Cognitive Resilience in Brain Health and Dementia Research

Abstract

With the expected rise in Alzheimer's disease and related dementias (ADRD) in the coming decades due to the aging population and a lack of effective disease-modifying treatments, there is a need for preventive strategies that may tap into resilience parameters. A wide array of resilience strategies has been proposed including genetics, socioeconomic status, lifestyle modifications, behavioral changes, and management of comorbid disease. These different strategies can be broadly classified as distinguishing between modifiable and non-modifiable risk factors, some of which can be quantified so that their clinical intervention can be effectively accomplished. A clear shift in research focus from dementia risk to addressing disease resistance and resilience is emerging that has provided new potential therapeutic targets. Here we review and summarize the latest investigations of resilience mechanisms and methods of quantifying resilience for clinical research. These approaches include identifying genetic variants that may help identify novel pathways (e.g., lipid metabolism, cellular trafficking, synaptic function, inflammation) for therapeutic treatments and biomarkers for use in a precision medicine-like regimen. In addition, innovative structural and molecular neuroimaging analyses may assist in detecting and quantifying pathological changes well before the onset of clinical symptoms setting up the possibility of primary and secondary prevention trials. Lastly, we summarize recent studies demonstrating the study of resilience in caregivers of persons living with dementia may have direct and indirect impact on the quality of care and patient outcomes.

Keywords: Alzheimer’s disease; biomarkers; brain health; cognition; cognitive reserve; dementia; neuroimaging; resilience.

Fig. 1.

Factors with positive and negative impact on cognitive resilience. The positive factors include cognitive reserve (education and occupation), positive lifestyles (diet, exercise, and cognitive activity), positive behaviors (mindfulness, optimism, and self-sufficiency), genetics (kdm6a, TREM2), greenspace (early and mid-life exposure to natural greenery), and socio-demographics (younger and high income). The negative factors are vascular risk factors (hypertension, diabetes, and obesity), negative lifestyles (head injury, smoking, and alcohol consumption), negative behaviors (depression and anxiety), genetics (MS4A6A, BDNF), co-morbidities (multiple medical conditions), and socio-demographics (low income, old age, racial/ethnic differences).