Cerebrospinal fluid markers and change in MMSE score over an 8-year follow-up period - the population study of women in Gothenburg, Sweden

Abstract

Between 2010 and 2050, Alzheimer's disease (AD) willreach epidemic proportions, highlighting the importance of identifying appropriate preclinical markers for prevention. Biomarkers present in cerebrospinal fluid (CSF) may be useful for predicting progression from preclinical to clinical AD. We investigated the longitudinal relationship between cerebrospinal fluid markers - amyloid beta-42 (Abeta-42), tau, growth-associated protein-43 (GAP-43), and the CSF-to-serum albumin ratio (albumin ratio) - in relationship to dementia occurrence and change in Mini-Mental State Examination (MMSE) score over an 8-year follow-up period in a population-based sample of women. The MMSE and lumbar puncture were performed in 1992 on a representative sample of 84 women without dementia born in 1908, 1914, 1918, and 1922 (aged 70–84 years) as part of the Population Study of Women (PSW) in Göteborg, Sweden. Cerebrospinal fluid was analyzed for Abeta-42, GAP-43, tau protein, and the albumin ratio. Women were followed for 8 years after lumbar puncture for dementia occurrence and a repeat MMSE. Correlation and regression analyses and ANOVA were used to relate CSF markers, dementia, age, and change in MMSE score between 1992 and 2000. Women who developed dementia after 1992 (n=6) had a lower Abeta-42 (p=0.061) level, and higher tau (p=0.000) and GAP-43 (p=0.023) levels at baseline compared to women who did not become demented. Women who became demented also experienced a greater decline in MMSE score (p=0.000) between 1992 and 2000. Among 51 women who never developed dementia and who participated in the MMSE in 1992 and 2000, decline in MMSE score (range=3 to -8 points) was correlated with decreases in Abeta-42 (r=0.359, p=0.010). Of those experiencing a decline of at least 2 points in MMSE (n=14), mean Abeta-42 levels were lower compared to those who experienced no decline (p=0.025). In a multivariate linear regression model including all CSF markers and predicting change in MMSE, Abeta-42 was the sole predictor (R2=0.173, p=0.026). CSF Abeta-42 is a useful marker of cognitive decline as measured using the MMSE among elderly women without dementia, and CSF markers are useful predictors of dementia when measured at least one year prior to dementia onset.