The Association Between Homocysteine and Memory in Older Adults

Article type: Research Article

Authors: Nelson, Monica E.^{a; *} | Andel, Ross^{a; b; c} | Nedelska, Zuzana^{b; c} | Martinkova, Julie^b | Cechova, Katerina^{b; c} | Markova, Hana^{b; c} | Matuskova, Veronika^{b; c} | Nikolai, Tomas^{b; c} | Lerch, Ondrej^{b; c} | Parizkova, Martina^{b; c} | Laczo, Jan^{b; c} | Vyhnalek, Martin^{b; c} | Hort, Jakub^{b; c}

Affiliations: [a] School of Aging Studies, University of South Florida, Tampa, FL, USA | [b] Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic | [c] International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic

Correspondence: [*] Correspondence to: Monica E. Nelson, MA, 13301 Bruce B. Downs Blvd., MHC 1317, Tampa, FL 33612, USA. Tel.: +1 813 974 3232; E-mail: mnelson10@usf.edu.

Abstract: Background:Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. Objective:We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, total cholesterol, or triglycerides. Methods:All 204 members of the Czech Brain Aging Study with subjective cognitive decline (SCD; n = 60) or amnestic mild cognitive impairment (aMCI; n = 144) who had valid data were included. Linear regression was used, followed by conditional process modeling to examine mediation and moderation. Results:Controlling for age, sex, and education, higher homocysteine was related to poorer memory performance overall (b = –0.03, SE = 0.01, p = 0.017) and in participants with SCD (b = –0.06, SE = 0.03, p = 0.029), but less so in aMCI (b = –0.03, SE = 0.02, p = 0.074); though sensitivity analyses revealed a significant association when sample was reduced to aMCI patients with more complete cognitive data (who were also better functioning; b = –0.04, SE = 0.02, p = 0.022). Results were unchanged in fully adjusted models. Neither mediation by markers of brain integrity nor moderation by APOE ɛ4, B vitamins, creatinine, and cardiovascular factors were significant. Memory sub-analyses revealed that results for SCD were likely driven by non-verbal memory. The homocysteine-memory relationship was significant when hippocampal volume was below the median (b = –0.04, SE = 0.02, p = 0.046), but not at/above the median (p = 0.247). Conclusion:Higher homocysteine levels may adversely influence memory performance, which appears particularly apparent in those without cognitive impairment. Results appear to be independent of brain health, suggesting that homocysteine may represent a good target for intervention.

Keywords: Hippocampus, magnetic resonance imaging, mild cognitive impairment, neuropsychological tests

DOI: 10.3233/JAD-201558

Journal: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 413-426, 2021