Hypertension is associated with cognitive decline in elderly people at high risk for dementia.

Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in , MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.

The association of age with rate of cognitive decline in elderly individuals residing in supporting care facilities.

OBJECTIVES: This study examines the effect of age on rate of cognitive decline in different stages of dementia, of nursing home and assisted-living residents. METHODS: In this longitudinal study, the Mini Mental State Examination (MMSE) was used to measure rate of cognitive decline in subjects who were nondemented [Clinical Dementia Rating (CDR)=0; n=353], questionably demented (CDR=0.5; n=121), or frankly demented (CDR≥1; n=213) at baseline. RESULTS: A generalized estimating equation was used to model the MMSE scores over time (mean follow-up 2.9±2.0 y). The generalized estimating equation model had the MMSE scores at successive follow-up time points as dependent variables and had linear and quadratic age, follow-up time from baseline, CDR at baseline, and all the interactions among them as independent variables, controlling for MMSE at baseline, sex, race, and education. The mean age of the entire sample was 85.2±7.4 years at baseline. There were no significant interactions of linear age effects with rate of cognitive decline. The analysis of interaction of quadratic age with rate of cognitive decline showed complex relationships: in the nondemented group, there was no substantial quadratic association of age with the rate of cognitive decline (P=0.13); in the questionable demented group, the oldest subjects declined relatively faster (P=0.02); and in the demented group, the youngest and oldest subjects tended to decline relatively less than subjects in the intermediate ages (P=0.07). CONCLUSIONS: This study adds an additional aspect to the complexity of the association between age and rate of cognitive decline, showing that the direction and amplitude of this effect differs according to the stage along the course of cognitive decline.

Serum lipids are related to Alzheimer's pathology in nursing home residents.

BACKGROUND: Studies of associations between serum lipids and Alzheimer's disease (AD) or other dementias in the elderly show conflicting results, perhaps due to misclassification of the various dementias. METHODS: For 358 nursing home residents, serum lipids were studied at admission and diagnoses established at autopsy. We used defined neuropathological criteria to distinguish the presence of AD and to avoid errors of clinical dementia assessment. RESULTS: Residents with any AD pathology, as compared to those without AD pathology, had higher mean serum total cholesterol (TC; 200.4 vs. 185.9 mg/dl; p = 0.02) and higher mean low-density lipoprotein cholesterol (LDL; 124.5 vs. 111.5 mg/dl; p = 0.03). Further, mean TC, LDL and high-density lipoprotein cholesterol levels all increased progressively with increasing pathological certainty of AD (p for trend = 0.001, 0.02 and 0.02). CONCLUSIONS: TC and LDL were significantly related to pathologically defined AD. If serum lipids have a role in the pathogenesis of AD, interventions may modify the course of disease.

Corticosteroids, but not NSAIDs, are associated with less Alzheimer neuropathology.

The objective of this study was to test the hypothesis that corticosteroid and nonsteroidal anti-inflammatory drug (NSAID) medications are associated with less global and regional Alzheimer's disease (AD) neuropathology. This postmortem study was based on 694 brains of subjects from the Mount Sinai School of Medicine Brain Bank who did not have neuropathologies other than neuritic plaques (NPs), neurofibrillary tangles (NFTs), or cerebrovascular disease. Densities of NPs and of NFTs were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Counts of NPs in several neocortical regions were also assessed. For each neuropathology measure, analyses of covariance controlling for age at death and sex compared subjects who received only corticosteroids (n = 54) or those who received only NSAIDs (n = 56) to the same comparison group, subjects who received neither (n = 576). Subjects receiving corticosteroids had significantly lower ratings and counts of NPs for all neuropathological measures, and NFTs overall and in the cerebral cortex and amygdala. In contrast, no measures were significant for subjects who received NSAIDs. Use of corticosteroids was associated with approximately 50% fewer NPs and NFTs in most brain regions examined, compared with nonmedicated subjects. In contrast, use of NSAIDs was not substantially associated with the reductions in hallmark lesions of AD. Because corticosteroids have anti-inflammatory as well as a myriad of other neurobiological effects, more direct studies in model systems could reveal novel therapeutic targets and mechanisms for AD lesion reduction.

Role of the neuropathology of Alzheimer disease in dementia in the oldest-old.

BACKGROUND: Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old. OBJECTIVE: To assess the relationship between estimates of cognitive function and NP and NFT pathologic conditions in 317 autopsied persons aged 60 to 107 years. DESIGN: We studied the relationship between severity of dementia and the density of these characteristic lesions of Alzheimer disease in young-old, middle-old, and oldest-old persons. The relationship of the severity of dementia as measured by the Clinical Dementia Rating scale to the density of NPs and NFTs was then assessed in each age group. PARTICIPANTS: Three hundred seventeen brains of persons aged 60 years and older were selected to have either no remarkable neuropathological lesions or only NP and NFT lesions. Brains with any other neuropathological conditions, either alone or in addition to Alzheimer disease findings, were excluded. The study cohort was then stratified into the youngest quartile (aged 60-80 years), middle 2 quartiles (aged 81-89 years), and oldest quartile (aged 90-107 years). RESULTS: While the density of NPs and NFTs rose significantly by more than 10-fold as a function of the severity of dementia in the youngest-old group, significant increases in the densities of NPs and NFTs were absent in the brains of the oldest-old. This lack of difference in the densities of NPs and NFTs was due to reduced lesion densities in the brains of oldest-old persons with dementia rather than to increased density of these lesions in the brains of nondemented oldest-old persons. CONCLUSIONS: These findings suggest that the neuropathological features of dementia in the oldest-old are not the same as those of cognitively impaired younger-old persons and compel a vigorous search for neuropathological indices of dementia in this most rapidly growing segment of the elderly population.