Neural Correlates of Daily Function: A Pilot Study of the White Matter Retrogenesis Hypothesis and Three Separate Performance-Based Functional Assessments

• Type of Material: Article
• Authors: Luis D Medina, University of Houston; Kate Heffernan, Emory University; Samantha Holden, University of Colorado, School of Medicine; Abigail Simpson, University of Colorado, School of Medicine; Brianne M Bettcher, University of Colorado, School of Medicine
• Language: English
• Date: 2022-01-01
• Publisher: American Psychological Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 American Psychological Association
• Final Published Version (URL): http://dx.doi.org/10.1037/neu0000649
• Title of Journal or Parent Work: NEUROPSYCHOLOGY
• Volume: 35
• Issue: 1
• Start Page: 103
• End Page: 110
• Grant/Funding Information: Support for this research was provided by an Alzheimer’s Association Research Fellowship (AARFD-16-440752) and NIH/NCRR Colorado CTSI Grant Numbers UL1 RR025780 and UL1 TR002535, and NIH High-End Instrumentation Grant S10OD018435. Aspects of this research were supported by philanthropic funds raised for the University of Colorado Alzheimer’s and Cognition Center (CUACC). Its contents are the authors’ sole responsibility and do not necessarily represent official NIH views.
• Keywords: cognition; Alzheimer’s disease; activities of daily living; aging; mild cognitive impairment

Abstract

Objective: Increasing evidence points to mild alterations in everyday functioning early in the course of Alzheimer’s disease and related dementias (ADRD), despite prior research suggesting functional declines occur primarily in later stages. However, daily function assessment is typically accomplished with subjective self- or informant-report, which can be prone to error due to various factors. Performance-based functional assessments (PBFAs) allow for objective evaluation of daily function abilities, but little is known on their sensitivity to the earliest ADRD-related brain alterations. We aimed to determine the neural correlates of three different PBFAs in a pilot study. Method: A total of 40 older participants (age=70.9±6.5 years; education=17.0±2.6 years; 51.5% female; 10.0% non-White; 67.5% cognitively normal) completed standardized PBFAs related to medication management (MM), finances (FIN), and communication abilities (COM). Participants underwent diffusion tensor imaging (DTI) scans, from which mean fractional anisotropy (FA) composite scores of late- (LMF) and early-myelinated (EMF) fibers were calculated. Linear regression analyses controlling for age and global cognition were used to assess the relationship of PBFAs with FA. Results: Better performance on MM was associated with higher mean FA on LMF composite (t38=2.231, p=0.032), while FIN and COM were not (ps>0.05). PBFAs were not associated with EMF (p>0.05). Conclusions: Our preliminary findings demonstrate better performance on a PBFA of medication management is associated with higher FA in late-myelinated white matter tracts. Despite a small sample size, these results are consistent with growing evidence that performance-based functional assessments may be a useful tool in identifying early changes related to ADRD.