Glucose hypometabolism is associated with brain pathology and cognitive‐behavioral symptoms in autosomal dominant Alzheimer’s disease: Findings from the Colombia‐Boston (COLBOS) Biomarker Study
Authors: Langella Stephanie , Kaplan Elizabeth , Baena Ana Y. , Londono Natalia , Munera Diana , Vila‐Castelar Clara , Alvarez Sergio , Vidal Monica , Properzi Michael J , Sanchez Justin S , Sperling Reisa A. , Johnson Keith A. , Lopera Francisco , Hanseeuw Bernard J , Quiroz Yakeel T. 
Published: December 2023

Background

Hypometabolism is observed in early Alzheimer’s disease (AD), though its relation to underlying pathology remains uncertain. We first examined the relationships between glucose metabolism, β‐amyloid (Aβ), and tau in Presenilin‐1 (PSEN1) E280A mutation carriers and non‐carriers from the Massachusetts General Hospital Colombia‐Boston (COLBOS) Biomarker Study. We then examined the associations between glucose metabolism and episodic memory and depressive symptoms, two cognitive‐behavioral domains affected in early AD.

Method

Fludeoxyglucose (18F‐fludeoxyglucose;FDG) positron emission tomography (PET) images and neuropsychological assessments were analyzed from 31 PSEN1 E280A carriers (20F; mean age = 39 years; 21 cognitively unimpaired/10 cognitively impaired) and 33 age‐matched non‐carrier family members (20F, mean age = 39 years). Measures of Aβ (11C‐Pittsburgh compound‐B) and tau (18F‐flortaucipir) PET were available in a subset of this sample (22 carriers, 26 non‐carriers), collected on average 1.36 years prior to FDG‐PET. Entorhinal cortex, inferior temporal cortex, and precuneus were FDG‐ and tau‐PET regions of interest (ROIs). Group differences in FDG were tested followed by post‐hoc pairwise comparisons (non‐carriers/unimpaired carriers/impaired carriers). Linear regression was used to assess (1) age‐related trajectories of FDG as function of group (carrier/non‐carrier); and (2) whether cortical Aβ and regional tau predict FDG in carriers. FDG associations with memory (CERAD Word List Delayed Recall) and depression (Geriatric Depression Scale) were tested using Spearman correlation within carriers.

Result

Impaired carriers had lower metabolism in all ROIs compared to unimpaired carriers (ps<.006) and non‐carriers (ps<.031); unimpaired carriers and non‐carriers did not differ (ps>.116). Age was more negatively associated with precuneus (p = .030) and inferior temporal (p = .006) metabolism in carriers than non‐carriers. Age‐related trajectories of entorhinal metabolism did not differ by group (p = .107). In carriers, higher cortical Aβ and regional tau were associated with lower metabolism in all ROIs (ps<.013); only the relationship between precuneus tau and FDG survived adjustment for age (p = .05). Higher recall was associated with lower metabolism in all ROIs (ps<.017). Higher depressive symptoms were associated with lower inferior temporal metabolism (p = .014).

Conclusion

Glucose hypometabolism is evident in prodromal autosomal dominant AD and may reflect both Aβ and tau pathology. Hypometabolism is associated with increased cognitive‐behavioral symptoms. Future studies should consider longitudinal associations between these measures.