Evidence-Based Reviews

Lowering risk of Alzheimer’s disease

Current Psychiatry. 2010 June;9(6):23-35

References

1. Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the systolic hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002;162:2046-2052.

2. Tzourio C, Anderson C, Chapman N, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163:1069-1075.

3. Peters R, Beckett N, Forette F. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG). Lancet Neurol. 2008;7(8):683-689.

4. Rea TD, Breitner JC, Psaty BM, et al. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol. 2005;62:1047-1051.

5. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.

6. Kulbertus H, Scheen AJ. [The PROSPER Study (PROspective study of pravastatin in the elderly at risk)]. Rev Med Liege. 2002;57(12):809-813.

7. Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956-964.

8. McGuinness B, Bullock R, Craig D, et al. Statins for the treatment of Alzheimer’s disease and dementia (protocol). Cochrane Database Syst Rev. 2009;1:CD007514.-

9. Abbatecola AM, Rizzo MR, Barbieri M, et al. Postprandial plasmaglucose excursions and cognitive functioning in aged type 2 diabetics. Neurology. 2006;67:235-240.

10. Munshi M, Grande L, Hayes M, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care. 2006;29:1794-1799.

11. Ott A, Stolk RP, van Harskamp F, et al. Diabetes mellitus and the risk of dementia. The Rotterdam study. Neurology. 1999;53:1937-1942.

12. Reitz C, Luchsinger J, Tang MX, et al. Effect of smoking and time on cognitive function in the elderly without dementia. Neurology. 2005;65:870-875.

13. Reitz C, den Heijer T, van Duijn C, et al. Relation between smoking and risk of dementia and Alzheimer disease: the Rotterdam Study. Neurology. 2007;69:998-1005.

14. Miller ER, III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46.

15. Boothby LA, Doering PL. Vitamin C and vitamin E for Alzheimer’s disease. Ann Pharmacother. 2005;39(12):2073-2080.

16. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369:208-216.

17. Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003;60:940-946.

18. Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006;63:1545-1550.

19. Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol. 1997;42:776-782.

20. van Gelder BM, Tijhuis M, Kalmijn S, et al. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr. 2007;85:1142-1147.

21. Solfrizzi V, Capurso C, Panza F. Adherence to a Mediterranean dietary pattern and risk of Alzheimer’s disease. Ann Neurol. 2006;60:620.-

22. Scarmeas N, Luchsinger JA, Mayeux R, et al. Mediterranean diet and Alzheimer disease mortality. Neurology. 2007;69(11):1084-1093.

23. Kivipelto M, Rovio S, Ngandu T, et al. Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. J Cell Mol Med. 2008;12(6B):2762-2771.

24. Podewils LJ, Guallar E, Kuller LH, et al. Physical activity, APOE genotype and dementia risk: findings from the Cardiovascular Health Cognition Study. Am J Epidemiol. 2005;161:639-651.

25. Hall CB, Derby C, LeValley A, et al. Education delays accelerated decline on a memory test in persons who develop dementia. Neurology. 2007;69:1657-1664.

26. Wang HX, Karp A, Winblad B, et al. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen Project. Am J Epidemiol. 2002;155:1081-1087.

27. Scarmeas N, Levy G, Tang MX, et al. Influence of leisure activity on the incidence of Alzheimer’s disease. Neurology. 2001;57:2236-2242.

28. Willis SL, Tennstedt SL, Marsiske M, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006;296:2805-2814.

29. Guo Z, Cupples LA, Kurz A, et al. Head injury and the risk of AD in the MIRAGE study. Neurology. 2000;54:1316-1323.

30. Ruitenberg A, van Swieten JC, Witteman JC, et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet. 2002;359:281-286.

In the absence of evidence from RCTs, we cannot recommend alcohol to reduce the risk of AD.

Lifestyle and activity

Three components of lifestyle—social, mental, and physical activity—are inversely associated with the risk for dementia, AD, and cognitive impairment.

Physical exercise has been thought to enhance brain neurotrophic factor and modify apoptosis. Exercise can deter stroke and microvascular disease and improve regional cerebral blood flow. In the Cardiovascular Health Study, participants who expended the highest quartile of energy had a lower risk of all-cause dementia and AD compared with participants who expended the lowest quartile of energy.²⁴

Clinical Point

Physical exercise is believed to enhance brain neurotrophic factor and modify apoptosis, and can deter stroke

Mental and social activity. Epidemiologic studies have shown associations between higher educational achievement and other socioeconomic factors and reduced AD risk. Advanced education is believed to represent a cognitive reserve that delays presentation of AD’s effects on memory and cognitive function, rather than providing a protective effect against accumulation of AD pathology. Higher-educated individuals appear to experience a somewhat more rapid rate of cognitive decline when AD does become apparent, perhaps because they have accumulated a greater degree of AD pathology at that point compared with less-educated persons.

Among 117 persons with dementia in the Bronx Aging Study, each additional year of formal education delayed the time of accelerated decline by 0.21 years. After accelerated decline began, each year of additional formal education was associated with a slightly faster rate of memory decline.²⁵

Clinical Point

Higher levels of leisure activity and daily mentally stimulating activities are associated with decreased risk of Alzheimer’s disease

The longitudinal, population-based Kungsholmen Project in Stockholm, Sweden, found an association between daily mentally stimulating activities and decreased risk of all-cause dementia.²⁶ Similarly, higher levels of leisure activity were linked to reduced risk of all-cause dementia in a longitudinal study of 1,772 persons age ≥65 living in Manhattan, NY.²⁷ In a randomized, single-controlled study of the long-term effects of cognitive training, elderly individuals from 6 U.S. cities showed sustained improvement in specific cognitive performance up to 5 years after training sessions began, including memory, reasoning, and speed of processing.²⁸

It seems reasonable to encourage older patients to maintain or increase physical, cognitive, and leisure activities as well as social interaction. These interventions can improve the quality of life and lower the risk of depression, which may be a response to cognitive decline or an independent risk factor for dementia (Box 3). The Table lists “brain exercises” you can suggest to patients to increase their mental and social activity.

Clinical Point

Evidence of a link between head trauma and AD risk is inconclusive

Head trauma. The Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) project found an association between AD risk and a history of head trauma, especially in persons with APOE e4 alleles.²⁹ Conversely, the Rotterdam Study showed no change in dementia risk for persons with a history of head trauma.³⁰

Even in the absence of conclusive evidence supporting AD prevention, protecting the head by buckling seat belts while driving, wearing helmets when participating in sports, and “fall-proofing” the home is recommended.

Box 3

Is depression an independent risk factor for dementia?

Depression often occurs before or as a coexisting condition with Alzheimer’s disease (AD).^a Although depression has been considered a response to cognitive decline or an early manifestation of dementia,^b it also could be an independent risk factor.^c,d

The pathologic mechanism linking depression and subsequent dementia is not well understood. Hypotheses include an indirect neurotoxic effect of depression mediated by cortisol-induced hippocampal atrophy or lowered brain-derived neurotrophic factor levels.^e Depression and dementia might share genetic links, although a cohort study of 404 individuals with AD detected no association between apolipoprotein E genotypes or alleles and depressive symptoms.^f

References
a. Lupien SJ, Nair NP, Brière S, et al. Increased cortisol levels and impaired cognition in human aging: implication for depression and dementia in later life. Rev Neurosci. 1999;10(2):117-139.
b. Preuss UW, Siafarikas N, Petrucci M, et al. Depressive disorders in dementia and mild cognitive impairments: is comorbidity a cause or a risk factor? Fortschr Neurol Psychiatr. 2009;77:399-406.
c. Green RC, Cupples LA, Kurz A, et al. Depression as a risk factor for Alzheimer disease: the MIRAGE Study. Arch Neurol. 2003;60(5):753-759.
d. Ownby RL, Crocco E, Acevedo A, et al. Depression and risk for Alzheimer’s disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006;63(5):530-538.
e. Meeks TW, Ropacki SA, Jeste DV. The neurobiology of neuropsychiatric syndromes in dementia. Curr Opin Psychiatry. 2006;19(6):581-586.
f. Craig D, Hart DJ, McIlroy SP, et al. Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;19(2-3):154-157.