The 2023 Alzheimer’s Awareness key theme was ‘never too early, never too late’, with a key focus on modifiable risk factors and risk reduction. Research in the nascent field of nutritional psychiatry continues to emerge, and the evidence base surrounding nutrition interventions, paired with lifestyle modifications, has yielded some interesting results with regards to Alzheimer’s prevention.

Diet and Lifestyle

Recent research by Jia et al. (2023) identified some modifiable diet and lifestyle  risk factors for dementia. Their study followed 29, 072 participants for a period of ten years in China, to explore dietary and lifestyle factors which may prevent memory decline in older adults. Over a fifth of participants also had the APOE4 allele, a key genetic risk factor for development of Alzheimer’s disease.  The study measured the following factors:

• a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items, including – fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, and tea)
• regular physical exercise (≥ 150 min of moderate intensity or ≥75 min of vigorous intensity, per week)
• active social contact (≥ twice per week)
• active cognitive activity (≥ twice per week), never or previously smoked, and never drinking alcohol.

Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination (MMSE). Results indicated that a healthy lifestyle was associated with a slower rate of memory decline, even in individuals with the APOE4 allele. Of all the factors assessed, healthy diet was indicated to be the most significantly protective factor (P<0.001), followed by, in order of statistical significance, active cognitive activity (P<0.001), regular physical exercise (P<0.001), active social contact (P<0.001), never or former smoker ( P=0.026), and never drinking alcohol (P=0.048).

 Keeping Key Biomarkers within Healthy Ranges

Adopting the aforementioned nutrition and lifestyle interventions may be beneficial for keeping some key biomarkers associated with Alzheimer’s disease within healthy ranges. Below some of these markers are briefly delineated in terms of findings from the literature.

Cholesterol

Lower HDL and higher triglyceride (a type of fat found in the blood) levels measured in blood in early adulthood, and high blood sugar levels in middle adulthood, have been indicated to contribute to future risk of developing Alzheimer’s. High LDL cholesterol has been indicated to increase accumulation of beta amyloid plaques in the brain, a key feature and driver of Alzheimer’s disease (Ferringa & Kant, 2021). However, a recent study observed that a 15 mg/dL increase in high density lipoprotein (HDL) cholesterol was associated with decreased AD risk during early (15.4%, P = 0.041) and middle (17.9%, P = 0.014) adulthood (Zhang et al., 2023).

 Homocysteine

Homocysteine has been established as an independent risk factor for Alzheimer’s disease (Sheshadri et al., 2002). Homocysteine is a sulphur containing intermediate metabolite produced during the metabolism of methionine (Met) to cysteine (Cys) (Kumar et al., 2017).   Both high and low homocysteine are associated with increased Alzheimer’s risk. Elevated homocysteine increases levels of inflammation in the body, has a detrimental impact on the structural integrity of blood vessels, and also affects gene expression (Ganguly & Alam, 2015; Li et al., 2015). Bae et al. (2021) highlighted in their research how overuse of vitamin supplements could increase risk, and be explanatory, of incidence of low homocysteine, whilst acknowledging that high homocysteine should be addressed with appropriate health interventions.

 Blood Glucose

Patients with type II diabetes who have poorly controlled blood glucose levels are at significantly increased risk of subsequent development of Alzheimer’s disease (Ngyuyen et al., 2020). High blood sugar causes inflammation. This may damage brain cells and cause Alzheimer’s disease to develop (Alzheimer’s Association, 2023). A prospective cohort study by Zhang et al. (2023) including 4,932 participants  demonstrated that a 15 mg/dL increase in glucose, measured during middle adulthood, was associated with 14.5% increased Alzheimer’s disease risk (P = 0.00029) (Zhang et al., 2023).

Blood Pressure

Research has indicated that higher blood pressure is associated with poorer memory scores. Having elevated blood pressure has been indicated to be predictive of worse cognitive ability for those who have the APOE4 allele, even in otherwise healthy midlife adults (Oberlin et al., 2015). The link between elevated blood pressure and Alzheimer’s disease is well established, and addressing hypertension early is key for reducing risk of developing the disease.

 Thyroid

Lempiere et al. (2022) found in their study that hypothyroidism was associated with an 81% increase in dementia risk. Although further research is required to explore the exact mechanisms, it appears that this link is mediated via the HPT (hypothalamic–pituitary–thyroid) axis, which is a bidirectional communication pathway between the brain and thyroid. Performing thyroid blood tests at regular intervals during midlife and older adulthood could be a supportive measure for identifying at risk individuals for Alzheimer’s disease.

References

Alzheimer’s association, 2023. Diabetes and Cognitive Decline. https://www.alz.org/media/documents/alzheimers-dementia-diabetes-cognitive-decline-ts.pdf

Appel, L. J., Moore, T. J., Obarzanek, E., Vollmer, W. M., Svetkey, L. P., Sacks, F. M., Bray, G. A., Vogt, T. M., Cutler, J. A., Windhauser, M. M., Lin, P. H., & Karanja, N. (1997). A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. The New England journal of medicine, 336(16), 1117–1124. Available at: <https://doi.org/10.1056/NEJM199704173361601> [Accessed 22/08/2022]

Bach-Faig, A., Berry, E. M., Lairon, D., Reguant, J., Trichopoulou, A., Dernini, S., Medina, F. X., Battino, M., Belahsen, R., Miranda, G., Serra-Majem, L., & Mediterranean Diet Foundation Expert Group. (2011). Mediterranean diet pyramid today. Science and cultural updates. Public health nutrition, 14(12A), 2274–2284. Available at: <https://doi.org/10.1017/S1368980011002515> [Accessed 22/08/2022]

Cappello, M., Morreale, G. C., & Licata, A. (2016). Elderly Onset Celiac Disease: A Narrative Review. Clinical medicine insights. Gastroenterology, 9, 41–49. https://doi.org/10.4137/CGast.S38454

Feringa, F. M., & van der Kant, R. (2021). Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects. Frontiers in aging neuroscience, 13, 690372. https://doi.org/10.3389/fnagi.2021.690372

Ganguly, P., & Alam, S. F. (2015). Role of homocysteine in the development of cardiovascular disease. Nutrition journal, 14, 6. https://doi.org/10.1186/1475-2891-14-6

Kumar, A., Palfrey, H. A., Pathak, R., Kadowitz, P. J., Gettys, T. W., & Murthy, S. N. (2017). The metabolism and significance of homocysteine in nutrition and health. Nutrition & metabolism, 14, 78. https://doi.org/10.1186/s12986-017-0233-z

Lebwohl, B., Luchsinger, J. A., Freedberg, D. E., Green, P. H., & Ludvigsson, J. F. (2016). Risk of dementia in patients with celiac disease: a population-based cohort study. Journal of Alzheimer’s disease : JAD, 49(1), 179–185. https://doi.org/10.3233/JAD-150388

Li, T., Chen, Y., Li, J., Yang, X., Zhang, H., Qin, X., Hu, Y., & Mo, Z. (2015). Serum Homocysteine Concentration Is Significantly Associated with Inflammatory/Immune Factors. PloS one, 10(9), e0138099. https://doi.org/10.1371/journal.pone.0138099

McEvoy, C. T., Guyer, H., Langa, K. M., & Yaffe, K. (2017). Neuroprotective Diets Are Associated with Better Cognitive Function: The Health and Retirement Study. Journal of the American Geriatrics Society, 65(8), 1857–1862. Available at: <https://doi.org/10.1111/jgs.14922> [Accessed 22/08/2022].

Morris, M. C., Tangney, C. C., Wang, Y., Sacks, F. M., Barnes, L. L., Bennett, D. A., & Aggarwal, N. T. (2015). MIND diet slows cognitive decline with aging. Alzheimer’s & dementia : the journal of the Alzheimer’s Association, 11(9), 1015–1022. Available at:<https://doi.org/10.1016/j.jalz.2015.04.011> [Accessed 22/08/2022]

Nguyen, T. T., Ta, Q. T. H., Nguyen, T. K. O., Nguyen, T. T. D., & Giau, V. V. (2020). Type 3 Diabetes and Its Role Implications in Alzheimer’s Disease. International journal of molecular sciences, 21(9), 3165. https://doi.org/10.3390/ijms21093165

Oberlin, L. E., Manuck, S. B., Gianaros, P. J., Ferrell, R. E., Muldoon, M. F., Jennings, J. R., Flory, J. D., & Erickson, K. I. (2015). Blood pressure interacts with APOE ε4 to predict memory performance in a midlife sample. Neuropsychology, 29(5), 693–702. https://doi.org/10.1037/neu0000177

Prince, MJ, Wimo, A, Guerchet, MM, Ali, GC, Wu, Y-T & Prina, M 2015, World Alzheimer Report 2015 – The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International, London.  Available at: <http://www.alz.co.uk/research/world-report-2015> [Accessed 22/08/2022]

Rashtak, S., & Murray, J. A. (2009). Celiac disease in the elderly. Gastroenterology clinics of North America, 38(3), 433–446. https://doi.org/10.1016/j.gtc.2009.06.005

Seshadri, S., Beiser, A., Selhub, J., Jacques, P. F., Rosenberg, I. H., D’Agostino, R. B., Wilson, P. W., & Wolf, P. A. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. The New England journal of medicine, 346(7), 476–483. https://doi.org/10.1056/NEJMoa011613

Zhang, X., Tong, T., Chang, A., Ang, T. F. A., Tao, Q., Auerbach, S., Devine, S., Qiu, W. Q., Mez, J., Massaro, J., Lunetta, K. L., Au, R., & Farrer, L. A. (2023). Midlife lipid and glucose levels are associated with Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association, 19(1), 181–193. https://doi.org/10.1002/alz.12641