Cited by 623Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

The DOI matches its Crossref record, with a small difference in title or year; 137 of the 143 references it cites were found in a registry or an index; 3 of the 159 sources its claims cite were checked for support.

The Alzheimer’s Disease Clinical Spectrum

Open access
Atri, Alireza·2019·Medical Clinics of North America

Abstract

Alzheimer's disease (AD) care requires timely diagnosis and multidisciplinary management. Evaluation involves structured patient and caregiver history and symptom-function reviews, examination, and testing (laboratory and neuroimaging) to delineate impairment level, determine the cognitive-behavioral syndrome, and diagnose cause. Clinical biomarkers are available to aid high confidence in etiologic diagnosis. Management uses psychoeducation, shared goal setting, and patient-caregiver dyad decision making. When combined, pharmacologic and nonpharmacologic therapies mitigate symptoms and reduce clinical progression and care burden. AD biopathologic processes develop over decades before symptoms manifest; this period is increasingly targeted in research as an opportunity to best delay or prevent AD dementia.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes the clinical spectrum, diagnostic evaluation, and multifactorial management of Alzheimer’s disease (AD) and AD-related dementias. It emphasizes structured history, multidomain assessment, tiered testing, and modest but meaningful benefits from FDA-approved cholinesterase inhibitors and memantine alongside nonpharmacologic care.

Key findings

  • AD is the most common cause of cognitive impairment/dementia in people older than 65 years; dementia prevalence approximately doubles every 5 years from age 65 to 85, rising from about 1%–2% at 65 years to more than 30%–50% by 85 years. Among Americans older than 60 years, 16% have MCI, equating to 11.6 million individuals.
  • Amnestic MCI is greater than 90% associated with underlying AD pathology; MCI increases annual progression to dementia (relative risk 6–8), and MCI with positive AD pathology biomarkers versus negative biomarkers has a 2–3 relative risk of progression (8% vs 17%–22% per year).
  • Diagnosis remains clinical, using a 3-step formulation: identify level of impairment, define the cognitive-behavioral syndrome, and establish likely cause(s) with multitiered laboratory and neuroimaging tests. CSF and amyloid PET biomarkers are clinically available but not indicated in most symptomatic individuals; they are reserved for atypical, rapidly progressive, early-onset, or inconclusive cases.
  • Management is multifactorial: nonpharmacologic/behavioral approaches are first-line for neuropsychiatric symptoms; FDA-approved anti-AD drugs (donepezil, galantamine, rivastigmine, memantine) provide modest benefits. During initial 6–12 months, cognition/ADL/behavior/global change may improve in 10%–30%, plateau in 30%–50%, or continue to deteriorate in 20%–40%; discontinuation of cholinesterase inhibitors is on aggregate harmful.

Methods

  • Review article synthesizing clinical criteria, guidelines, and evidence for AD diagnosis and management; no primary study sample or new data collection is reported.
  • Draws on major criteria (2011 NIA-AA, International Working Group, DSM-5, 2018 NIA-AA research framework), randomized controlled trials, meta-analyses, open-label extensions, and prospective observational cohort studies.
  • Main analysis is narrative synthesis with clinical recommendations, including tables for risk factors, history/symptom-function review, tiered testing, differential diagnosis, and FDA-approved medication dosing.

Limitations

  • The paper does not include a stated limitations section.
  • Evident from the text: it is a narrative clinical review without a described systematic search strategy or formal evidence-quality appraisal; recommendations rely on cited guidelines, trials, meta-analyses, and observational cohort studies.
  • Evident from the text: the author discloses honoraria for consulting, educational lectures/programs/materials, or advisory boards from multiple pharmaceutical companies and institutional investigational study/trial funding.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.mcna.2018.10.009

Cites

137 of 137 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

64 Not checked yet · 10 Own interpretation · 2 Partly supported · 2 No basis given · 1 Supported so far · accuracy not yet measured

Verify all 156 references — free account

Show all 39 claims

  • It may state two separate claims as one. 29
  • Probably not a substantial claim. 18
40 of 40
  • The paper relies on this without support.

    AD clinical syndromes, Cognitive-Behavioral Syndromes (CBS) presumed to be due to AD, are heterogeneous, particularly in younger individuals (65 years of age or younger).

    “AD clinical (ADc) syndromes, Cognitive-Behavioral Syndromes (CBS) presumed to be due to AD, are heterogeneous, particularly in younger individuals (65 years of age or younger).”
  • The paper relies on this without support.

    Amnestic-MCI is greater than 90% associated with underlying AD pathology.

    “Amnestic-MCI is greater than 90% associated with underlying AD pathology.”
  • The paper relies on this without support.

    MCI significantly increases risk of annual progression to dementia (relative risk 6-8).

    “MCI significantly increases risk of annual progression to dementia (relative risk [RR] 6-8).”
  • The paper relies on this without support.

    Pathologic tangle findings correlate best with symptoms.

    “Pathologic tangle findings correlate best with symptoms.”
  • The paper relies on this without support.

    The MoCA is a good initial choice for detection; it takes approximately 8 to 12 minutes to administer, has good psychometric properties, acceptable sensitivity to detection of mild impairment, and is available in several forms and languages.

    “The MoCA is a good initial choice for detection; it takes approximately 8 to 12 minutes to administer, has good psychometric properties, acceptable sensitivity to detection of mild impairment, and is available in several forms and languages.”
  • The paper relies on this without support.

    Creutzfeldt-Jakob disease is on the differential diagnosis of atypical Alzheimer disease clinical spectrum syndromes when there is rapid onset and progression of symptoms over weeks to months.

    “Prion diseases are very rare but Creutzfeldt-Jakob disease is on the DDx of atypical ADc syndromes when there is rapid onset and progression of symptoms (over weeks to months).”
  • The paper relies on this without support.

    Overall poor and problem behaviors by the demented individual are not intentional but are due to disease, brain injury or damage, and diminished capacities.

    “It is important for caregivers to appreciate that overall poor and problem behaviors by the demented individual are not intentional (eg, to be mean, ornery, or vindictive) but are due to disease, brain injury or damage, and diminished capacities.”
  • The paper relies on this without support.

    Without accurate diagnosis and appropriate disclosure no care can be provided.

    “because without accurate diagnosis and appropriate disclosure no care can be provided”
8 of 8

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Metadata

Authors
Atri, A.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Atri, Alireza
Venue
Medical Clinics of North America
Publisher
Elsevier BV
Published
2019-03
Volume
103
Issue
2
Pages
263-293
ISSN
0025-7125 (ISSN-L)
OpenAlex
W2912556930
Cited by
623
References
143
Citations by year
2026: 61 · 2025: 111 · 2024: 131 · 2023: 122 · 2022: 90 · 2021: 65 · 2020: 34 · 2019: 7
FWCI
8.28
Type
journal article
Language
en
Open access
Locations
  • Medical Clinics of North America (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Novartis
  • The American College of Radiology
  • AbbVie
  • Avid
  • Biogen
  • Lilly
  • Lundbeck
  • Merck
  • vTV
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 › Oncology › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, clinical spectrum, dementia diagnosis, clinical biomarkers, patient-caregiver dyads, shared decision-making, psychoeducation, pharmacotherapy, non-pharmacological treatment, disease progression, preclinical Alzheimer's disease, dementia prevention
MeSH terms
Alzheimer Disease, Diagnosis, Differential, Humans, Parkinson Disease, Biomarkers, Disease Progression, Neuroimaging

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