Clinical Manifestations

Over the past decades, many risk factors for dementia have been identified including sensory and motor functions. Established risk scores to predict onset of cognitive impairment and/or dementia (e.g., the CAIDE and Framingham Risk Score) often focused on cardiovascular risk factors and have not been updated in more recent generations. Risk scores for asymptomatic middle-aged people, which are based on practical test batteries will be useful for targeted population screenings. The aim of this study was to construct a parsimonious risk prediction model of 10-year cognitive decline and impairment using factors measured in midlife in a current cohort. This longitudinal study is based on N = 1529 (54% women, mean age 49 years) Beaver Dam Offspring Study participants with data from baseline, 5-year and 10-year follow-up. We assessed objectively measured and self-reported hearing, vision, olfactory, and motor function, lifestyle, cardiovascular and general health factors, and blood-based markers of inflammation, neurodegeneration, and amyloid. We determined 10-year cognitive decline (trail-making test B time;10% most decline) and cognitive impairment (neurocognitive case review). We constructed least absolute shrinkage and selection operator (LASSO) logistic regression models with 10-fold cross-validation and evaluated predictive ability via receiver operating characteristic curves (AUCs). The effect selection percentage indicated the percentage of times specific predictors were selected in the n = 100 bootstrapped samples of models and was used to establish final models. There were N = 121 cognitive decline and N = 217 cognitive impairment cases. The six top predictors for cognitive decline (age, income, fine-motor skill performance, olfactory function, peripheral artery disease, serum neurofilament light chain protein (NfL)) and for cognitive impairment (sex, fine-motor skill performance, olfactory function, self-rated vision, alcohol consumption, NfL) yielded models with an AUC of 0.80(95% confidence interval:[0.76-0.83]) and 0.73[0.69-0.77], respectively. In middle-aged adults, measures of sensory and motor function and NfL were among the best predictors of 10-year onset of cognitive decline and impairment and only 6 factors were needed to achieve acceptable to excellent AUCs. Cross-validation in another cohort is needed to verify these factors as reliable and valid predictors to identify those at high risk for neurodegeneration and cognitive decline who cou