Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

PubMed ID: 36114981

Author(s): Schubert CR, Fischer ME, Pinto AA, Paulsen AJ, Chen Y, Huang GH, Klein BEK, Tsai MY, Merten N, Cruickshanks KJ. Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife. Neurol Sci. 2023 Jan;44(1):149-157. doi: 10.1007/s10072-022-06386-0. Epub 2022 Sep 17. PMID 36114981

Journal: Neurological Sciences : Official Journal Of The Italian Neurological Society And Of The Italian Society Of Clinical Neurophysiology, Volume 44, Issue 1, Jan 2023

BACKGROUND Age-related declines in cognitive function may begin in midlife.

PURPOSE To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment.

METHODS Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors.

RESULTS Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/μL) were associated with 5-year cognitive decline.

CONCLUSIONS Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.