Аннотация:About 30% of older individuals meeting neuropathologic criteria for Alzheimer's disease at autopsy are not demented during life. We investigated factors protecting against dementia among 331 women from the Nun Study, all of whom had a high or intermediate likelihood of neuropathologic AD according to Reagan criteria. We also examined the risk for dementia when 1, 2 or 3 protective factors were present at the same time. Neuropathologic examinations and diagnoses were performed masked to clinical diagnoses. The clinical records of women who died were examined to see if they met dementia criteria at death. Analyses included t-tests, chi square and multivariable logistic regression. Among women meeting AD neuropathologic criteria, 219 were demented and 113 were not demented during life. Women who were not demented were younger (89.7 vs. 91.3, p=0.004), had higher education (22.5% vs. 8.9% ≥16 years, p=0.002), larger brain weights ≥1100 g (43% vs. 25%, p<0.002), and fewer lacunar and large infarcts (30% vs. 46.5%, p=0.006). There was no difference in the presence of microinfarcts in the two groups. All variables remained significant upon logistic multivariable regression, except that low education was marginally non-significant (p=0.053) when brain weight entered the model. Odds Ratios for dementia corresponding to the number of protective factors were, for 1 (n=114): OR=0.39 (95% CI = 0.22-0.70); for 2 (n=69): OR=0.32 (95% CI =0.16-0.64) and for 3 (n=14): OR=0.08 (95% CI = 0.01-0.69) (p for trend<0.0001). Among those with 2 protective factors, the combination of higher education and larger brain weight (OR=0.28, 95% CI = 0.09-0.89), but not the other two combinations (larger brain weight and infarcts or higher education and infarcts), was significant. Protective factors related to reserve strongly predicted who remained non-demented. The level of protection increased significantly with the number of protective factors present.
