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Cerebrospinal fluid β-amyloid 1–42 concentration may predict cognitive decline in older women
  1. Deborah R Gustafson*,
  2. Ingmar Skoog,
  3. Lars Rosengren,
  4. Henrik Zetterberg,
  5. Kaj Blennow
  1. The Institute of Neuroscience and Physiology, Section for Psychiatry and Neurochemistry, Neuropsychiatric Epidemiology Unit, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
  1. Correspondence to:
 Dr D R Gustafson
 Department of Psychiatry, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden;deb.gustafson{at}


Background: Low levels of cerebrospinal fluid (CSF) β-amyloid 1–42 (Aβ42) 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, Aβ42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (ΔMMSE) 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, ΔMMSE (range =  +3 to −21 points) was correlated with Aβ42 (Spearman’s r = 0.40, p = 0.002), such that lower levels of Aβ42 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, Aβ42 and T-tau as covariates, showed that Aβ42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Aβ42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013).

Conclusions: Low levels of CSF Aβ42 may predict cognitive decline among older women without dementia.

  • Aβ42, β-amyloid 1–42
  • AD, Alzheimer’s disease
  • CSF, cerebrospinal fluid
  • LP, lumbar puncture
  • MCI, mild cognitive impairment
  • MMSE, Mini-Mental State Examination
  • T-tau, total tau

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  • * DRG also has an appointment at the Medical College of Wisconsin, Wisconsin, USA.

  • Published Online First 10 November 2006

  • Funding: This study was supported by grants from the Swedish Research Council (grant nos 11337, 11267), the Swedish Council for Working Life and Social Research (nos 2835, 2646), the Alzheimer’s Association Stephanie B Overstreet Scholars (IIRG-00-2159) and the Alzheimer’s Association Zenith Award (ZEN-01-3151), National Institutes of Health/National Institutes on Aging 1R03AG026098 - 01A1, Stiftelsen Söderström-Königska Sjukhemmet, Stiftelsen för Gamla Tjänarinnor, Handlanden Hjalmar Svenssons Forskningsfond, Stiftelsen Professor Bror Gadelius’ Minnesfond, the Swedish Society of Medicine, the Göteborg Medical Society, Alzheimerfonden, Alma och Anna Yhlen’s Foundation, the Göteborg Medical Services and Social Services Administrations, and the Fredrik and Rosa von Malmborgs Foundation for Brain Research. The sponsors had no role in the study design, data collection, data analysis, data interpretation or writing of the report.

  • Competing interests: None declared.