Evidence map›Paper›PMID 41102738›Full record

ArticleAlzheimer's research & therapy2025

Multidimensional cognitive deficits in the typical and atypical variants of Alzheimer's disease.

Shalom K Henderson, Alexander G Murley, Thomas E Cope, Lucy Bowns, Maura Malpetti, Karalyn E Patterson, James B Rowe, Matthew A Lambon Ralph

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Shalom K HendersonMedical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, CB2 7EF, UK. Shalom.Henderson@mrc-cbu.cam.ac.uk.
Alexander G MurleyDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Thomas E CopeMedical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, CB2 7EF, UK.
Lucy BownsDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Maura MalpettiDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Karalyn E PattersonMedical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, CB2 7EF, UK.
James B Rowe *Medical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, CB2 7EF, UK.
Matthew A Lambon Ralph *Medical Research Council (MRC) Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, CB2 7EF, UK.

Funding

Gates Cambridge Trust OPP1144
6 · The paper itself

Abstract

backgroundIn this two-part investigation, we examined whether Alzheimer's disease (AD) phenotypes are distinct clinical entities or represent positions within a graded multidimensional space.

methodsFirst, using a large retrospective dataset of past research participants (n = 413) from memory clinics, we examined the comparative distributions of cognitive performance in people diagnosed with typical amnestic AD (tAD), logopenic variant of primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA), across a broad range of disease severities. Secondly, a prospective deep phenotyping study of lvPPA (n = 18) compared to typical AD (n = 9) addressed the following questions: (1) Does the multidimensional cognitive pattern of impairment only emerge in advanced lvPPA, and how does it compare to tAD? (2) Do memory deficits in lvPPA appear in a simple clinic-level cognitive assessment or require in-depth neuropsychological investigation? (3) To what extent is performance on verbal episodic memory attributable to language impairment? (4) Do the patterns of decline in lvPPA and tAD stay categorical or multidimensional over time? We explored the associations between scores derived from a principal component analysis of cognitive measures, and grey matter volumes in key memory- and language-related brain regions, at baseline and longitudinally.

resultsThe clinic-level assessment revealed similar results in both the prospective and retrospective data: (i) patients showed graded distinctions (e.g., predominant visual versus language impairment in people with PCA versus lvPPA) and overlap (e.g., shared weakness in domains such as memory); and (ii) people with lvPPA and tAD were equally impaired on both verbal and non-verbal memory tests. Longitudinal assessment showed phenotypic dispersion: (i) people with tAD showed varied patterns of phenotypic differentiation; and (ii) people with lvPPA and lvPPA + exhibited a multidimensional pattern of decline with decreasing principal component scores and worsening multi-domain cognitive performance. The results of Bayesian linear regressions showed evidence for the association of grey matter volumes in language and memory networks with principal component analysis derived scores.

conclusionsThe graded distinctions amongst typical amnestic and atypical (language and visual) phenotypes of AD support the proposal for a transdiagnostic, multidimensional phenotype geometry that spans all AD subtypes.

Indexed as

Alzheimer DiseaseAphasia, Primary ProgressiveCognition DisordersCognitive DysfunctionAgedAged, 80 and overAtrophyBrainFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsPhenotypeProspective StudiesEpisodic memoryLogopenic variant of primary progressive aphasiaPosterior cortical atrophyTypical amnestic Alzheimer’s disease

Identifiers

PMID41102738
PMCPMC12532852

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.