Dataset Information

Associations of Brain Pathology Cognitive and Physical Markers With Age in Cognitively Normal Individuals Aged 60-102 Years.

ABSTRACT: The prevalence of brain pathologies increases with age and cognitive and physical functions worsen over the lifetime. It is unclear whether these processes show a similar increase with age. We studied the association of markers for brain pathology cognitive and physical functions with age in 288 cognitively normal individuals aged 60-102 years selected from the cross-sectional EMIF-AD PreclinAD and 90+ Study at the Amsterdam UMC. An abnormal score was consistent with a score below the 5th percentile in the 60- to 70-year-old individuals. Prevalence of abnormal scores was estimated using Generalized Estimating Equations (GEE) models. The prevalence of abnormal handgrip strength, the Digit Symbol Substitution Test, and hippocampal volume showed the fastest increase with age and abnormal MMSE score, muscle mass, and amyloid aggregation the lowest. The increase in prevalence of abnormal markers was partly dependent on sex, level of education, and amyloid aggregation. We did not find a consistent pattern in which markers of brain pathology cognitive and physical processes became abnormal with age.

SUBMITTER: Legdeur N

PROVIDER: S-EPMC7494041 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Associations of Brain Pathology Cognitive and Physical Markers With Age in Cognitively Normal Individuals Aged 60-102 Years.

Legdeur Nienke N Tijms Betty M BM Konijnenberg Elles E den Braber Anouk A Ten Kate Mara M Sudre Carole H CH Tomassen Jori J Badissi Maryam M Yaqub Maqsood M Barkhof Frederik F van Berckel Bart N BN Boomsma Dorret I DI Scheltens Philip P Holstege Henne H Maier Andrea B AB Visser Pieter Jelle PJ

The journals of gerontology. Series A, Biological sciences and medical sciences 20200901 9

The prevalence of brain pathologies increases with age and cognitive and physical functions worsen over the lifetime. It is unclear whether these processes show a similar increase with age. We studied the association of markers for brain pathology cognitive and physical functions with age in 288 cognitively normal individuals aged 60-102 years selected from the cross-sectional EMIF-AD PreclinAD and 90+ Study at the Amsterdam UMC. An abnormal score was consistent with a score below the 5th percen ...[more]

PMID: 31411322

Similar Datasets

Project description:Blood-based biomarkers could prove useful to predict Alzheimer's disease core pathologies in advance of clinical symptoms. Implementation of such biomarkers requires a solid understanding of their long-term dynamics and the contribution of confounding to their association with Alzheimer's disease pathology. Here we assess the value of plasma amyloid-β1-42/1-40, phosphorylated-tau181 and glial fibrillary acidic protein to detect early Alzheimer's disease pathology, accounting for confounding by genetic and early environmental factors. Participants were 200 monozygotic twins, aged ≥60 years with normal cognition from the european medical information framework for Alzheimer's disease study. All twins had amyloid-β status and plasma samples available at study enrolment. For 80 twins, additional plasma samples were available that had been collected approximately 10 years prior to amyloid-β status assessment. Single-molecule array assays were applied to measure amyloid-β1-42/1-40, phosphorylated-tau181 and glial fibrillary acidic protein. Predictive value of and longitudinal change in these biomarkers were assessed using receiver operating characteristic curve analysis and linear mixed models. Amyloid pathology could be predicted using blood-based biomarkers obtained at the time of amyloid status assessment (amyloid-β1-42/1-40: area under the curve = 0.65, P = 0.01; phosphorylated-tau181: area under the curve = 0.84, P < 0.001; glial fibrillary acidic protein: area under the curve = 0.74, P < 0.001), as well as using those obtained 10 years prior to amyloid status assessment (amyloid-β1-42/1-40: area under the curve = 0.69, P = 0.03; phosphorylated-tau181: area under the curve = 0.92, P < 0.001; glial fibrillary acidic protein: area under the curve = 0.84, P < 0.001). Longitudinally, amyloid-β1-42/1-40 levels decreased [β (SE) = -0.12 (0.01), P < 0.001] and phosphorylated-tau181 levels increased [β (SE) = 0.02 (0.01), P = 0.004]. Amyloid-β-positive individuals showed a steeper increase in phosphorylated-tau181 compared with amyloid-β-negative individuals [β (SE) = 0.06 (0.02), P = 0.004]. Also amyloid-β-positive individuals tended to show a steeper increase in glial fibrillary acidic protein [β (SE) = 0.04 (0.02), P = 0.07]. Within monozygotic twin pairs, those with higher plasma phosphorylated-tau181 and lower amyloid-β1-42/1-40 levels were more likely to be amyloid-β positive [β (SE) = 0.95 (0.26), P < 0.001; β (SE) = -0.28 (0.14), P < 0.05] indicating minimal contribution of confounding by genetic and early environmental factors. Our data support the use of amyloid-β1-42/1-40, phosphorylated-tau181 and glial fibrillary acidic protein as screening tools for Alzheimer's disease pathology in the normal aging population, which is of importance for enrolment of high-risk subjects in secondary, or even primary, prevention trials. Furthermore, these markers show potential as low-invasive monitoring tool of disease progression and possibly treatment effects in clinical trials.

Project description:BackgroundTo systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment.MethodsIn this longitudinal study, we included 396 cognitively normal to dementia subjects with 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive(+)/negative(-) at pre-established cut-offs, classifying subjects as Braak0/BraakI+/BraakI-IV+/BraakI-VI+/Braakatypical+. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia.ResultsBaseline global tau-PET SUVRs explained more variance (partial R2) in future cognitive decline than Centiloid across all cognitive tests (Cohen's d ~ 2, all tests p < 0.001) and diagnostic groups. Associations between tau-PET and cognitive decline remained consistent when controlling for Centiloid, while associations between amyloid-PET and cognitive decline were non-significant when controlling for tau-PET. More advanced Braak-stage was associated with gradually worsening future cognitive decline, independent of Centiloid or diagnostic group (p < 0.001), and elevated conversion risk to MCI/dementia.ConclusionTau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings.

Dataset Information

Associations of Brain Pathology Cognitive and Physical Markers With Age in Cognitively Normal Individuals Aged 60-102 Years.

Publications

Associations of Brain Pathology Cognitive and Physical Markers With Age in Cognitively Normal Individuals Aged 60-102 Years.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets