Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression

Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative, German Dementia Competence Network, University of San Francisco Memory and Aging Center

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Alzheimer's disease (AD) is a heterogeneous disorder. Objective: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. Methods: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. Results: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; p interaction <0.001; CDR sob 1.3±0.1; p interaction <0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05). Conclusions: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.

Original languageEnglish
Pages (from-to)1029-1039
Number of pages11
JournalJournal of Alzheimer's Disease
Volume65
Issue number3
DOIs
Publication statusPublished - 1 Jan 2018

Cite this

Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative, & German Dementia Competence Network, University of San Francisco Memory and Aging Center (2018). Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression. Journal of Alzheimer's Disease, 65(3), 1029-1039. https://doi.org/10.3233/JAD-171088
Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative ; German Dementia Competence Network, University of San Francisco Memory and Aging Center. / Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression. In: Journal of Alzheimer's Disease. 2018 ; Vol. 65, No. 3. pp. 1029-1039.
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abstract = "Background: Alzheimer's disease (AD) is a heterogeneous disorder. Objective: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. Methods: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. Results: Patients were 71±9 years old; 541 (51{\%}) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; p interaction <0.001; CDR sob 1.3±0.1; p interaction <0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05). Conclusions: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.",
keywords = "Alzheimer's disease, clustering, cognition, dementia, disease progression, mortality, phenotypes, subtypes",
author = "{Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative} and {German Dementia Competence Network, University of San Francisco Memory and Aging Center} and Scheltens, {Nienke M.E.} and Tijms, {Betty M.} and Heymans, {Martijn W.} and Rabinovici, {Gil D.} and Cohn-Sheehy, {Brendan I.} and Miller, {Bruce L.} and Kramer, {Joel H.} and Steffen Wolfsgruber and Michael Wagner and Johannes Kornhuber and Oliver Peters and Philip Scheltens and {Van Der Flier}, {Wiesje M.}",
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Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative & German Dementia Competence Network, University of San Francisco Memory and Aging Center 2018, 'Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression' Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1029-1039. https://doi.org/10.3233/JAD-171088

Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression. / Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative; German Dementia Competence Network, University of San Francisco Memory and Aging Center.

In: Journal of Alzheimer's Disease, Vol. 65, No. 3, 01.01.2018, p. 1029-1039.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression

AU - Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative

AU - German Dementia Competence Network, University of San Francisco Memory and Aging Center

AU - Scheltens, Nienke M.E.

AU - Tijms, Betty M.

AU - Heymans, Martijn W.

AU - Rabinovici, Gil D.

AU - Cohn-Sheehy, Brendan I.

AU - Miller, Bruce L.

AU - Kramer, Joel H.

AU - Wolfsgruber, Steffen

AU - Wagner, Michael

AU - Kornhuber, Johannes

AU - Peters, Oliver

AU - Scheltens, Philip

AU - Van Der Flier, Wiesje M.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Alzheimer's disease (AD) is a heterogeneous disorder. Objective: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. Methods: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. Results: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; p interaction <0.001; CDR sob 1.3±0.1; p interaction <0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05). Conclusions: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.

AB - Background: Alzheimer's disease (AD) is a heterogeneous disorder. Objective: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. Methods: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. Results: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; p interaction <0.001; CDR sob 1.3±0.1; p interaction <0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05). Conclusions: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.

KW - Alzheimer's disease

KW - clustering

KW - cognition

KW - dementia

KW - disease progression

KW - mortality

KW - phenotypes

KW - subtypes

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U2 - 10.3233/JAD-171088

DO - 10.3233/JAD-171088

M3 - Article

VL - 65

SP - 1029

EP - 1039

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

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Amsterdam Dementia Cohort, Alzheimer's Disease Neuroimaging Initiative, German Dementia Competence Network, University of San Francisco Memory and Aging Center. Prominent non-memory deficits in Alzheimer's disease are associated with faster disease progression. Journal of Alzheimer's Disease. 2018 Jan 1;65(3):1029-1039. https://doi.org/10.3233/JAD-171088