Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study

Jessa E Burling; Zoe Katz; Ziwen Yuan; Catherine Munro; Kayden Mimmack; Grace Ma; Bernard J Hanseeuw; Kathryn V Papp; Rebecca E Amariglio; Patrizia Vannini; Dorene M Rentz; Yakeel T Quiroz; Keith A Johnson; Reisa A Sperling; Deborah Blacker; Gad A Marshall; Hyun-Sik Yang; Jennifer R Gatchel

doi:10.1016/j.jagp.2024.01.020

Study Partner Report of Apathy in Older Adults is Associated with AD Biomarkers: Findings from the Harvard Aging Brain Study

Am J Geriatr Psychiatry. 2024 Jan 28:S1064-7481(24)00020-4. doi: 10.1016/j.jagp.2024.01.020. Online ahead of print.

Authors

Jessa E Burling¹, Zoe Katz², Ziwen Yuan¹, Catherine Munro³, Kayden Mimmack¹, Grace Ma⁴, Bernard J Hanseeuw⁵, Kathryn V Papp⁶, Rebecca E Amariglio⁶, Patrizia Vannini⁶, Dorene M Rentz⁶, Yakeel T Quiroz⁷, Keith A Johnson⁸, Reisa A Sperling⁶, Deborah Blacker⁹, Gad A Marshall⁶, Hyun-Sik Yang⁶, Jennifer R Gatchel¹⁰

Affiliations

¹ Department of Neurology (JEB, ZY, KM, KVP, REA, PV, DMR, YTQ, KAJ, RAS, GAM, H-SY), Massachusetts General Hospital, Boston, MA.
² Washington University School of Medicine in St. Louis (ZK), St. Louis, MO.
³ Department of Neurology (CM, KVP, REA, PV, DMR, KAJ, RAS, GAM, H-SY), Brigham and Women's Hospital, Boston, MA; Department of Psychiatry (CM, YTQ, DB, JRG), Massachusetts General Hospital, Boston, MA; Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA.
⁴ Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA; Department of Psychiatry (GM), Brigham and Women's Hospital, Boston, MA.
⁵ Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA; Department of Radiology (BJH), Massachusetts General Research Institute, Boston, MA; Department of Neurology (BJH), Cliniques Universitaires Saint-Luc, Brussels, Belgium.
⁶ Department of Neurology (JEB, ZY, KM, KVP, REA, PV, DMR, YTQ, KAJ, RAS, GAM, H-SY), Massachusetts General Hospital, Boston, MA; Department of Neurology (CM, KVP, REA, PV, DMR, KAJ, RAS, GAM, H-SY), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA.
⁷ Department of Neurology (JEB, ZY, KM, KVP, REA, PV, DMR, YTQ, KAJ, RAS, GAM, H-SY), Massachusetts General Hospital, Boston, MA; Department of Psychiatry (CM, YTQ, DB, JRG), Massachusetts General Hospital, Boston, MA; Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA.
⁸ Department of Neurology (JEB, ZY, KM, KVP, REA, PV, DMR, YTQ, KAJ, RAS, GAM, H-SY), Massachusetts General Hospital, Boston, MA; Department of Neurology (CM, KVP, REA, PV, DMR, KAJ, RAS, GAM, H-SY), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA; Department of Radiology (KAJ), Massachusetts General Hospital, Boston, MA.
⁹ Department of Psychiatry (CM, YTQ, DB, JRG), Massachusetts General Hospital, Boston, MA; Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA; Department of Epidemiology (DB), Harvard T. H. Chan School of Public Health, Boston, MA.
¹⁰ Department of Psychiatry (CM, YTQ, DB, JRG), Massachusetts General Hospital, Boston, MA; Harvard Medical School (CM, GM, BJH, KVP, REA, PV, DMR, YTQ, KAJ, RAS, DB, GAM, H-SY, JRG), Boston, MA; Department of Psychiatry (JRG), Massachusetts General Hospital, Boston MA; Department of Psychiatry (JRG), McLean Hospital, Belmont, MA; Department of Psychiatry (JRG), Baylor College of Medicine, Houston, TX; Michael E. DeBakey VA Medical Center (JRG), Houston, TX. Electronic address: jgatchel@partners.org.

PMID: 38443298
DOI: 10.1016/j.jagp.2024.01.020

Abstract

Objectives: We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults.

Design: The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study (HABS), a longitudinal cohort study. Participants were cognitively unimpaired without clinically significant neuropsychiatric symptoms at HABS baseline. The dependent variables, apathy evaluation scale-self (AES-S) and informant (AES-I), were administered cross-sectionally between years 6-9 and compared to the independent variables, amyloid and tau PET neuroimaging, from the same year.

Setting: Community-dwelling participants assessed at research visits in an academic medical center.

Participants: Participants (n = 170) completed assessments within 1.5 years of their neuroimaging visit. At the time of apathy assessment, N = 156 were cognitively unimpaired and 14 had progressed to mild cognitive impairment (n = 8) or dementia (n = 6).

Measurements: We utilized linear regression models to assess cross-sectional associations of AES-S and AES-I with AD PET imaging measures (beta-amyloid (Pittsburgh Compound B) and tau (Flortaucipir)), covarying for age, sex, education, and the time between PET scan-apathy assessment.

Results: AES-I was significantly associated with beta-amyloid and temporal lobe tau, and the associations were retained after further adjusting for depressive symptoms. The associations between AES-S and AD biomarkers were not significant. In an exploratory subgroup analysis of cognitively unimpaired individuals with elevated Aβ, we observed an association between AES-I and inferior temporal tau.

Conclusions: Study-partner-reported, but not self-reported, apathy in older adults is associated with AD pathology, and we observed this relationship starting from the preclinical stage. Our findings highlight the importance of collateral information in capturing AD-related apathy.

Keywords: Alzheimer's disease; Apathy; amyloid; positron emission tomography; study-partner-report; tau.

Abstract

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