Beyond memory impairment: the complex phenotypic landscape of Alzheimer's disease

Stathis Argyriou; John F Fullard; Josh M Krivinko; Donghoon Lee; Thomas S Wingo; Aliza P Wingo; Robert A Sweet; Panos Roussos

doi:10.1016/j.molmed.2024.04.016

Beyond memory impairment: the complex phenotypic landscape of Alzheimer's disease

Trends Mol Med. 2024 Aug;30(8):713-722. doi: 10.1016/j.molmed.2024.04.016. Epub 2024 May 30.

Authors

Stathis Argyriou¹, John F Fullard¹, Josh M Krivinko², Donghoon Lee¹, Thomas S Wingo³, Aliza P Wingo⁴, Robert A Sweet⁵, Panos Roussos⁶

Affiliations

¹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
³ Goizueta Alzheimer's Disease Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Department of Psychiatry, Emory University School of Medicine, Atlanta, GA, USA; Veterans Affairs Atlanta Health Care System, Decatur, GA, USA.
⁵ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Street, Bronx, NY, USA; Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Street, Bronx, NY, USA. Electronic address: [email protected].

PMID: 38821772
PMCID: PMC11329360 (available on 2025-08-01)
DOI: 10.1016/j.molmed.2024.04.016

Abstract

Neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD) constitute multifaceted behavioral manifestations that reflect processes of emotional regulation, thinking, and social behavior. They are as prevalent in AD as cognitive impairment and develop independently during the progression of neurodegeneration. As studying NPSs in AD is clinically challenging, most AD research to date has focused on cognitive decline. In this opinion article we summarize emerging literature on the prevalence, time course, and the underlying genetic, molecular, and pathological mechanisms related to NPSs in AD. Overall, we propose that NPSs constitute a cluster of core symptoms in AD, and understanding their neurobiology can lead to a more holistic approach to AD research, paving the way for more accurate diagnostic tests and personalized treatments embracing the goals of precision medicine.

Keywords: Alzheimer’s disease; multiomics; neuroimaging; neuropsychiatric symptoms; precision medicine.

Publication types

Review

MeSH terms

Alzheimer Disease* / genetics
Alzheimer Disease* / pathology
Animals
Cognitive Dysfunction / etiology
Humans
Memory Disorders / etiology
Phenotype*

Abstract

Publication types

MeSH terms

Grants and funding