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Cognitive and Functional Change Over Time in Cognitively Healthy Individuals According to Alzheimer Disease Biomarker-Defined Subgroups.
Dubbelman, Mark A; Hendriksen, Heleen M A; Harrison, John E; Vijverberg, Everard G B; Prins, Niels D; Kroeze, Lior A; Ottenhoff, Lois; Van Leeuwenstijn, Mardou M S S A; Verberk, Inge M W; Teunissen, Charlotte E; van de Giessen, Elsmarieke M; Van Harten, Argonde C; Van Der Flier, Wiesje M; Sikkes, Sietske A M.
Afiliación
  • Dubbelman MA; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Hendriksen HMA; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Harrison JE; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Vijverberg EGB; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Prins ND; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Kroeze LA; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Ottenhoff L; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Van Leeuwenstijn MMSSA; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Verberk IMW; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Teunissen CE; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • van de Giessen EM; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Van Harten AC; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Van Der Flier WM; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
  • Sikkes SAM; From the Alzheimer Center Amsterdam, Neurology (M.A.D., H.M.A.H., J.E.H., E.G.B.V., L.A.K., L.O., M.M.S.S.A.V.L., I.M.W.V., C.E.T., A.C.V.H., W.M.V.D.F., S.A.M.S.), and Departments of Radiology & Nuclear Medicine (E.M.v.d.G.), Epidemiology & Data Science (W.M.V.D.F.), and Neurochemistry Labo
Neurology ; 102(2): e207978, 2024 Jan 23.
Article en En | MEDLINE | ID: mdl-38165338
ABSTRACT
BACKGROUND AND

OBJECTIVES:

It is unclear to what extent cognitive outcome measures are sensitive to capture decline in Alzheimer disease (AD) prevention trials. We aimed to analyze the sensitivity to changes over time of a range of neuropsychological tests in several cognitively unimpaired, biomarker-defined patient groups.

METHODS:

Cognitively unimpaired individuals from the Amsterdam Dementia Cohort and the SCIENCe project with available AD biomarkers, obtained from CSF, PET scans, and plasma at baseline, were followed over time (4.5 ± 3.1 years, range 0.6-18.9 years). Based on common inclusion criteria for clinical trials, we defined groups (amyloid, phosphorylated tau [p-tau], APOE ε4). Linear mixed models, adjusted for age, sex, and education, were used to estimate change over time in neuropsychological tests, a functional outcome, and 2 cognitive composite measures. Standardized regression coefficients of time in years (ßtime) were reported as outcome of interest. We analyzed change over time with full follow-up, as well as with follow-up limited to 1.5 and 3 years.

RESULTS:

We included 387 individuals (aged 61.7 ± 8.6 years; 44% female) in the following (partly overlapping) biomarker groups APOE ε4 carriers (n = 212), amyloid-positive individuals (n = 109), amyloid-positive APOE ε4 carriers (n = 66), CSF p-tau-positive individuals (n = 127), plasma p-tau-positive individuals (n = 71), and amyloid and CSF p-tau-positive individuals (n = 50), or in a control group (normal biomarkers; n = 65). An executive functioning task showed most decline in all biomarker groups (ßtime range -0.30 to -0.71), followed by delayed word list recognition (ßtime range -0.18 to -0.50). Functional decline (ßtime range -0.17 to -0.63) was observed in all, except the CSF and plasma tau-positive groups. Both composites showed comparable amounts of change (ßtime range -0.12 to -0.62) in all groups, except plasma p-tau-positive individuals. When limiting original follow-up duration, many effects disappeared or even flipped direction.

DISCUSSION:

In conclusion, functional, composite, and neuropsychological outcome measures across all cognitive domains detect changes over time in various biomarker-defined groups, with changes being most evident among individuals with more AD pathology. AD prevention trials should use sufficiently long follow-up duration and/or more sensitive outcome measures to optimally capture subtle cognitive changes over time.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Neurology Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Neurology Año: 2024 Tipo del documento: Article