Inflammatory Alterations and Multidomain Cognition in Alzheimer Disease and Related Dementias

Objective: To determine how 18kDa Translocator (TSPO) PET, which measures inflammatory alterations, is associated with domain-specific cognition in the presence and absence of elevated amyloid. Methods: This cross-sectional study uses data collected on 46 adults aged 50 and over who underwent TSPO PET (11C-ER176 SUVR) and amyloid PET (18F-Florbetaben SUVR) as well as medical, neurological, and neuropsychological assessments. Controls (n=21) were amyloid-negative and cognitively unimpaired while individuals with Alzheimer disease or related dementias (ADRD; n=25) were cognitively impaired, regardless of amyloid positivity. Cognition was assessed using the Mini-Mental State Examination (MMSE) and domain-specific tests included in the NACC UDSv3. Results: Greater TSPO is associated with lower performance in episodic memory, attention/processing speed, executive function, language, and visuospatial ability in amyloid-positive individuals, but restricted to episodic memory in amyloid-negative individuals. Conclusion: Targeting microglia as an additional or alternative strategy for cognitive impairment in Alzheimer disease and related dementias may provide further benefits, even in amyloid-negative individuals.