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Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia. ​

Literature Information ​

DOI10.1016/j.jalz.2018.10.003
PMID30555032
JournalAlzheimer's & dementia : the journal of the Alzheimer's Association
Impact Factor11.1
JCR QuartileQ1
Publication Year2019
Times Cited186
KeywordsAlzheimer's disease, Dementia Lewy bodies, Dementia incidence, Frontotemporal dementia, Preclinical Alzheimer's disease
Literature TypeJournal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
ISSN1552-5260
Pages465-476
Issue15(3)
AuthorsRosalinde E R Slot, Sietske A M Sikkes, Johannes Berkhof, Henry Brodaty, Rachel Buckley, Enrica Cavedo, Efthimios Dardiotis, Francoise Guillo-Benarous, Harald Hampel, Nicole A Kochan, Simone Lista, Tobias Luck, Paul Maruff, José Luis Molinuevo, Johannes Kornhuber, Barry Reisberg, Steffi G Riedel-Heller, Shannon L Risacher, Susanne Roehr, Perminder S Sachdev, Nikolaos Scarmeas, Philip Scheltens, Melanie B Shulman, Andrew J Saykin, Sander C J Verfaillie, Pieter Jelle Visser, Stephanie J B Vos, Michael Wagner, Steffen Wolfsgruber, Frank Jessen, Wiesje M van der Flier

TL;DR ​

This multicenter study investigated the incidence of Alzheimer's disease and non-Alzheimer's dementia among individuals with subjective cognitive decline (SCD), finding a higher dementia incidence in memory clinic settings (17.7 per 1000 person-years) compared to community settings (14.2 per 1000 person-years). The research identified age, Mini-Mental State Examination scores, and apolipoprotein E ε4 as significant risk factors for dementia progression, highlighting the importance of monitoring SCD as a potential precursor to dementia.

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Alzheimer's disease · Dementia Lewy bodies · Dementia incidence · Frontotemporal dementia · Preclinical Alzheimer's disease

Abstract ​

INTRODUCTION In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia.

METHODS Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models.

RESULTS In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia.

DISCUSSION SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.

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Primary Questions Addressed ​

  1. What are the specific risk factors associated with subjective cognitive decline in community-based versus memory clinic settings?
  2. How does the age distribution of participants with subjective cognitive decline impact the incidence rates of Alzheimer's and non-Alzheimer's dementia?
  3. In what ways might the Mini-Mental State Examination scores correlate with the progression from subjective cognitive decline to dementia?
  4. How do the findings on subjective cognitive decline inform early intervention strategies for dementia prevention?
  5. What role does apolipoprotein E ε4 play in the differential rates of dementia incidence among individuals with subjective cognitive decline?

Key Findings ​

Research Background and Objective ​

Subjective cognitive decline (SCD) refers to the self-reported experience of cognitive decline without objective cognitive impairment. This study aims to assess the incidence rates of Alzheimer’s disease (AD) and non-AD dementia among individuals with SCD and identify risk factors influencing the progression to dementia. The research is grounded in the understanding that neurodegenerative changes may begin years before clinical symptoms appear, making early identification critical.

Main Methods/Materials/Experimental Design ​

The study included 2978 participants with SCD and 1391 controls from eleven cohorts across memory clinic and community settings. The primary outcome measure was the progression to dementia, which was analyzed using Cox proportional hazards models.

Participant Selection Flowchart:

Mermaid diagram

Statistical Analysis:

  • Incidence rates were calculated per 1000 person-years.
  • Risk factors such as age, sex, education, MMSE scores, and APOE ε4 status were evaluated.
  • Shared-frailty Cox proportional hazards models were used to account for center-specific random effects.

Key Results and Findings ​

  • Incidence Rates: The overall incidence of dementia in individuals with SCD was 17.7 per 1000 person-years (AD: 11.5, non-AD: 6.1) compared to 14.2 in controls (AD: 10.1, non-AD: 4.1).
  • Progression Rates: 6% of controls and 7% of individuals with SCD progressed to dementia during the follow-up period.
  • Risk Factors: Higher age, lower MMSE scores, and being an APOE ε4 carrier were identified as significant risk factors for dementia progression. The risk was notably higher in memory clinic settings compared to community settings.
Risk FactorHazard Ratio (95% CI)
Age1.1 (1.1–1.1)
Lower MMSE0.7 (0.66–0.8)
APOE ε4 Carrier1.8 (1.3–2.5)

Main Conclusions/Significance/Innovation ​

This study provides evidence that SCD is a precursor not only to AD but also to various forms of non-AD dementia. The significant role of recruitment setting in influencing dementia risk highlights the necessity for careful consideration in future research. The findings underscore the importance of identifying individuals with SCD who may benefit from early interventions and lifestyle modifications.

Research Limitations and Future Directions ​

  • Heterogeneity: The study faced challenges due to the heterogeneity of cohort characteristics, including differences in SCD definitions and diagnostic criteria across centers.
  • Lack of Comprehensive Data: Limited availability of cognitive tests and biomarker data may have impacted the accuracy of diagnoses.
  • Future Research: Subsequent studies should aim to include a wider range of cognitive assessments and biomarker evaluations to better differentiate between AD and non-AD dementia types. There is also a need for standardized definitions and criteria for SCD to facilitate more reliable comparisons across studies.

Overall, the study contributes valuable insights into the progression of SCD to dementia, emphasizing the need for early identification and intervention strategies.

References ​

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Literatures Citing This Work ​

  1. Computer-assisted prediction of clinical progression in the earliest stages of AD. - Hanneke F M Rhodius-Meester;Hilkka Liedes;Juha Koikkalainen;Steffen Wolfsgruber;Nina Coll-Padros;Johannes Kornhuber;Oliver Peters;Frank Jessen;Luca Kleineidam;José Luis Molinuevo;Lorena Rami;Charlotte E Teunissen;Frederik Barkhof;Sietske A M Sikkes;Linda M P Wesselman;Rosalinde E R Slot;Sander C J Verfaillie;Philip Scheltens;Betty M Tijms;Jyrki Lötjönen;Wiesje M van der Flier - Alzheimer's & dementia (Amsterdam, Netherlands) (2018)
  2. Amyloid-β Load Is Related to Worries, but Not to Severity of Cognitive Complaints in Individuals With Subjective Cognitive Decline: The SCIENCe Project. - Sander C J Verfaillie;Tessa Timmers;Rosalinde E R Slot;Chris W J van der Weijden;Linda M P Wesselman;Niels D Prins;Sietske A M Sikkes;Maqsood Yaqub;Annemiek Dols;Adriaan A Lammertsma;Philip Scheltens;Rik Ossenkoppele;Bart N M van Berckel;Wiesje M van der Flier - Frontiers in aging neuroscience (2019)
  3. Personalized risk for clinical progression in cognitively normal subjects-the ABIDE project. - Ingrid S van Maurik;Rosalinde E R Slot;Sander C J Verfaillie;Marissa D Zwan;Femke H Bouwman;Niels D Prins;Charlotte E Teunissen;Philip Scheltens;Frederik Barkhof;Mike P Wattjes;Jose Luis Molinuevo;Lorena Rami;Steffen Wolfsgruber;Oliver Peters;Frank Jessen;Johannes Berkhof;Wiesje M van der Flier; - Alzheimer's research & therapy (2019)
  4. Dietary Patterns Are Related to Clinical Characteristics in Memory Clinic Patients with Subjective Cognitive Decline: The SCIENCe Project. - Linda M P Wesselman;Astrid S Doorduijn;Francisca A de Leeuw;Sander C J Verfaillie;Mardou van Leeuwenstijn-Koopman;Rosalinde E R Slot;Maartje I Kester;Niels D Prins;Ondine van de Rest;Marian A E de van der Schueren;Philip Scheltens;Sietske A M Sikkes;Wiesje M van der Flier - Nutrients (2019)
  5. Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time. - Elizabeth Kuhn;Inès Moulinet;Audrey Perrotin;Renaud La Joie;Brigitte Landeau;Clémence Tomadesso;Alexandre Bejanin;Siya Sherif;Vincent De La Sayette;Béatrice Desgranges;Denis Vivien;Géraldine Poisnel;Gaëlle Chételat - Alzheimer's research & therapy (2019)
  6. Biomarker-Based Signature of Alzheimer's Disease in Pre-MCI Individuals. - Elena Chipi;Nicola Salvadori;Lucia Farotti;Lucilla Parnetti - Brain sciences (2019)
  7. Disability trajectories and mortality in older adults with different cognitive and physical profiles. - Giulia Grande;Davide L Vetrano;Laura Fratiglioni;Anna Marseglia;Nicola Vanacore;Erika Jonsson Laukka;Anna-Karin Welmer;Debora Rizzuto - Aging clinical and experimental research (2020)
  8. Memory Complaint Is a Surrogate for Memory Decline in the Middle-Aged: A Register-Based Study. - Yah-Yuan Wu;Wen-Chuin Hsu;Yu-Hua Huang;Wei-Min Ho;Yi-Chun Chen - Journal of clinical medicine (2019)
  9. Subjective Cognitive Decline Among Sexual and Gender Minorities: Results from a U.S. Population-Based Sample. - Monique J Brown;Robert Patterson - Journal of Alzheimer's disease : JAD (2020)
  10. The characterisation of subjective cognitive decline. - Frank Jessen;Rebecca E Amariglio;Rachel F Buckley;Wiesje M van der Flier;Ying Han;José Luis Molinuevo;Laura Rabin;Dorene M Rentz;Octavio Rodriguez-Gomez;Andrew J Saykin;Sietske A M Sikkes;Colette M Smart;Steffen Wolfsgruber;Michael Wagner - The Lancet. Neurology (2020)

... (176 more literatures)

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