Memory and executive function are associated with distinct patterns of regional cerebral perfusion in dementia‐free APOE‐ε4 carriers and non‐carriers. Issue 4 (1st February 2022)

• Record Type: Journal Article
• Authors: Dutt, Shubir; Yew, Belinda; Li, Yanrong; Gaubert, Aimee; Ho, Jean K; Jang, Jung Yun; Blanken, Anna E; Sible, Isabel J; Marshall, Anisa J; Kapoor, Arunima; Shao, Xingfeng; Wang, Danny JJ; Nation, Daniel A
• Is Part Of: Alzheimer's & dementia. Volume 17:Issue 4(2021)Supplement
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.056524
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The primary genetic risk factor for Alzheimer's disease is the apolipoprotein ε4 (APOE‐ε4) allele, which confers significant risk for early symptom onset and future dementia. Prior studies have examined links between memory function and medial temporal perfusion in APOE‐ε4 carriers and non‐carriers, but findings have been mixed regarding the direction of relationships. Additionally, prior work has not examined whether other cognitive domains, such as executive function, are similarly associated with functionally relevant regional perfusion (i.e., in frontal regions). The present study aimed to 1) clarify the relationship between medial temporal perfusion and memory performance and 2) examine novel links between executive function and frontal perfusion in APOE‐ε4 carriers and non‐carriers. Method: Dementia‐free older adults recruited from the community were classified as APOE‐ε4 carriers (n=18) or non‐carriers (n=30) via genotype analysis. We used pseudocontinuous arterial spin labeling MRI to quantify cerebral perfusion in regions involved in memory (medial temporal) and executive function (medial frontal). Comprehensive neuropsychological testing assessed memory (Logical Memory I & II; Visual Reproduction I & II) and executive function (Stroop color‐word interference; Trail making tests A & B, category fluency). Multiple linear regression, modeled separately within carriers and non‐carriers, examined associations between perfusion and cognition, with age, sex, and education as covariates. Result: Within APOE‐ε4 carriers, medial temporal hypoperfusion was associated with worse immediate and delayed recall memory in verbal and visual paradigms. Similarly, frontal hypoperfusion was associated with worse verbal category fluency. In non‐carriers, relationships between medial temporal perfusion and memory were absent. Relationships between frontal perfusion and executive function were in the opposite direction as those observed in APOE‐ε4 carriers, with frontal hyperperfusion predicting worse Stroop color‐word, Trails A, and Trails B performance. Conclusion: We observed positive associations between regional perfusion and corresponding cognitive domains in APOE‐ε4 carriers, while relationships were absent or negative within non‐carriers. Our findings highlight the importance of examining preclinical cerebrovascular dysfunction in relation to cognition in individuals at risk for progression to dementia. Future longitudinal studies will be needed to further examine the value of perfusion, cognition, and APOE‐ε4 carrier status in predicting future decline.