Cited by 187Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

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Heterogeneity in Alzheimer’s Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials

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Duara, Ranjan, Barker, Warren·2022·Neurotherapeutics

DOI 10.1007/s13311-022-01185-zPMC PMC9130395

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Abstract

The clinical presentation and the pathological processes underlying Alzheimer's disease (AD) can be very heterogeneous in severity, location, and composition including the amount and distribution of AB deposition and spread of neurofibrillary tangles in different brain regions resulting in atypical clinical patterns and the existence of distinct AD variants. Heterogeneity in AD may be related to demographic factors (such as age, sex, educational and socioeconomic level) and genetic factors, which influence underlying pathology, the cognitive and behavioral phenotype, rate of progression, the occurrence of neuropsychiatric features, and the presence of comorbidities (e.g., vascular disease, neuroinflammation). Heterogeneity is also manifest in the individual resilience to the development of neuropathology (brain reserve) and the ability to compensate for its cognitive and functional impact (cognitive and functional reserve). The variability in specific cognitive profiles and types of functional impairment may be associated with different progression rates, and standard measures assessing progression may not be equivalent for individual cognitive and functional profiles. Other factors, which may govern the presence, rate, and type of progression of AD, include the individuals' general medical health, the presence of specific systemic conditions, and lifestyle factors, including physical exercise, cognitive and social stimulation, amount of leisure activities, environmental stressors, such as toxins and pollution, and the effects of medications used to treat medical and behavioral conditions. These factors that affect progression are important to consider while designing a clinical trial to ensure, as far as possible, well-balanced treatment and control groups.

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See all 187

Authors: Duara, R., & Barker, W.
Affiliations: Florida International University (US)
Mount Sinai Medical Center (US)
Corresponding author: Barker, Warren
ORCID: Duara, Ranjan
Barker, Warren
Venue: Neurotherapeutics
Publisher: Elsevier BV
Published: 2022-01
Volume: 19
Issue: 1
Pages: 8-25
ISSN: 1878-7479 (ISSN-L)
DOI: 10.1007/s13311-022-01185-z
PMC: PMC9130395
OpenAlex: W4210391623
Cited by: 187
References: 215
Citations by year: 2026: 59 · 2025: 64 · 2024: 46 · 2023: 12 · 2022: 5
FWCI: 5.51
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 592 d)
Locations: Neurotherapeutics (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (1P30AG066506-01)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Keywords: Alzheimer's disease, disease heterogeneity, disease progression rate, amyloid-beta deposition, neurofibrillary tangles, atypical presentation, brain reserve, cognitive reserve, functional reserve, neuropsychiatric symptoms, comorbidities, vascular disease, neuroinflammation, genetic factors, demographic factors, lifestyle factors, clinical trial design
MeSH terms: Alzheimer Disease, Brain, Humans, Disease Progression

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Heterogeneity in Alzheimer’s Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials

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