ROLE OF RESERVE IN REDUCING DEMENTIA: COMPARISON OF TWO LARGE CLINICOPATHOLOGIC STUDIES

Abstract

The role of reserve in reducing dementia is well recognized. To assess its role, we compared neuropathological and clinical data from two large studies, the Nun Study and the Adult Changes in Thought (ACT) study. Exploratory factor analyses of neuropathological measures and education suggested 3 factors in the Nun Study, corresponding to the severity of Alzheimer and vascular pathology and reserve (education and brain weight). The same 3 factors with one additional factor, severity of Lewy pathology, were seen in the ACT Study. Structural equation models (SEM) for dementia were constructed with latent variables representing these factors. Indicators for latent variables were included if their loadings exceeded 0.5 in the exploratory factor analyses. In both study models, the Alzheimer latent factor had 4 indicators, the vascular latent factor 3 indicators and the reserve latent factor 2 indicators. Associations of head circumference (Nun Study only) and the Alzheimer latent factor with brain weight (an indicator of reserve) were included in the SEMs in addition to a direct effect of age at death on dementia. Analyses were based on 263 autopsied nuns and 489 autopsied participants in the ACT Study. In the nuns, brain weight was significantly associated with head circumference, but not with the Alzheimer latent factor. Reserve was more strongly associated with dementia in the Nun Study with a beta of -0.73 (p<0.001) vs. the ACT study with a beta of -0.26 (p=0.016). Participants in the Nun Study (compared with female ACT participants) were 2.1 years older at death and had lower brain weights at autopsy (both p<0.0001). Demented participants in the Nun Study included a significantly greater percentage of those with low Braak stage (≤2) compared to demented participants in the ACT Study (46.6% vs. 33.8%, p < 0.001). Within the low Braak stage group, the risk of dementia was strongly related to low reserve (lower education and brain weight). While reserve plays a role in dementia at all ages, its contribution appears to be greatest at advanced ages, where dementia occurs more frequently in the presence of less Alzheimer pathology.