The effects of intelligence and education on the development of dementia

A number of recent epidemiological studies have shown that the prevalence and incidence of dementia are increased in population strata with low compared to high levels of education. This has been explained as a consequence of a greater 'brain reserve capacity' in people with a high level of education. Theoretically, however, brain reserve capacity is better reflected by intelligence than by level of education. Thus, the emergence of dementia will be better predicted by low pre-morbid intelligence than by low education. This prediction was tested in a population based sample of elderly subjects (N = 2063; age range 65-84; Amsterdam Study of the Elderly) who were followed over 4 years. Dementia was diagnosed using the Geriatric Mental State examination (GMS). Pre-morbid intelligence was measured using the Dutch Adult Reading Test (DART), a short reading test which gives a good estimate of verbal intelligence, and is relatively insensitive to brain dysfunction. The effects of age, gender, occupational level, number of diseases affecting the central nervous system and family history of dementia or extreme forgetfulness were also examined. Logistic regression analysis showed that low DART-IQ predicted incident dementia better than low level of education. A high occupational level (having been in charge of subordinates) had a protective effect. This result supports the brain reserve theory. It also indicates that low pre-morbid intelligence is an important risk factor for cognitive decline and dementia. Use of reading ability tests is to be preferred over years of education as estimator of pre-morbid cognitive level in (epidemiological) dementia researc

Association between memory complaints and incident Alzheimer's disease in elderly people with normal baseline cognition

In the community-based Amsterdam Study of the Elderly, a sample of 3,778 nondemented persons, 65-84 yrs old, was divided into 2 cognitive categories: normal, and borderline and impaired. At baseline, the presence or absence of memory complaints was assessed with a single question. At follow-up, incident cases of Alzheimer's disease were diagnosed in a 2-step procedure. After an average of 3.2 yrs, 2,169 persons were reevaluated, of whom 77 had incident Alzheimer's disease. Analyses showed that memory complaints were associated with incident Alzheimer's disease in Ss with normal baseline cognition but not in Ss with impaired baseline cognition. Findings suggest that memory complaints are a relatively strong predictor of incident Alzheimer's disease in older persons in whom cognitive impairment is not yet apparent. Also, they suggest that older persons may be aware of a decline in cognition at a time when mental status tests are still unable to detect a decline from premorbid functioning. (PsycINFO Database Record (c) 2002 APA, all rights reserved

Depressive symptoms and risk of Alzheimer's disease in more highly educated older people

In an earlier study we observed that a depressive syndrome was highly predictive of developing Alzheimer's disease (AD) in older persons with normal baseline cognition and higher levels of education. We interpreted these findings as the depression being an early noncognitive manifestation of AD in persons with more cognitive reserve. The present study examines whether specific symptoms of depression can be identified that predict AD among older subjects with higher levels of education. In the community-based Amsterdam Study of the Elderly (AMSTEL), a sample of 3,147 nondemented persons with normal cognition, 65 to 84 years old, was selected and divided into subjects with >8 years and 8 years and 31 with 8 years of education depressed mood and subjective bradyphrenia were strongly associated with incident AD. No association between depressive symptoms and AD was observed among subjects with <or =8 years of education. Both depressed mood and subjective bradyphrenia seem to indicate subclinical AD in older people with higher levels of education. Clinicians should be alert that in these persons, AD may become apparent within a relatively short period of tim

Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study

In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors

Higher estrogen levels are not associated with larger hippocampi and better memory performance

BACKGROUND: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. OBJECTIVE: To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance. DESIGN AND SETTING: Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia. PARTICIPANTS: Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol. MAIN OUTCOME MEASURE: Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall). RESULTS: Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewe

Aspects of the ecology of the greater bilby, Macrotis lagotis, in Queensland

AIMS: It has been suggested that in patients with type 2 diabetes mellitus (T2DM), brain atrophy is most pronounced in the hippocampus, but this has not been investigated systematically. The present pooled analysis of three studies examined if hippocampal atrophy is more prominent than global brain atrophy in patients with T2DM relative to controls. METHODS: Data were derived from a cohort study of patients with vascular disease (SMART-Medea (T2DM=120; no T2DM=502)), and from two case-control studies (UDES1 (T2DM=61; controls=30) and UDES2 (T2DM=54; controls=53)). In SMART-Medea and UDES1, hippocampal volume was obtained by manual tracing on 1.5 Tesla (T) MRI scans. Total brain and intracranial volume (ICV) were determined by an automated segmentation method. In UDES2, hippocampal and total brain volume were determined by FreeSurfer and ICV by manual segmentation on 3 T MRI scans. RESULTS: The pooled analyses, adjusted for age and sex, showed a significant negative relation between T2DM and total brain-to-ICV ratio (standardized mean difference=-1.24%, 95% CI: -1.63; -0.86), but not between T2DM and hippocampal-to-ICV ratio (0.00%, 95% CI: -0.01; 0.00) or between T2DM and hippocampal-to-total brain volume ratio (0.01%, 95% CI: -0.01; 0.02). In patients with T2DM no associations were found between brain volume measures and HbA1c or memory. CONCLUSION: Patients with T2DM had greater brain atrophy but not hippocampal atrophy, compared to controls. These findings do not support specific vulnerability of the hippocampus in patients with T2DM

Reproductive period and risk of dementia in postmenopausal women

CONTEXT: Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied. OBJECTIVE: To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause. DESIGN AND SETTING: The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands. PARTICIPANTS: A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche

Association of white matter hyperintensity markers on MRI and long-term risk of mortality and ischemic stroke the SMART-MR study

ObjectiveTo determine whether white matter hyperintensity (WMH) markers on MRI are associated with long-term risk of mortality and ischemic stroke.MethodsWe included consecutive patients with manifest arterial disease enrolled in the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study. We obtained WMH markers (volume, type, and shape) from brain MRI scans performed at baseline using an automated algorithm. During follow-up, occurrence of death and ischemic stroke was recorded. Using Cox regression, we investigated associations of WMH markers with risk of mortality and ischemic stroke, adjusting for demographics, cardiovascular risk factors, and cerebrovascular disease.ResultsWe included 999 patients (59 +/- 10 years; 79% male) with a median follow-up of 12.5 years (range 0.2-16.0 years). A greater periventricular or confluent WMH volume was independently associated with a greater risk of vascular death (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47) for a 1-unit increase in natural log-transformed WMH volume and ischemic stroke (HR 1.53, 95% CI 1.26-1.86). A confluent WMH type was independently associated with a greater risk of vascular (HR 1.89, 95% CI 1.15-3.11) and nonvascular death (HR 1.65, 95% CI 1.01-2.73) and ischemic stroke (HR 2.83, 95% CI 1.36-5.87). A more irregular shape of periventricular or confluent WMH, as expressed by an increase in concavity index, was independently associated with a greater risk of vascular (HR 1.20, 95% CI 1.05-1.38 per SD increase) and nonvascular death (HR 1.21, 95% CI 1.03-1.42) and ischemic stroke (HR 1.28, 95% CI 1.05-1.55).ConclusionsWMH volume, type, and shape are associated with long-term risk of mortality and ischemic stroke in patients with manifest arterial disease.Neuro Imaging Researc

Reduced parenchymal cerebral blood flow is associated with greater progression of brain atrophy: the SMART-MR study

Global cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 +/- 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: -0.23 to -0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: -0.29 to -0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time (p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF (p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration.Neuro Imaging Researc