Elevated Amyloid-β PET Scan and Cognitive and Functional Decline in Mild Cognitive Impairment and Dementia of Uncertain Etiology

Article type: Research Article

Authors: Plassman, Brenda L.^{a; b; *} | Ford, Cassie B.^c | Smith, Valerie A.^{c; d; e} | DePasquale, Nicole^d | Burke, James R.^{a; b} | Korthauer, Laura^f | Ott, Brian R.^g | Belanger, Emmanuelle^h | Shepherd-Banigan, Megan E.^{c; e; i} | Couch, Elyse^h | Jutkowitz, Eric^h | O’Brien, Emily C.^c | Sorenson, Corinna^{c; i; j} | Wetle, Terrie T.^{h; k} | Van Houtven, Courtney H.^{c; e; i}

Affiliations: [a] Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA | [b] Department of Neurology, School of Medicine, Duke University, NC, USA | [c] Department of Population Health Sciences, Duke University, Durham, NC, USA | [d] Department of Medicine, Division of General Internal Medicine, Duke University, Durham, NC, USA | [e] Durham ADAPT, Durham Veterans Affairs Medical Center, Durham, NC, USA | [f] Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA | [g] Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA | [h] Department of Health Services Policy and Practice, School of Public Health, Brown University, Providence, RI, USA. | [i] Duke-Margolis Center for Health Policy, Durham, NC, USA | [j] Sanford School of Public Policy, Duke University, Durham, NC, USA | [k] Center for Gerontology and Healthcare Research, Brown University School of Public Health, Providence, RI, USA

Correspondence: [*] Correspondence to: Brenda L. Plassman, PhD, Duke University, 2400 Pratt Street, Rm 6012, Durham, NC 27705, USA. Tel.: +1 919 668 1586; E-mail: Brenda.Plassman@duke.edu.

Abstract: Background:Elevated amyloid-β (Aβ) on positron emission tomography (PET) scan is used to aid diagnosis of Alzheimer’s disease (AD), but many prior studies have focused on patients with a typical AD phenotype such as amnestic mild cognitive impairment (MCI). Little is known about whether elevated Aβ on PET scan predicts rate of cognitive and functional decline among those with MCI or dementia that is clinically less typical of early AD, thus leading to etiologic uncertainty. Objective:We aimed to investigate whether elevated Aβ on PET scan predicts cognitive and functional decline over an 18-month period in those with MCI or dementia of uncertain etiology. Methods:In 1,028 individuals with MCI or dementia of uncertain etiology, we evaluated the association between elevated Aβ on PET scan and change on a telephone cognitive status measure administered to the participant and change in everyday function as reported by their care partner. Results:Individuals with either MCI or dementia and elevated Aβ (66.6% of the sample) showed greater cognitive decline compared to those without elevated Aβ on PET scan, whose cognition was relatively stable over 18 months. Those with either MCI or dementia and elevated Aβ were also reported to have greater functional decline compared to those without elevated Aβ, even though the latter group showed significant care partner-reported functional decline over time. Conclusions:Elevated Aβ on PET scan can be helpful in predicting rates of both cognitive and functional decline, even among cognitively impaired individuals with atypical presentations of AD.

Keywords: Activities of daily living, Alzheimer’s disease, amyloid-β , cognitive decline, dementia, functional status, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-230950

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1161-1171, 2024