The effect of preclinical Alzheimer's disease on age-related changes in intelligence in cognitively normal older adults

Background: It is possible that estimates of normal age-related decline in intellectual function have been biased negatively by undetected preclinical Alzheimer's disease (AD). This prospective study aimed to determine the nature and magnitude of changes in crystallized and fluid intelligence, as well as their relationship to one another, in normal aging, taking into account the effects of preclinical AD. Methods: Cognitively normal older adults (n = 494) aged between 60 and 84 years underwent serial assessment of fluid and crystallized intelligence at 18-month intervals over 72 months and PET neuroimaging for the presence of abnormal amyloid-β (Aβ+; n = 184). The effects of age and Aβ + on changes in fluid and crystallized intelligence were analysed using linear mixed models. An intelligence discrepancy score was developed from linear regression analysis of the extent to which fluid intelligence could be predicted from crystallized intelligence. The predictive validity of the intelligence discrepancy score for Aβ status or clinical disease progression was evaluated. Results: Relative to the Aβ- group, the Aβ + group showed greater age-related decline on fluid, but not crystallized, intelligence. The intelligence discrepancy score predicted progression to clinically recognized disease (i.e., mild cognitive impairment or dementia), but was unrelated to Aβ status. Conclusions: Preclinical AD is associated with more rapid age-related decline in fluid, but not crystallized, intelligence. Accordingly, a discrepancy between fluid and crystallized intelligence does indicate risk of progression to early AD.