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. 2017 Jan 24;88(4):371-378.
doi: 10.1212/WNL.0000000000003537. Epub 2016 Dec 16.

Long-term cortisol measures predict Alzheimer disease risk

Gilda E Ennis  1 , Yang An  1 , Susan M Resnick  1 , Luigi Ferrucci  1 , Richard J O'Brien  1 , Scott D Moffat  2
Affiliations

Long-term cortisol measures predict Alzheimer disease risk

Gilda E Ennis et al. Neurology. .

Abstract

Objective: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk.

Method: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk.

Results: UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset.

Conclusions: Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD.

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Figures

Figure
Figure. Differences in UFC/Cr level (A) and variability (B) between control and future participants with AD controlling for baseline age
*p < 0.05; error bars represent 95% confidence intervals.AD = Alzheimer disease; CV = coefficient of variation; UFC/Cr = urinary free cortisol/creatinine.
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References

    1. Armanini D, Vecchio F, Basso A, et al. . Alzheimer's disease: pathophysiological implications of measurement of plasma cortisol, plasma dehydroepiandrosterone sulfate, and lymphocytic corticosteroid receptors. Endocrine 2003;22:113–118. - PubMed
    1. Giubilei F, Patacchioli FR, Antonini G, et al. . Altered circadian cortisol secretion in Alzheimer's disease: clinical and neuroradiological aspects. J Neurosci Res 2001;66:262–265. - PubMed
    1. Näsman B, Olsson T, Fagerlund M, Eriksson S, Viitanen M, Carlström K. Blunted adrenocorticotropin and increased adrenal steroid response to human corticotropin-releasing hormone in Alzheimer's disease. Biol Psychiatry 1996;39:311–318. - PubMed
    1. Umegaki H, Ikari H, Nakahata H, et al. . Plasma cortisol levels in elderly female subjects with Alzheimer's disease: a cross-sectional and longitudinal study. Brain Res 2000;881:241–243. - PubMed
    1. Weiner M, Vobach S, Olsson K, Svetlik D, Risser RC. Cortisol secretion and Alzheimer's disease progression. Biol Psychiatry 1997;42:1030–1038. - PubMed

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