Regional Tau Correlates of Instrumental Activities of Daily Living and Apathy in Mild Cognitive Impairment and Alzheimer’s Disease Dementia

Abstract

Background: Instrumental activities of daily living (IADL) impairment and apathy occur in early-stage Alzheimer’s disease (AD) and are associated with regional atrophy and hypometabolism in vivo and greater tau burden at autopsy. Objective: To explore the association between IADL impairment, apathy, and in vivo regional tau in mild cognitive impairment (MCI) and AD dementia. Methods: Forty participants (24 MCI, 16 AD dementia) underwent assessments of IADL (Functional Activities Questionnaire, FAQ) and apathy (Apathy Evaluation Scale Informant report, AES-I). Regional tau was assessed using flortaucipir positron emission tomography (PET) and amyloid using Pittsburgh Compound B PET. Regions with unadjusted associations of p≤0.01 were entered into regression models assessing the relationship between tau and FAQ or AES-I, adjusting for age, sex, and cognition, with/without a tau by amyloid interaction. Results: Unadjusted IADL impairment but not apathy was associated with greater tau in multiple regions. After adjusting for covariates, for medial orbitofrontal and entorhinal cortex the interaction between tau and amyloid was associated with IADL impairment and for anterior cingulate it was not but independent associations with both tau and amyloid were retained. With whole brain analyses, similar results were seen for IADL, while for apathy tau in small clusters within the right anterior cingulate and dorsolateral prefrontal cortices were seen, which were more pronounced in individuals with greater amyloid. Conclusions: This exploratory study suggests that IADL impairment in AD is associated with medial temporal and frontal tau, especially in individuals with elevated amyloid, while apathy may be associated with right frontal tau.

Relationship between Performance on the Mini-Mental State Examination Sub-Items and Activities of Daily Living in Patients with Alzheimer’s Disease

“…From these facts, "writing" may be associated with spontaneity. In addition, previous studies have also reported that spontaneity is strongly associated with IADL [35,36]. Therefore, since "writing" has a feature that requires spontaneity and multiple cognitive functions such as executive function and visual-spatial cognitive function, it may have suggested a strong association with IADL.…”

Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease

“…Disturbances in drive and emotions in AD are often referred to as manifestations of frontal lobe pathology, wherefore an association with temporal tau deposition could be considered a somewhat unexpected finding in its relation to neuropsychiatric symptoms. Yet, most pathological studies displaying such frontal associations have been conducted on MCI and AD dementia samples, not on CU samples 27 , 28 . Some studies focusing on cerebral atrophy have instead strengthened the role of the temporal lobe pathology in neuropsychiatric and behavioral symptoms, such as apathy, among CU subjects 29 , 30 .…”

Neuroanatomical Abnormalities in Older Depressed Adults With Apathy: A Systematic Review

“…For example, apathy is more common in those with neurofibrillary tangles in the left ACC than it is in those with predominant Alzheimer disease pathology in other areas. 43,80 In addition, in vivo analysis demonstrates an association between apathy severity and tau deposition in the ACC and DLPFC, 81 as well as amyloid-b deposition throughout the bilateral frontal cortex and right ACC. 63 Parkinson Disease.…”