Search

The Cache County Study on Memory in Aging (CCSMA) and subsequent Dementia Progression Study (DPS) were two research studies that took place in Cache County, Utah. These studies followed 5092 participants aged 65 or older for approximately 12 years and looked at risk and protective factors for dementia, including Alzheimer’s disease. One of the factors investigated was genes that are known to influence brain health, such as brain-derived neurotrophic factor (BDNF), a protein found in the brain that helps with the survival of brain cells. BDNF genes have been shown to be associated with Alzheimer’s disease and related dementia (ADRD) risk, but little is known about the influence these genes have after dementia is diagnosed. The current study looked at how BDNF related genes were associated with learning and memory abilities (i.e. cognitive ability) and problematic behaviors (e.g. delusions, agitation/aggression, anxiety) in individuals from the CCSMA and DPS who were diagnosed with ADRD. This research is important to help understand what may contribute to often-seen differences in dementia progression and help inform possible treatment decisions. The results of the current project showed that BDNF genes influenced both progression of cognitive difficulties and problematic behaviors in individuals with ADRD. Additionally, it was shown that many of these effects depended on the sex of the individual, such that men and women progressed at different rates and were influenced by different BDNF related genotypes. These results provide evidence of the influence of BDNF genes after dementia diagnosis and highlights the need to investigate contributing factors related to the sex of the individual. Targeted medication or behavioral treatment of dementia that both improves BDNF function in the brain, as well as mitigates any sex-related effects, may also be another avenue for future research.

The Cache County Study on Memory in Aging (CCSMA) is a longitudinal population-based study which took place in Cache County, Utah. The study followed 5092 older-adult residents (aged 65+) for approximately 12 years to examine risk and protective factors for dementia. Participants completed dementia screening and follow-up assessments across four triennial visits. Additionally, researchers gathered information regarding demographics, reproductive history (e.g. age of menopause; hormone replacement therapy [HRT]) and other health-related factors, such as physical activity. Genotyping of DNA was completed for a genetic variation of genes for brain-derived neurotrophic factor (BDNF), a protein found in the brain associated with neuronal health and survival. Estrogen has been associated with cognitive health and has been shown to interact with BDNF in the brain to promote neuronal survival. The current research investigated the associations between estrogen, BDNF, and cognitive decline in older adult women from the CCSMA. An examination of how reproductive history, including the reproductive window (age of menarche to menopause) and use of HRT, affects the cognitive health of women in older adulthood can provide a clearer understanding of how estrogen exposure across the lifespan contributes to cognition in late life. This research can be helpful in determining the implications of events such as pregnancy, breastfeeding, surgical menopause and use of HRT on cognitive decline. Additionally, an investigation of how these reproductive factors interact with BDNF genetics is important to understand gene-by-environment interactions. The results of the current project demonstrated that increased lifelong estrogen exposure, both in the form of the reproductive window and HRT use, had small cognitive benefits for women in late life. Additionally, it was shown that women who initiated HRT use closer to menopause had increased cognitive status compared to those who initiated later. The specific BDNF gene under investigation was not associated with cognitive status in late life, neither was the interaction between BDNF and lifetime estrogen exposure. This research contributes to the discussion of sex-dependent factors of cognitive health and can help provide a better understanding late life cognitive decline.