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  • 1
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    Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 9 ( 2023-09-01), p. 3719-3734
    Details
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 9 ( 2023-09-01), p. 3719-3734
    Kurzfassung: Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer’s disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = −0.062, P = 0.032), higher education level (Stβinteraction = −0.072, P = 0.011) and higher intracranial volume (Stβinteraction = −0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer’s disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awad100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2023
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Determinants of cognitive and brain resilience to tau pathology: A longitudinal analysis
    Wiley ; 2023
    In:  Alzheimer's & Dementia Vol. 19, No. S3 ( 2023-06)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. S3 ( 2023-06)
    Kurzfassung: Mechanisms of resilience against tau pathology in individuals across the Alzheimer’s disease (AD) spectrum are insufficiently understood. Longitudinal data is necessary for revealing which factors contribute to maintaining cognition (cognitive resilience, CR) or preserving brain structure (brain resilience, BR) despite elevated tau, and for clarifying whether these factors provide a baseline advantage and/or moderate rates of brain structural and cognitive change. We therefore investigated whether age, sex, education, APOE‐e4 status, intracranial volume (ICV) and cortical thickness (in CR analysis) moderate the association between baseline tau load and subsequent changes in cognition and cortical thickness. Methods The study included 341 amyloid‐β‐positive individuals from a multi‐cohort dataset (BioFINDER‐1/AVID/ADNI/UCSF), diagnosed with MCI or AD dementia at the time of the baseline [ 18 F]flortaucipir tau‐PET scan, who had longitudinal cognitive assessments (CR sample). A subset (n = 133) additionally underwent longitudinal structural MRI (BR sample). We used (separate) linear mixed‐effect models with MMSE as outcome to investigate the association of key baseline variables‐of‐interest (age, sex, APOE‐e4 status, education, ICV and global cortical thickness) with cognitive decline in the presence of tau (covaried for cohort). A three‐way interaction between time, tau and the predictor‐of‐interest was initially assessed. In the absence of a moderation effect, we subsequently assessed models including only the two‐way interaction between each predictor and time. These analyses were repeated with global cortical thinning as an outcome variable. Results Characteristics of the CR sample and BR sub‐sample are described in Table‐1. Models revealed that younger age (β Interaction = ‐0.18, p 〈 0.01), higher education (β Interaction = ‐0.62, p 〈 0.001), larger ICV (β Interaction = ‐8.12, p 〈 0.01) and greater cortical thickness (β Interaction = ‐9.9, p 〈 0.05) were related to higher CR, as these factors moderated the relationship between tau pathology and decline in MMSE (Figure‐1,2). No predictor moderated tau effects on cortical thinning nor explained additional variance (Table‐2). Conclusion This study indicates that tau pathology affects cognitive decline differently across age, education, ICV and cortical thickness levels. Understanding moderators of prospective cognitive decline and cortical thinning related to tau pathology, as well as their complex interactions, may be relevant for improving prognosis and clinical trial design in AD.
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v19.S3
    DOI: 10.1002/alz.061631
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2201940-6
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  • 3
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    Differential effects of cognitive reserve and brain reserve on cognition in Alzheimer disease
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Neurology Vol. 90, No. 2 ( 2018-01-09), p. e149-e156
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 90, No. 2 ( 2018-01-09), p. e149-e156
    Kurzfassung: To examine cross-sectional effects of cognitive reserve (CR) and brain reserve (BR) on cognition across the spectrum of Alzheimer disease (AD). Methods We included 663 AD biomarker–positive participants with dementia (probable AD, n = 462) or in the predementia stages (preclinical/prodromal AD, n = 201). Education was used as a proxy of CR and intracranial volume as a proxy of BR. Cognition was assessed across 5 domains (memory, attention, language, visuospatial, and executive functions). We performed multiple linear regression models to examine effects of CR and BR on cognitive domain Z scores, adjusted for cerebral atrophy. Furthermore, we assessed differences in effects according to disease stage and across degrees of total reserve using a 4-level variable (high CR/high BR, high CR/low BR, low CR/high BR, and low CR/low BR). Results We found positive, independent effects of both CR and BR across multiple cognitive domains. Stratification for disease stage showed that effects of CR on attention and executive functioning were greater in predementia than in dementia (β = 0.39 vs β = 0.21 [Welch t = 2.40, p 〈 0.01] and β = 0.46 vs β = 0.26 [ t = 2.83, p 〈 0.01]). Furthermore, we found a linear trend for better cognitive performance in all domains in the high CR/high BR group, followed by high CR/low BR, low CR/high BR, and then low CR/low BR ( p for trend 〈 0.05). Conclusions CR and BR both independently mitigate cognitive symptoms in AD. The positive effect of CR is most strongly expressed in the predementia stages and the additive effects of high CR and BR are most beneficial.
    Materialart: Online-Ressource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000004802
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2018
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    A neuroimaging approach to capture cognitive reserve: Application to Alzheimer's disease : Capturing Cognitive Reserve
    Wiley ; 2017
    In:  Human Brain Mapping Vol. 38, No. 9 ( 2017-09), p. 4703-4715
    Details
    In: Human Brain Mapping, Wiley, Vol. 38, No. 9 ( 2017-09), p. 4703-4715
    Materialart: Online-Ressource
    ISSN: 1065-9471
    URL: Issue
    URL: Article
    DOI: 10.1002/hbm.v38.9
    DOI: 10.1002/hbm.23695
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2017
    ZDB Id: 1492703-2
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  • 5
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    P2‐605: AN OCCUPATIONAL HISTORY IN THE TRANSPORTATION AND LOGISTICS SECTOR IS RELATIVELY COMMON AMONG INDIVIDUALS WITH VASCULAR DEMENTIA
    Wiley ; 2019
    In:  Alzheimer's & Dementia Vol. 15, No. 7S_Part_16 ( 2019-07)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 15, No. 7S_Part_16 ( 2019-07)
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Article
    DOI: 10.1016/j.jalz.2019.06.3015
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2019
    ZDB Id: 2201940-6
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  • 6
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    O4‐05‐03: A LONGITUDINAL STUDY OF THE EFFECTS OF EDUCATION AND INTRACRANIAL VOLUME ON COGNITIVE CHANGES AND MORTALITY RATES IN ALZHEIMER'S DISEASE
    Wiley ; 2019
    In:  Alzheimer's & Dementia Vol. 15, No. 7S_Part_24 ( 2019-07)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 15, No. 7S_Part_24 ( 2019-07)
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Article
    DOI: 10.1016/j.jalz.2019.06.4766
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2019
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Measuring Resilience and Resistance in Aging and Alzheimer Disease Using Residual Methods : A Systematic Review and Meta-analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 97, No. 10 ( 2021-09-7), p. 474-488
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 10 ( 2021-09-7), p. 474-488
    Kurzfassung: There is a lack of consensus on how to optimally define and measure resistance and resilience in brain and cognitive aging. Residual methods use residuals from regression analysis to quantify the capacity to avoid (resistance) or cope (resilience) “better or worse than expected” given a certain level of risk or cerebral damage. We reviewed the rapidly growing literature on residual methods in the context of aging and Alzheimer disease (AD) and performed meta-analyses to investigate associations of residual method–based resilience and resistance measures with longitudinal cognitive and clinical outcomes. Methods A systematic literature search of PubMed and Web of Science databases (consulted until March 2020) and subsequent screening led to 54 studies fulfilling eligibility criteria, including 10 studies suitable for the meta-analyses. Results We identified articles using residual methods aimed at quantifying resistance (n = 33), cognitive resilience (n = 23), and brain resilience (n = 2). Critical examination of the literature revealed that there is considerable methodologic variability in how the residual measures were derived and validated. Despite methodologic differences across studies, meta-analytic assessments showed significant associations of levels of resistance (hazard ratio [HR] [95% confidence interval (CI)] 1.12 [1.07–1.17]; p 〈 0.0001) and levels of resilience (HR [95% CI] 0.46 [0.32–0.68] ; p 〈 0.001) with risk of progression to dementia/AD. Resilience was also associated with rate of cognitive decline (β [95% CI] 0.05 [0.01–0.08] ; p 〈 0.01). Discussion This review and meta-analysis supports the usefulness of residual methods as appropriate measures of resilience and resistance, as they capture clinically meaningful information in aging and AD. More rigorous methodologic standardization is needed to increase comparability across studies and, ultimately, application in clinical practice.
    Materialart: Online-Ressource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000012499
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2021
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  • 8
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    Online-Ressource
    Association of Education and Intracranial Volume With Cognitive Trajectories and Mortality Rates Across the Alzheimer Disease Continuum
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology Vol. 98, No. 16 ( 2022-04-19), p. e1679-e1691
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 16 ( 2022-04-19), p. e1679-e1691
    Kurzfassung: To investigate relationships of education and intracranial volume (ICV) (factors related to cognitive and brain reserve, respectively) with cognitive trajectories and mortality in individuals with biomarker-defined Alzheimer disease (AD). Methods We selected 1,298 β-amyloid–positive memory clinic patients with subjective cognitive decline (SCD, n = 142), mild cognitive impairment (MCI, n = 274), or AD dementia (n = 882) from the Amsterdam Dementia Cohort. All participants underwent baseline MRI and neuropsychological assessment, and 68% received cognitive follow-up (median 2.3 years, interquartile range 2.4). Mortality data were collected from the Central Public Administration. In the total sample and stratified by disease stage (i.e., SCD/MCI vs dementia), we examined education and ICV as predictors of baseline and longitudinal cognitive performance on 5 cognitive domains (memory, attention, executive, language, and visuospatial functions; linear mixed models) and time to death (Cox proportional hazard models). Analyses were adjusted for age, sex, whole brain gray matter atrophy, and MRI field strength. Results Education and ICV showed consistent positive associations with baseline cognition across disease stages. Longitudinally, we observed a relationship between higher education and faster cognitive decline among patients with dementia on global cognition, memory, executive function, and language (range β = −0.06 to −0.13; all p 〈 0.05). Furthermore, in the total sample, both higher education and larger ICV were related to lower mortality risk (hazard ratio 0.84 and 0.82, respectively; p 〈 0.05). Discussion In this β-amyloid–positive memory clinic sample, both cognitive and brain reserve were positively associated with baseline cognition, whereas only education was related to longitudinal cognition (i.e., accelerated decline among more highly educated patients with dementia). Higher education and ICV both moderately attenuated overall mortality risk in AD.
    Materialart: Online-Ressource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000200116
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2022
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  • 9
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    IC‐P‐100: A LONGITUDINAL STUDY OF THE EFFECTS OF EDUCATION AND INTRACRANIAL VOLUME ON COGNITIVE CHANGES AND MORTALITY RATES IN ALZHEIMER'S DISEASE
    Wiley ; 2019
    In:  Alzheimer's & Dementia Vol. 15, No. 7S_Part_2 ( 2019-07)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 15, No. 7S_Part_2 ( 2019-07)
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Article
    DOI: 10.1016/j.jalz.2019.06.4943
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2019
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Residual approaches to capture resilience and resistance in aging and Alzheimer’s disease: A meta‐analysis
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. S5 ( 2021-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S5 ( 2021-12)
    Kurzfassung: There is currently no consensus on how to optimally define and measure resistance and resilience in aging and Alzheimer´s disease (AD). Residuals from regression analyses can be used to quantify whether an individual´s capacity to avoid (resistance) or cope with (resilience) cerebral damage is higher or lower than expected. We aggregated the rapidly‐growing literature on neuroimaging‐based residual methods in the context of aging and AD into a meta‐analysis in order to investigate associations of residual measures of resilience and resistance with longitudinal cognitive and clinical outcomes. Method A systematic literature search of PubMed and Web‐of‐Science databases (consulted until March 2020) and subsequent screening led to 10 studies eligible for the meta‐analysis. The included studies employed a residual measure to investigate associations between either resistance or resilience and rate of cognitive decline or clinical progression (i.e., conversion to MCI or dementia). We extracted standardized regression coefficients for the former and hazard ratios (HRs) for the latter, and assessed overall effects using random‐effects models in the R(v3.6.1) metafor package(v2.4‐0). Result Resistance was most commonly measured with age‐based residuals (also known as “brain age” methods) that capture the extent to which an individual preserves brain integrity despite chronological aging. Cognitive resilience residuals quantified deviations in cognition from expected levels based on the amount of neurodegeneration [Figure 1]. There is considerable methodological variability in how the residual measures were derived and validated. Despite these methodological differences across studies (reflected in the moderate to high heterogeneity estimates), our meta‐analysis showed significant associations between resistance and risk of dementia/AD (HR[95%CI] =1.12[1.07‐ 1.17], p 〈 0.0001, I 2 =70.2%), with a lower level of resistance indicating a higher risk of progression. Cognitive resilience was significantly associated with risk of progression (HR[95%CI]=0.46[0.32‐0.68] , p 〈 0.001, I 2 =94.2%) and also with rate of cognitive decline (β[95%CI]=0.05[0.01‐0.08] , p 〈 0.01, I 2 =80.3%), suggesting an overall protective role of resilience across studies (i.e. a lower level of resilience is associated with an increased risk of dementia and a faster decline) [Figure 2] . Conclusion This meta‐analysis supports the validity of residual measures to quantify resilience and resistance, as they capture clinically meaningful information in aging and AD.
    Materialart: Online-Ressource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.S5
    DOI: 10.1002/alz.055128
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2021
    ZDB Id: 2201940-6
    Standort Signatur Einschränkungen Verfügbarkeit
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