Association between Peripheral Immune-inflammatory Biomarkers and Response to Cognitive Rehabilitation in Early Alzheimer Disease

Abstract

This prospective single-arm study examined associations between peripheral immune-inflammatory biomarkers and changes observed during cognitive rehabilitation in patients with early Alzheimer disease.

Seventy-two patients completed a 12-week structured cognitive rehabilitation program delivered three times weekly. Baseline plasma/serum glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured. Cognitive and functional outcomes were assessed before and after the program. Correlation and multivariable linear regression analyses examined associations between baseline biomarkers and pre–post changes.

After 12 weeks, scores on global cognition, memory, digit span, and semantic fluency increased, whereas Trail Making Test completion times and Activities of Daily Living dependency scores decreased. Among 60 participants with repeat biomarker measurements, GFAP, IL-6, TNF-α, and CRP levels were lower at follow-up. Baseline GFAP, IL-6, TNF-α, and CRP were inversely correlated with change in Montreal Cognitive Assessment score; GFAP showed the strongest correlation (r=−0.48). After adjustment for age, education, and baseline cognition, baseline logGFAP, logIL-6, and TNF-α remained associated with smaller Montreal Cognitive Assessment score changes.

In this uncontrolled cohort, cognitive rehabilitation was associated with short-term cognitive, functional, and biomarker changes. Higher baseline inflammatory biomarker levels were associated with smaller pre–post changes, with GFAP showing the strongest association. These exploratory findings do not establish efficacy or causality and require confirmation in randomized controlled studies.