Alzheimers Dement. 2026 Aug;22(8):e71795. doi: 10.1002/alz.71795.
ABSTRACT
INTRODUCTION: Neuroinflammatory processes may play a central role in promoting mixed pathologies and cognitive impairment in the oldest-old. We hypothesize that elevated neuroinflammation, indicated by reactive astrocytosis, acts on cerebrovascular disease and separately, on amyloid beta (Aβ) pathology, to promote downstream medial temporal lobe atrophy and memory impairment.
METHODS: We examined whether plasma glial fibrillary acidic protein (GFAP) concentration is associated with vascular territory-defined white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI), global Aβ burden on positron emission tomography (PET), and episodic memory in a diverse cohort (N = 439) of the oldest-old: The LifeAfter90 Study.
RESULTS: Higher plasma GFAP was associated with increased posterior cerebral artery (PCA)-defined WMH volume, but not with global amyloid or episodic memory. Both PCA WMH and global amyloid were associated with lower regional medial temporal lobe cortical thickness, which, in turn, was associated with episodic memory.
DISCUSSION: These findings offer insights into new therapeutic and prevention strategies in the oldest-old population.
PMID:42630088 | DOI:10.1002/alz.71795