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Longitudinal increases in neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels are associated with incident cognitive impairment and cognitive decline among patients with type 2 diabetes (T2D) with overweight or obesity, according to study findings published in JAMA Network Open.
Most research into the relationship between blood-based biomarkers and cognitive status have been conducted among relatively healthy patient populations.
To assess the relevance of blood-based biomarkers for cognitive outcomes among patients with T2D and overweight or obesity, investigators from Wake Forest University School of Medicine sourced data from the Look Action for Health in Diabetes (AHEAD; ClinicalTrials.gov Identifier: NCT00017953) study, which was a randomized clinical trial of a 10-year intensive lifestyle intervention, launched between 2001 and 2004. The subset of Look AHEAD participants (n=758) who underwent cognitive assessments in 2013 to 2014 and 2018 to 2020 were evaluated for the association between cognitive impairment and the change in NfL, GFAP, phosphorylated tau 181 (pTau-181), amyloid-β (Aβ)40, Aβ42, and Aβ42/40 ratio from baseline to 8 to 12 years.
Among the study population, who had a mean (SD) age of 61.5 (6.1) years and BMI of 34.8 (5.3) kg/m2, 67.4% were White, 55.9% were women 25.4% had attended less than 13 years of education, and 22.7% were apolipoprotein E (APOE) e4 carriers.
At follow-up, 297 individuals had cognitive impairment. The change in the composite cognitive score was not associated with baseline biomarker levels. However, the longitudinal change in GFAP (β, -0.087; P <.001) and NfL (β, -0.032; P =.01) were associated with the cognitive decline.
Similarly, mild cognitive impairment or probable dementia at follow-up was not associated with any biomarker at baseline but was associated with the change in GFAP (adjusted odds ratio [aOR], 1.25; 95% CI, 1.10-1.42; P =.001) and NfL (aOR, 1.10; 95% CI, 1.03-1.18; P =.008).
In interaction analyses, increasing plasma pTau-181 levels were associated with risk for cognitive impairment at follow-up among those with an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73 m2 (aOR, 0.75; 95% CI, 0.62-0.93 per pg/dL increase) but not among those with higher eGFR (aOR, 1.05; 95% CI, 0.86-1.26 per pg/dL increase).
The major limitation of this study was the lack of a cognitive assessment at baseline.
The study authors concluded, “Increasing levels of plasma NfL and GFAP among older adults with diabetes and overweight or obesity may be indicative of worsening cognition.”
Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
This article originally appeared on Endocrinology Advisor
