Cognition decline after menopause transition

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Markers of mitochondrial function in perimenopausal and postmenopausal women correlate to numerous measures of cognitive performance, according to a study presented at the 2020 Virtual Annual Meeting of the North American Menopause Society (NAMS).

These measures are verbal learning, verbal memory, organizational strategies that support verbal learning and memory, verbal fluency and spatial ability.

“Evidence, largely from animal studies, suggests there is a change in mitochondrial function from the premenopause to the perimenopause, and the change is a deleterious one resulting in brain dysfunction,” said co-principal investigator Pauline Maki, PhD, a professor of psychiatry, psychology and ob/gyn at the University of Illinois at Chicago. “This change in mitochondrial function would indicate a critical change in the way that the brain generates and uses energy as women age.”

Dr. Maki and her colleagues were inspired by a 2017 study in PLOS One that identified a mitochondrial biomarker (an Alzheimer’s bioenergetic phenotype) in the brain and periphery of perimenopausal and postmenopausal women. “We wanted to expand the range of mitochondrial biomarkers in the human work,” Dr. Maki told Contemporary OB/GYN.

Co-principal investigator Pauline Maki, PhD, a professor of psychiatry, psychology and ob/gyn at the University of Illinois at Chicago.

The current MsBrain study enrolled 110 perimenopausal and postmenopausal women living in and around Pittsburgh (mean age 58.56, 77.3% White) who were assessed over the past 3 years.

The women completed a cognitive test battery, including tests of verbal learning and memory, spatial reasoning, working memory, verbal recall and global cognition.

Extracellular flux analysis was used to obtain measures of nonmitochondrial oxygen consumption, baseline respiratory rate, maximal respiratory capacity, basal glycolytic rate, proton leak, mitochondrial oxidation production, and adenosine triphosphate (ATP)-linked respiration in circulating platelets.

“We discovered a range of mitochondrial biomarkers significantly related to cognitive function in cognitively normal postmenopausal women,” Dr. Maki said. “Many of the biomarkers were related to the ability of women to use helpful strategies when learning new material.”

Higher non-mitochondrial oxygen consumption, baseline respiratory rate, maximal respiratory capacity, basal glycolytic rate, proton leak, ATP-linked respiration in circulating platelets and mitochondrial oxidant production were each associated with better performance on a range of cognitive test scores: verbal learning (P < 0.01); organizational strategies to enhance learning (P < 0.05); California Verbal Learning Test (CVLT) short delay (P < 0.05); card rotations (P < 0.05); and memory (P < 0.05).

Dr. Maki said one way to learn new material is rote or simple memorization. “But the other involves deep processing of the material,” she said. “Mitochondrial markers were notably related to the extent to which women used the more helpful of the two strategies, which is related to function of the prefrontal cortex.”

The investigators were surprised by the number of associations found between mitochondrial markers and cognition at midlife. “Our results are encouraging,” Dr. Maki said.

The cross-sectional study, however, was unable to address whether these are causal connections. “Although the findings might be related to menopause, we cannot state that, because the women in our study were postmenopausal,” she said. “We also do not know if these same relationships might also exist in men of similar ages.”

Study outcomes in general indicate that the mitochondria, which control energy production in the brain, are associated with cognitive function. “This is a new mechanism that can be targeted in future longitudinal studies to examine changes in mitochondria markers and changes in cognition through the menopause transition,” Dr. Maki said.

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Disclosures:

Dr. Maki has been a paid consultant to Pfizer, Abbvie and Balchem.