Cerebrospinal fluid β-amyloid 1-42 concentration may predict cognitive decline in older women

Background: Low levels of cerebrospinal fluid (CSF) beta-amyloid 1-42 (A beta 42) and high total tau (T-tau) are diagnostic for manifest Alzheimer's disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people. Methods: The longitudinal relationship between CSF markers, A beta 42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (Delta MMSE) score between 1992 and 2002 were investigated in 55 women (aged 70-84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992-3. Results: Over the 8-year follow-up period, Delta MMSE (range = +3 to 221 points) was correlated with A beta 42 (Spearman's r = 0.40, p = 0.002), such that lower levels of A beta 42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman's r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of >= 5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8-year follow-up period (observed in four women), including age, education, A beta 42 and T-tau as covariates, showed that A beta 42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml A beta 42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013). Conclusions: Low levels of CSF A beta 42 may predict cognitive decline among older women without dementia.