Neurovascular coupling dysfunction associated with cognition and glial fibrillary acidic protein along the Alzheimer's disease continuum

BackgroundEarly neurovascular coupling (NVC) dysfunction in Alzheimer's disease (AD) remains poorly understood despite being a key pathological feature.ObjectiveThis study aimed to investigate NVC alterations across the AD continuum, including individuals with AD, mild cognitive impairment (MCI), and cognitively normal (CN) individuals, and to examine their associations with cognitive performance and plasma biomarkers.MethodsThis study included 23 CN participants, 80 MCI, and 33 AD patients. Neuronal activity was assessed using amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), which were derived from blood oxygen level-dependent functional magnetic resonance imaging signals, whereas cerebral blood flow (CBF) maps measured perfusion. Neurovascular coupling was quantified via the ALFF-CBF and ReHo-CBF. Group differences were evaluated using analysis of variance, and associations with cognitive scores and plasma biomarkers were analyzed.ResultsThe AD group exhibited lower ALFF-CBF coupling values in the left anterior cingulate and middle cingulate gyri compared with the CN and MCI groups. Reduced coupling values were positively correlated with Mini-Mental State Examination scores. In cognitively impaired groups, left anterior cingulate coupling was negatively correlated with plasma glial fibrillary acidic protein (GFAP) levels. AD patients showed decreased ReHo-CBF coupling in the left inferior frontal and middle temporal gyri.ConclusionsNeurovascular coupling dysfunction is significantly linked to cognitive impairment along the AD continuum. Reduced coupling values in key regions correlated with impaired cognition and higher plasma GFAP levels, underscoring vascular-metabolic and astroglial contributions. These findings support ALFF-CBF coupling as a promising non-invasive biomarker for early AD detection and disease monitoring.