UC San Diego

Rationale : Differences in prevalence, age of onset, and mortality rates have been found between Hispanic and non- Hispanic older adults with Alzheimer's disease (AD). Examination of factors such as bilingualism and cultural differences in diagnostic measures is needed to improve understanding of how they may affect the diagnosis and progression of AD in Hispanic older adults. The proposed set of studies aims to elucidate the mechanisms underlying cognitive changes in Hispanics with AD. Design : In Study 1, young and older Spanish-English bilinguals were tested on language-switching and non-linguistic color-shape- switching paradigms to identify age-related changes in language control. Study 2 investigated which neuropsychological tests are predictive of progression to AD in Hispanics to better understand preclinical markers of AD in this cohort. Study 3 compared the neuropathological and neuropsychological profiles of Hispanic and non-Hispanic patients with autopsy-confirmed AD. A follow-up study (Study 4) examined four consecutive years of semantic fluency performance in a subset of decliners from Study 2 to investigate the consistency of semantic exemplar loss over time in both cultural groups. Results : Study 1 revealed subtle parallels between executive control and language control, but also some differences suggesting that language control remains relatively sheltered from aging-related decline in executive control. In Study 2, many assessment measures revealed significant disadvantages in Hispanic controls, but nevertheless predicted AD in Hispanic decliners. Conversely, some tests were not sensitive to AD in Hispanic decliners. Unexpectedly, semantic fluency revealed a cross-over interaction : Hispanic controls generated fewer correct responses than non-Hispanics, whereas Hispanic decliners outperformed non-Hispanics. In Study 3, this semantic fluency pattern emerged across many neuropsychological measures. Hispanics with AD were also found to have less AD pathology but greater neurovascular pathology than non-Hispanics. In Study 4, Hispanic decliners outperformed non-Hispanics across four years of category fluency, but groups did not differ in consistency of semantic exemplar loss. Conclusions : Findings highlight the importance of a comprehensive approach to understanding the cognitive effects of AD in Hispanics. Together, the studies provide preliminary evidence that factors such as bilingualism, vascular risk, and sociological issues may complicate interpretation of neuropsychological profiles and diagnosis of AD in Hispanics