Recent work by DUPRI Scholars within the Biodemography of Aging Unit (BARU)—including Igor Akushevich, Konstantin Arbeev, Eric Stallard, Svetlana Ukraintseva, Anatoliy Yashin, and Arseniy Yashkin—examines the complex interplay between infections, vaccinations, genetics, and cognitive decline, including Alzheimer's disease (AD) and other dementias, in older adults.
A study in Experimental Gerontology using Health and Retirement Study (HRS) data found that shingles, pneumonia, and recurrent mycoses diagnosed between ages 65 and 75 were associated with a significantly increased risk of Alzheimer's disease (AD) later in life, while pneumococcal and shingles vaccines administered during the same age period were associated with a significantly lower risk of AD. This suggests that compromised immunity may play a role in AD development.
Another study in PLoS ONE using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data explored the interplay between infections and APOE4, a genetic risk factor for AD, and concluded that infections and APOE4 jointly contribute to brain glucose hypometabolism, a biomarker of AD pathology, supporting a "multi-hit" mechanism in AD development.
Finally, a study in BMC Neurology, also using ADNI data, investigated the influence of the SNP rs6859 in the NECTIN2 gene on cognitive decline trajectories, identifying distinct patterns of decline and suggesting that genetic variability in NECTIN2 may contribute to the heterogeneity of cognitive decline in older adults.
This work collectively highlights the multifaceted nature of cognitive decline and AD. It suggests:
- A potential link between the body's interaction with pathogens and the development of AD. Infections in later life appear to increase AD risk, possibly due to compromised immunity and neuroinflammation.
- A potential protective role of certain vaccinations (shingles and pneumococcal) against AD. This could be due to heterologous immune effects or by preventing infection-related neuroinflammation.
- The importance of genetic factors in modulating the risk and trajectory of cognitive decline. The NECTIN2 gene variant rs6859 is shown to be associated with both baseline cognitive function and different patterns of cognitive decline over time. The APOE4 genotype interacts with the effects of infections on brain metabolism.
- Brain glucose hypometabolism as a potential mediator. Infections are associated with increased brain hypometabolism, a key feature of AD, and this effect is amplified in individuals with the APOE4 risk allele.