Neurodegeneration — 6

The importance of sleep for brain health is well established. As we’ve discussed, it is during sleep that our metabolic waste products are cleared through cerebrospinal fluid and the glymphatic system. Even a single sleepless night in young individuals has demonstrated accumulation of Aβ. A UK Biobank study in over 150,000 participants, 48,000 of whom underwent brain imaging, with cognitive testing and six- to ten-year follow-up, indicated that seven hours of sleep linked peak cognitive performance and preserved brain structure. Multiple studies in midlife (fig. 7.3) and older adults indicate that sleep disturbance is a risk for late-onset dementia. Note again the seven-hour cutoff for association with the lowest hazard ratio. It’s a surprising result. After seven hours, more sleep is associated with more risk.

Figure 7.3. The relationship of sleep duration and risk of dementia. Adapted from Severine Sabia et al., “Association of sleep duration in middle and old age with incidence of dementia,” Nature Communications 12, no. 1 (April 2021): 2289, https://doi.org/10.1038/s41467-021-22354-2.

Other cardiovascular factors are tied to risk of Alzheimer’s and all-cause dementia, including a very high HDL, high LDL, and elevation of systolic blood pressure. The quality and quantity of daily social encounters have exhibited a strong inverse association with risk of Alzheimer’s. In people at high risk for Alzheimer’s, a randomized trial subgroup analysis showed the benefit of audiological counseling and hearing aids to reduce three-year cognitive decline. From the United Kingdom Ageing Cohort, the relationship between musicality and cognitive function was highlighted. Playing an instrument and singing were associated with preserved memory and executive function.

The role of the environment is receiving more attention for increasing the risk of Alzheimer’s, with multiple studies reinforcing the impact of air pollution. At autopsy of 224 participants with Alzheimer’s disease, traffic-related particulate matter correlated with a near doubling of risk, prominently among people without the APOE4 alleles. Using explainable AI, a deep dive of the relationship between air pollution and Alzheimer’s in Italy revealed that ozone and nitrogen dioxide were the main pollutant contributors. Beyond air pollution, on the basis of epigenetic changes, concerns have been raised on various metals (cadmium, arsenic, lead, aluminum, mercury, nickel, and manganese), aflatoxin B1 found in some foods, endocrine-disrupting chemicals (bisphenol A and polybrominated biphenyls), pesticides, alcohol, and tobacco. The concern over the pervasive presence of microplastics and nanoplastics, which we inhale and ingest, and which can circulate in our bloodstream, has recently been amplified by finding these in our brains. These plastics have an alarming capacity to incite inflammation there. Pervasive environmental chemicals, such as the quaternary chemical compounds found in disinfection agents and personal care products, or organophosphate flame retardants in furniture and electronics, have been shown to impair oligodendrocyte cell development. An extensive study of the modifiable factors associated with brain aging showed that diabetes, pollution, and alcohol intake were the most deleterious risk factors. The 2024 Lancet Commission Report on Dementia, which added untreated vision loss and high LDL cholesterol as modifiable risk factors, estimated that 45 percent of dementia can be prevented or significantly delayed. Based on the data reviewed here on sleep health, unprocessed food intake, and risk after severe COVID in older adults, that raises the number of factors to seventeen, so perhaps up to half of the burden of dementia can be substantially reduced with attention to these risks (fig. 7.4).