Journal
ALZHEIMERS RESEARCH & THERAPY
Volume 11, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13195-018-0450-3
Keywords
Dementia; Neuropathology; Oldest old; Prediction; Supervised machine learning
Categories
Funding
- European Union 7th Framework Program for research, technological development, and demonstration VPH-DARE@IT [601055]
- MIND-AD Academy of Finland [291803]
- Swedish Research Council [2017-06105, 529-2014-7503]
- University of Eastern Finland
- Kuopio University Hospital
- Academy of Finland [287490, 294061, 278457, 319318]
- Center for Innovative Medicine (CIMED) at Karolinska Institutet Sweden
- Stiftelsen Stockholms sjukhem Sweden
- Knut and Alice Wallenberg Foundation (Sweden)
- Konung Gustaf V:s och Drottning Victorias Frimurarstiftelse Sweden
- Alzheimerfonden Sweden
- Stockholm County Council [ALF 20150589, 20170304]
- UEF Bioinformatics computing infrastructure
- HUS ERVA fund
- Swedish Research Council [2017-06105] Funding Source: Swedish Research Council
- Academy of Finland (AKA) [291803] Funding Source: Academy of Finland (AKA)
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BackgroundWe developed multifactorial models for predicting incident dementia and brain pathology in the oldest old using the Vantaa 85+ cohort.MethodsWe 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 -amyloid, neurofibrillary tangles and neuritic plaques, cerebral amyloid angiopathy (CAA), macro- and microscopic infarcts, -synuclein pathology, hippocampal sclerosis, and TDP-43.ResultsPrediction model performance was evaluated using AUC for 10x10-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: epsilon 4 did not predict dementia, but it did predict all AD- or amyloid-related pathologies; epsilon 2 predicted dementia, but it was protective against amyloid and neuropathological AD; and epsilon 3 epsilon 3 was protective against dementia, neurofibrillary tangles, and CAA. Very few other factors were predictive of pathology.ConclusionsDifferences 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.
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