Abstract
ObjectiveTo determine whether amyloid deposition is associated with impaired neuropsychological (NP) performance and whether cognitive reserve (CR) modifies this association.MethodsIn 66 normal elderly controls and 17 patients with Alzheimer disease (AD), we related brain retention of Pittsburgh Compound B (PiB) to NP performance and evaluated the impact of CR using education and American National Adult Reading Test intelligence quotient as proposed proxies.ResultsWe found in the combined sample of subjects that PiB retention in the precuneus was inversely related to NP performance, especially in tests of memory function, but also in tests of working memory, semantic processing, language, and visuospatial perception. CR significantly modified the relationship, such that at progressively higher levels of CR, increased amyloid deposition was less or not at all associated with poorer neuropsychological performance. In a subsample of normal controls, both the main effect of amyloid deposition of worse memory performance and the interaction with CR were replicated using a particularly challenging memory test.InterpretationAmyloid deposition is associated with lower cognitive performance both in AD patients and in the normal elderly, but the association is modified by CR, suggesting that CR may be protective against amyloid-related cognitive impairment. ANN NEUROL 2010;67:353–364
Highlights
Association of Precuneus Amyloid Deposition and NP Performance as Modified by cognitive reserve (CR) across All Subjects (n؍83) We initially explored whether precuneus Pittsburgh Compound B (PiB) retention was associated with impaired NP performance using a canonical correlation analysis across both normal subjects and patients with Alzheimer disease (AD)
The canonical correlation analysis of the set of 11 NP tests versus the set of predictors revealed 2 canonical correlations that were individually significant ( p Ͻ 0.001) and of about equal strength. (Because some variables were non-normally distributed in violation of test assumptions, the statistical significance of all relevant canonical correlations in this study were confirmed with nonparametric permutation tests of 1,000 resamples, all of which returned p Ͻ 0.003.) The first pair of canonical variates had weaker loadings on the NP tests, whereas the second pair of canonical variates were loaded moderately to highly on all of the NP tests
We report that amyloid deposition is associated with reduced cognitive performance among clinically normal individuals (CDR ϭ 0), and that the relationship is systematically weaker in subjects with higher CR
Summary
To determine whether amyloid deposition is associated with impaired neuropsychological (NP) performance and whether cognitive reserve (CR) modifies this association. ANNALS of Neurology sition may show subtle signs of cognitive change if amyloid-beta deposition marks an early stage of pathophysiological change One of these potentially mediating factors is cognitive reserve (CR), which we refer to as a broad concept conferring a reduced susceptibility to impairment due to individual characteristics such as increased synaptic or neuronal capacity,[24,25] greater efficiency engaging brain networks, or the use of alternative strategies.[26,27,28] We hypothesize that these mechanisms mediating why some individuals better tolerate disease burden likely arise from multiple factors. We evaluated PiB retention as a continuous variable across wide ranges of amyloid burden and cognitive function, including normal subjects and patients with mild AD, and explored both education and an estimate of ability level (American National Adult Reading Test [AMNART] intelligence quotient [IQ]) as proxies of CR
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