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Prediction models for dementia and neuropathology in the oldest old: the Vantaa 85+ cohort study.

Abstract：

BACKGROUND:We developed multifactorial models for predicting incident dementia and brain pathology in the oldest old using the Vantaa 85+ cohort. METHODS:We included participants without dementia at baseline and at least 2 years of follow-up (N = 245) for dementia prediction or with autopsy data (N = 163) for pathology. A supervised machine learning method was used for model development, considering sociodemographic, cognitive, clinical, vascular, and lifestyle factors, as well as APOE genotype. Neuropathological assessments included β-amyloid, neurofibrillary tangles and neuritic plaques, cerebral amyloid angiopathy (CAA), macro- and microscopic infarcts, α-synuclein pathology, hippocampal sclerosis, and TDP-43. RESULTS:Prediction model performance was evaluated using AUC for 10 × 10-fold cross-validation. Overall AUCs were 0.73 for dementia, 0.64-0.68 for Alzheimer's disease (AD)- or amyloid-related pathologies, 0.72 for macroinfarcts, and 0.61 for microinfarcts. Predictors for dementia were different from those in previous reports of younger populations; for example, age, sex, and vascular and lifestyle factors were not predictive. Predictors for dementia versus pathology were also different, because cognition and education predicted dementia but not AD- or amyloid-related pathologies. APOE genotype was most consistently present across all models. APOE alleles had a different impact: ε4 did not predict dementia, but it did predict all AD- or amyloid-related pathologies; ε2 predicted dementia, but it was protective against amyloid and neuropathological AD; and ε3ε3 was protective against dementia, neurofibrillary tangles, and CAA. Very few other factors were predictive of pathology. CONCLUSIONS:Differences between predictors for dementia in younger old versus oldest old populations, as well as for dementia versus pathology, should be considered more carefully in future studies.

journal_name

Alzheimers Res Ther

journal_title

Alzheimer's research & therapy

authors

Hall A,Pekkala T,Polvikoski T,van Gils M,Kivipelto M,Lötjönen J,Mattila J,Kero M,Myllykangas L,Mäkelä M,Oinas M,Paetau A,Soininen H,Tanskanen M,Solomon A

doi

10.1186/s13195-018-0450-3

subject

Has Abstract

pub_date

2019-01-22 00:00:00

pages

issue

issn

1758-9193

pii

10.1186/s13195-018-0450-3

journal_volume

pub_type

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Prediction models for dementia and neuropathology in the oldest old: the Vantaa 85+ cohort study.