older adults within 5 years of initial testing

ObjectiveTo determine whether neuropsychological tests and the Hachinski Ischemic Score (HIS) can differentiate incident vascular dementia (VaD) from Alzheimer’s disease (AD) in nondemented older adults within 5 years of initial testing.MethodsThe Canadian Study of Health and Aging (CSHA) included three waves: CSHA-1 (1991–1992), CSHA-2 (1996–1997), and CSHA-3 (2001–2002). This analysis included participants of the CSHA who (a) underwent neuropsychological testing and clinical assessment at CSHA-2 and were determined to be nondemented, and (b) underwent diagnostic assessment at CSHA-3. The outcome measure was CSHA-3 diagnosis, classified as VaD (n = 22), probable or possible AD (n = 65), and all other diagnostic outcomes (n = 417). CSHA-3 diagnosticians were blinded to CSHA-2 test scores and diagnoses. Multinomial logistic regression with forward selection was used to determine the ability of the HIS and 15 CSHA-2 neuropsychological tests to predict CSHA-3 diagnostic outcome. The analysis was repeated after removing 15 AD cases with coexisting vascular disease.ResultsThe HIS and four neuropsychological tests were significant predictors of CSHA-3 diagnostic outcome (χ² (14) = 149.59, P < .001, R² = 0.38). Relative to developing VaD, higher HIS (odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.57–0.86) and Rey Auditory Verbal Learning Test immediate verbal recall scores (OR: 0.77; 95% CI: 0.62–0.97) were associated with lowered odds of developing AD, whereas higher phonemic fluency scores (OR: 1.21; 95% CI: 1.02–1.17) were associated with increased odds of developing AD. Removing AD cases with vascular disease did not affect results.ConclusionsIn an epidemiological sample of nondemented participants, the HIS and two neuropsychological tests contributed to the differential prediction of VaD and AD within 5 years of initial measurement.     

Frequency and clinical determinants of dementia after ischemic stroke

OBJECTIVE: To investigate the frequency and clinical determinants of dementia after ischemic stroke. METHODS: The authors administered neurologic, neuropsychological, and functional assessments to 453 patients (age 72.0 +/- 8.3 years) 3 months after ischemic stroke. They diagnosed dementia using modified Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. RESULTS: The authors diagnosed dementia in 119 of the 453 patients (26.3%). Regarding dementia subtypes, 68 of the 119 patients (57.1%) were diagnosed with vascular dementia, 46 patients (38.7%) were diagnosed with AD with concomitant stroke, and 5 patients (4.2%) had dementia for other reasons. Logistic regression suggested that dementia was associated with a major hemispheral stroke syndrome (OR 3.0), left hemisphere (OR 2.1) and right hemisphere (OR 1.8) infarct locations versus brainstem/cerebellar locations, infarcts in the pooled anterior and posterior cerebral artery territories versus infarcts in other vascular territories (OR 1.7), diabetes mellitus (OR 1.8), prior stroke (OR 1.7), age 80 years or older (OR 12.7) and 70 to 79 years (OR 3.9) versus 60 to 69 years, 8 or fewer years of education (OR 4.1) and 9 to 12 years of education (OR 3.0) versus 13 or more years of education, black race (OR 2.6) and Hispanic ethnicity (OR 3.1) versus white race, and northern Manhattan residence (OR 1.6). CONCLUSIONS: Dementia is frequent after ischemic stroke, occurring in one-fourth of the elderly patients in the authors' cohort. The clinical determinants of dementia include the location and severity of the presenting stroke, vascular risk factors such as diabetes mellitus and prior stroke, and host characteristics such as older age, fewer years of education, and nonwhite race/ethnicity. The results also suggest that concomitant AD plays an etiologic role in approximately one-third of cases of dementia after stroke.     

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.