Alzheimer's pathology, mixed pathologies and the clinical expression of dementia in the old and the oldest old

Abstract

Recent studies have come to conflicting conclusions as to whether the relationship of Alzheimer's disease (AD) pathology and clinical dementia is the same in the oldest old as it is for persons below the age of 90. Most of these studies have not incorporated data on mixed pathologies. We assessed clinical and neuropathologic data from 638 persons aged 65-106 at death from the Rush Memory and Aging Project and the Religious Orders Study, two longitudinal studies of aging and dementia. Persons were evaluated on average 6 months prior to death using standard criteria for dementia. Brains were evaluated for a pathologic diagnosis of AD (NIA-Reagan criteria), Lewy bodies (LB) and infarcts, and whether they had one or mixed pathologies. We investigated the relationship of single and mixed pathologies and clinical dementia prior to death in persons age 90 and over compared to persons under age 90. We used logistic regression models adjusted for sex and education to test whether age at death modified the effect of pathology on the odds of dementia. There were 225 persons age 90 and over at death (mean = 94.1, SD = 3.1) and 413 persons under age 90 (mean = 83.5, SD = 4.9). The frequency of AD pathology and infarcts was higher in the oldest old compared to younger old (AD: 71.1% vs. 52.8%, p < 0.001; infarcts: 40.7% vs. 27.5%, p < 0.001). There was no significant difference between the two age groups for Lewy bodies (21.3% vs. 16.4%, p = 0.099). Mixed pathologies were present in 42.2% of the oldest-old compared to 23.1% of the old (p < 0.001). Both AD and mixed pathologies independently increased the odds of dementia in both the old and oldest old (all p-values <0.001). There was no difference in the relationship of AD or mixed pathologies to dementia in the oldest old compared to the younger old (p>0.2 for all interactions). The frequency of mixed pathologies increase with age. AD pathology, LB and infarcts all individually and in combination increase the odds of dementia in both younger and older elders. AD pathology has the same effect on clinical dementia in the old and oldest old when accounting for other pathologies.