Reproductive period and preclinical cerebrospinal fluid markers for Alzheimer disease: a 25-year study.

Jenna Najar,Anna Zettergren,Ingmar Skoog,Madeleine Mellqvist Fässberg,Lena Johansson,Tore Hällström,Silke Kern,Kaj Blennow,Henrik Zetterberg,Erik Joas

doi:10.1097/gme.0000000000001816

Abstract

Objective:The aim of the study was to examine the association between reproductive period, as an indicator of endogenous estrogen, and levels of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD).Methods:A population-based sample of women from Gothenburg, Sweden was followed from 1968 to 1994 (N = 75). All women had natural menopause and were free from dementia. Information on reproductive period (age at menarche to age at menopause) was obtained from interviews from 1968 to 1980. Lumbar puncture was performed from 1992 to 1994 and CSF levels of Aβ42, Aβ40, P-tau, and T-tau were measured with immunochemical methods. Linear regression models adjusted for potential confounders were used to analyze the relationship between reproductive period and CSF biomarkers for AD.Results:Longer reproductive period was associated with lower levels of Aβ42 (β = −19.2, P = 0.01), higher levels of P-tau (β = 0.03, P = 0.01), and lower ratio of Aβ42/Aβ40 (β = −0.02, P = 0.01), while no association was observed for T-tau (β = 0.01, P = 0.46). In separate analyses, examining the different components of reproductive period, earlier age at menarche was associated higher levels of P-tau (β = −0.07, P = 0.031) and lower ratio of Aβ42/Aβ40 (β = 0.05, P = 0.021), whereas no association was observed with Aβ42 (β = 31.1, P = 0.11) and T-tau (β = −0.001, P = 0.98). Furthermore, no association was observed between age at menopause and CSF biomarkers for AD.Conclusions:Our findings suggest that longer exposure to endogenous estrogen may be associated with increased levels of AD biomarkers in the preclinical phase of AD. These findings, however, need to be confirmed in larger samples.Video Summary:.

Highlights

Our findings suggest that longer exposure to endogenous estrogen may be associated with increased levels of Alzheimer disease (AD) biomarkers in the preclinical phase of AD
In separate analyses, examining the different components of reproductive period in crude models adjusted for birth year, earlier age at menarche was associated with higher levels of Ptau (b 1⁄4 À0.07, and P 1⁄4 0.031) and lower ratio of amyloid-b 1-42 (Ab42)/ amyloid-b 1-40 (Ab40) (b 1⁄4 0.05, and P 1⁄4 0.021), whereas no association was observed with Ab42 (b 1⁄4 31.1, and P 1⁄4 0.11) and total tau (T-tau) (b 1⁄4 À0.001, and P 1⁄4 0.98)
No association was observed between age at menopause and cerebrospinal fluid (CSF) biomarkers for AD (Ab42: b 1⁄4 À12.0, and P 1⁄4 0.13, P-tau: b 1⁄4 0.01, and P 1⁄4 0.25, T-tau: b 1⁄4 0.01, and P 1⁄4 0.49, Ab42/Ab40: b 1⁄4 À0.02, and P 1⁄4 0.058)

Summary

Methods

Study population As part of the Gothenburg H70 Birth Cohort Studies, we examined levels of CSF biomarkers for AD in the Prospective Population Study of Women from Gothenburg, Sweden. From 1968 to 1969, 1,462 women (participation rate 90%) born in 1908, 1914, 1918, 1922, and 1930 (mean age 46 years). 1100 Menopause, Vol 28, No 10, 2021 participated in a health examination.[33] The women were systematically selected from the Swedish Population Registry based on specific birth dates to yield a representative sample at the ages studied.[33] Re-examinations occurred from 1974 to 1975, 1980 to 1981, and 1992 to 1994, as described in more detail previously.[22,34]. In the follow-up from 1992 to 1994, women aged 70 years or older (ie, born 1908, 1914, 1918, and 1922) were invited to an extensive neuropsychiatric examination (n 1⁄4 590 women, participation rate 68%), and 88 consented to a lumbar puncture (LP).

Results

Discussion

Conclusion