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Prevention of dementia

Prevention of dementia
Authors:
Daniel Press, MD
Zoe Arvanitakis, MD, MS, EMBA
Section Editors:
Steven T DeKosky, MD, FAAN, FACP, FANA
Kenneth E Schmader, MD
Deputy Editors:
Janet L Wilterdink, MD
Jane Givens, MD, MSCE
Literature review current through: May 2025. | This topic last updated: May 15, 2025.

INTRODUCTION — 

Dementia is an increasing problem as the global population ages. There are currently an estimated 55 million people worldwide with dementia, and this number is projected to increase to 115 million by 2050 [1,2].

This topic discusses interventions to prevent cognitive decline and dementia in adults without baseline cognitive impairment. Other aspects related to cognitive decline and dementia, including risk factors, evaluation, and management, are discussed separately:

●(See "Risk factors for cognitive decline and dementia".)

●(See "Evaluation of cognitive impairment and dementia".)

●(See "Mild cognitive impairment: Prognosis and treatment".)

●(See "Management of the patient with dementia".)

RATIONALE — 

Asymptomatic individuals often present with concerns about developing dementia, especially when they have a family history of the disease.

Some reports of the literature on risk factors for dementia support the impact of risk factor modification on dementia incidence, although other reports differ [3-6]. Many risk factors for dementia, such as hypertension or diabetes, warrant treatment to reduce the risk of other clinical outcomes. Whether such treatment also reduces the risk of dementia is, in most cases, uncertain. The overall evidence does not support any single intervention as effective in delaying or preventing dementia [7,8]. However, some organizations are optimistic that intensive risk factor modification, especially during midlife (age 45 to 65 years), has the potential to delay or prevent a substantial number of dementia cases worldwide [4,5]. Some observational data support this idea; however, trials studying multimodality interventions have been of insufficient size and/or duration to demonstrate this [9-14].

Although population-based data are not entirely consistent, it does appear that the incidence of all-cause dementia, and especially vascular dementia, is declining in high-income countries over the past several decades [15-20]. This trend has occurred as the prevalence of many vascular risk factors has also decreased over time [15].

INTERVENTIONS THAT TREAT BASELINE CONDITIONS

Vascular risk factor modification — Trials demonstrating the beneficial effect of vascular risk factor modification on dementia prevention are lacking. Further, a few large trials of multimodal interventions that target several vascular risk factors have not demonstrated beneficial clinical outcomes; however, this is challenging to study as long-term follow-up data over decades are needed [10,11].

Vascular risk factor management as it relates specifically to primary and secondary vascular dementia prevention is discussed in more detail separately. (See "Treatment of vascular cognitive impairment and dementia", section on 'Vascular risk modification'.)

Treatment of hypertension — Hypertension appears to be associated with an increased risk of both vascular dementia and Alzheimer disease (AD), but the effect of antihypertensive treatment on reducing the risk of dementia or cognitive impairment is uncertain [3,21,22]. Studies that have identified hypertension as a risk factor for dementia and cognitive impairment are discussed separately. (See "Risk factors for cognitive decline and dementia", section on 'Hypertension'.)

No single randomized clinical trial has demonstrated a clear benefit for antihypertensive therapy in the risk of incident dementia or cognitive decline [21,23-31]. In a meta-analysis of four placebo-controlled clinical trials, antihypertensive therapy was associated with a nonsignificant reduction in incident dementia (3.0 versus 3.3 percent; odds ratio [OR] 0.89, 95% CI 0.72-1.09) [32]. Among clinical trials that evaluated cognitive decline using the Mini-Mental State Examination (MMSE), there was a modest benefit for antihypertensive treatment. The fact that these findings were not robust may be due to several factors: Some individual trials had an inadequate length of follow-up (which ranged from two to five years), many patients did not achieve significant blood pressure reduction, and some trials used relatively high blood pressure targets. Another meta-analysis, which examined trials in which an overall ≥10 mmHg difference in systolic blood pressure was observed between study groups, estimated that blood pressure treatment was associated with relative risk reduction in incident dementia of 0.88 (95% CI 0.78-0.98) [33]. In the SPRINT trial, intensive blood pressure treatment (goal systolic pressure <120 mmHg) was associated with reduced incidence of mild cognitive impairment (6.1 versus 7.5 percent) over a median follow-up of 5.1 years but not with a reduced incidence of dementia [31].

To date, data do not support an advantage of one particular antihypertensive agent over another [26,34,35]. A network meta-analysis of randomized and observational studies in patients without prior cerebrovascular disorders found that angiotensin receptor blockers had greater positive effects on cognition than did other classes [36]. The effect size was small, however, and no benefit was seen with longer treatment duration (ie, greater than six months). By contrast, when trials of diuretics and/or calcium channel blockers (DIU/CCB) were considered separately from angiotensin-converting enzyme inhibitors and angiotensin receptor blocking drugs (ACE/ARB) in a 2011 meta-analysis, there was a small but statistically significant reduction in dementia risk for DIU/CCB versus placebo (OR 0.88, p = 0.02; absolute risk difference 0.4 percent) but not for ACE/ARB (OR 1.01) [29].

The management of hypertension is discussed separately. (See "Overview of hypertension in adults".)

Diabetes management — Diabetes is a risk factor for cognitive decline and dementia and has been associated with both Alzheimer and vascular dementia [4]. (See "Risk factors for cognitive decline and dementia", section on 'Diabetes mellitus'.)

However, there are limited data regarding the effect of diabetes treatment on cognitive outcomes [37-39]. In a 2017 systematic review, no evidence was found that any specific treatment or treatment strategy was associated with reduced incident dementia or with better cognitive outcomes [37]. In a subsequently published trial of pioglitazone in patients at risk for AD, rates of cognitive impairment at five years were similar among those who received pioglitazone compared with placebo (3.3 versus 2.7 percent; hazard ratio [HR] 0.80, 99% CI 0.45-1.40) [40].

Observational studies suggest that specific diabetes treatments may be more helpful than others, but this requires confirmation in randomized studies. For example, in one longitudinal study in older people without dementia, metformin was associated with slower cognitive decline compared with nonusers [41]. One large electronic health record study examined incident dementia in patients >50 years old with type 2 diabetes [42]. Those treated with either a glucagon-like peptide 1 (GLP-1) receptor agonist or a sodium-glucose cotransporter 2 (SGLT2) inhibitor had lower rates of dementia compared with those treated with other glucose-lowering drugs (respective HRs: HR 0.67 [95% CI 0.47-0.96] and HR 0.57 [95% CI 0.43-0.75]). (See "Risk factors for cognitive decline and dementia", section on 'Diabetes mellitus'.)

For older adults, in particular, any potential beneficial effect of tight glucose control, which is of unproven benefit for dementia risk, must be balanced with the larger concerns for hypoglycemia in this population, which have resulted in more permissive glycated hemoglobin (A1C) goals. (See "Treatment of type 2 diabetes mellitus in the older patient", section on 'Avoiding hypoglycemia'.)

Statins for lipid lowering — Although a preventive effect of statins has been hypothesized based upon several mechanisms [43-50], there is no established role for the use of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) in the prevention of dementia [51].

While retrospective studies have shown an association between statin use and reduced risk of dementia, prospective observational studies have had mixed results regarding the efficacy of current or past statin use in reducing the incidence of dementia, the degree of age-related cognitive decline, or the neuropathologic burden of Alzheimer pathology [52-65]. In some studies, but not in others, the observed efficacy was linked to lipid lowering [58,60]. Other studies have suggested that statins may cause cognitive dysfunction in selected patients. (See "Statins: Actions, side effects, and administration", section on 'Behavioral and cognitive'.)

Data from two large randomized, controlled clinical trials of more than 25,000 patients with cardiovascular disease did not show any protective effect of statins for cognition [66,67], but these studies were not designed to identify dementia, and treatment was started relatively late in life, possibly after the pathogenic process was already in progress.

Treatment of hearing loss with hearing aids — Hearing loss has been associated with dementia in population-based studies and is recognized as an important potentially modifiable dementia risk factor [4]. (See "Risk factors for cognitive decline and dementia", section on 'Hearing loss'.)

Large prospective studies have suggested that use of hearing aids was protective against cognitive decline and dementia incidence [68-70]. Small randomized trials with relatively short follow-up have not conclusively confirmed or ruled out a benefit [71,72].

Herpes zoster vaccination — Herpes zoster, a neurotropic virus, has been speculated to play a role in the pathogenesis of dementia; this is unproven.

A number of observational studies have suggested that zoster vaccination may reduce the risk of dementia [73,74]. The results of one meta-analysis of observational studies suggested that herpes zoster vaccination reduces the risk of dementia (OR 0.76, 95% CI 0.60-0.96) [74]. Further evidence of a protective effect from the zoster vaccine comes from two large database studies in Wales and Australia [75,76]. These studies evaluated the impact of vaccination programs implemented in 2013 and 2016, each of which had specific age-based eligibility (individuals 70 to 79 years were eligible; those >80 years were not). Using regression discontinuity analysis, each study estimated that eligibility for the vaccination increased the absolute incidence of receiving the vaccine by 47.2 and 16.4 percent while reducing the absolute incidence of a dementia diagnosis by 1.3 percent (95% CI 0.2-2.7) and 1.8 percent (95% CI 0.4-3.3) over 7 to 7.5 years of follow-up.

HEALTHY LIFESTYLE INTERVENTIONS — 

People at risk for dementia are encouraged to maintain or increase physical activity and engage in social interaction. This recommendation is based on observational studies and biologic plausibility regarding the relationship between a healthy lifestyle and dementia risk (as well as other health benefits) [77-101].

Physical exercise — It is reasonable to encourage regular physical exercise in individuals concerned about their risk of dementia; however, the protective effects of exercise regarding dementia risk remain unproven. Although a number of observational studies have found an inverse association between physical exercise and risk of dementia, it is uncertain whether the relationship is causal [3,102-108].

In a meta-analysis of 12 randomized trials, aerobic exercise in healthy older adults did not improve cognitive outcomes in any domain, even in trials in which cardiorespiratory fitness improved in the exercise group [102]. The short duration of the trials (two to six months) likely contributed to this negative result. However, two trials of more prolonged (2 to 10 years) and intensive lifestyle interventions in sedentary older adults and adults with type 2 diabetes also found no improvement in cognitive function or rates of cognitive decline and dementia [109,110].

Exercise in early and middle adulthood, particularly if sustained over time, may have a greater chance of influencing dementia risk than exercise in late adulthood does. In particular, midlife levels of cardiorespiratory fitness may predict risk of dementia later in life, independent of cerebrovascular disease [111]. However, observational studies examining this question have had mixed results, with some [100,112] but not all [113] suggesting a benefit.

Social engagement — Social engagement is generally thought to be of benefit for all patients, and there is some evidence that social isolation may increase the risk of dementia. (See "Risk factors for cognitive decline and dementia", section on 'Social isolation' and "Geriatric health maintenance", section on 'Social isolation and loneliness'.)

In one systematic review of observational studies, individuals with high engagement in social activity and large social networks appeared to have better cognitive function [114]. While other studies support this finding, the nature of the association is unclear and no studies have examined the impact of any specific intervention [115-118].

Healthy diet — Some data suggest that a Mediterranean or similar diet may be beneficial for reducing dementia risk, but this is uncertain [119].

●Mediterranean diet – There is no single Mediterranean diet; however, such diets are typically high in fruits, vegetables, whole grains, beans, nuts, and seeds and include olive oil as an important source of fat. There are typically low to moderate amounts of fish, poultry, and dairy products, and little red meat. Adherence to a Mediterranean diet has been associated with improved cardiovascular outcomes, including stroke; it is hypothesized that these effects may promote lower dementia risk [120,121]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)", section on 'Diet' and "Healthy diet in adults", section on 'Mediterranean diet'.)

Observational studies using dietary questionnaires to assess and quantify adherence to the diet in different population cohorts have found that patients who were most adherent to the diet had a lower incidence of mild cognitive impairment and Alzheimer disease (AD) and slower rates of cognitive decline compared with those who did not follow this diet [77,122-128]. Similar benefits have been reported for those who are adherent to a modified Mediterranean diet that places particular emphasis on plant-based foods [129].

●MIND diet – The MIND diet is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet; it is primarily plant- and fish-based, and also limits dairy products. Observational data suggest that it is associated with lower rates of incident dementia [130].

A relatively short-term (three-year) randomized trial in older adults with a family history of dementia evaluated the MIND diet; changes in global cognition scores were not different between the intervention and control groups [131].

Moderation of alcohol intake — Individuals should avoid heavy alcohol intake, which is associated with increased risk of dementia. (See "Overview of the chronic neurologic complications of alcohol".)

While there is some evidence that light to moderate alcohol use may be protective relative to abstention, this is largely based on observational studies, and the findings have been inconsistent. These data are presented separately. (See "Overview of the risks and benefits of alcohol consumption", section on 'Dementia'.)

COGNITIVE ACTIVITIES

●Cognitive training – Various cognitive interventions, including memory training, the use of external memory cues, and organizational aids, have shown positive short-term effects on cognition in healthy older adults, but clinically important and long-term impacts on dementia risk are less clear [3,12,132-135]. Cognitive training should be approached with an awareness that individuals interested in dementia preventive measures, as well as their family/friends, may place undue hope on these interventions, which can result in increased stress and anxiety for the people affected. Thus, we encourage those activities that are enjoyable and engaging and do not push activities that are stressful or monotonous.

A number of studies have looked at interventions targeting specific cognitive domains (eg, speed-of-processing, episodic memory, inductive reasoning) with favorable results; however, the impact on important clinical outcomes over the long term remains uncertain [134,136-139]. One systematic review identified those features of cognitive programs that appeared to enhance their efficacy: a minimum duration of treatment (at least 10 weeks of initial treatment with periodic maintenance over follow-up), targeting more than one cognitive skill, implementation in a group format, and inclusion of other components related to quality of life (eg, physical activity, social interaction) [140].

Other randomized studies have examined cognitive training as part of multidomain interventions; as examples, the FINGER trial tested a multidomain intervention that included diet, exercise, cognitive training, and vascular risk monitoring, while the Multidomain Alzheimer Preventive Trial (MAPT) tested a multidomain intervention of physical activity, cognitive training, and nutritional advice with or without omega-3 fatty acid supplementation [12-14]. While studies are ongoing, the results to date do not conclusively demonstrate an impact on cognitive decline or dementia.

●Role of educational level and cognitive reserve – Higher levels of education have consistently been associated with a reduced risk of dementia, or at least a later onset of symptoms relative to neuropathologic disease burden [141-145]. However, advanced education is believed to represent a higher cognitive reserve that decreases the impact of degenerative pathology on cognitive function, rather than provide a direct protective effect against the accumulation of amyloid or other pathologic changes [143,146-149].

The beneficial effect of cognitive reserve may be most significant for executive functions early in decline [150]. Once clinical dementia develops, however, patients with higher education or occupational levels appear to experience a somewhat more rapid cognitive decline, at least in part because they are assumed to have accumulated a greater degree of Alzheimer pathology by the time dementia is apparent, compared with those with less education [151-153].

NO ROLE FOR DIETARY SUPPLEMENTATION OR HERBAL REMEDIES — 

While many dietary supplements and herbal remedies have been postulated to prevent dementia, there is little if any supporting evidence [154,155].

Vitamin E and other antioxidant vitamins — Oxidative stress may be important in the pathogenesis of Alzheimer disease (AD) and other causes of dementia, and some observational studies have found an association between higher dietary intake of antioxidants and lower risk of AD [156-165]. These findings have led to an interest in assessing the role of supplemental antioxidants for the prevention of AD.

However, in multiple large randomized clinical trials in older individuals with normal cognition or mild cognitive impairment, supplementation with a variety of antioxidant vitamins, including vitamin E, vitamin C, beta-carotene, and selenium, has shown no impact on cognitive change or incident dementia over follow-up times that have ranged from 7 to 10 years [166-171].

Further, since there are potential risks of vitamin E supplementation, we do not recommend supplementation with vitamin E or other antioxidants for the prevention of AD or other types of dementia. (See "Vitamin intake and disease prevention".)

The potential benefit of vitamin E in slowing disease progression in patients with established AD is discussed separately. (See "Treatment of Alzheimer disease", section on 'Antioxidants'.)

Vitamins B6, B12, and folate — While there is some evidence that elevated serum homocysteine and/or low serum levels of folate, vitamin B6, and vitamin B12 may be associated with impaired cognition and risk of dementia, there is no convincing evidence that vitamin supplementation prevents dementia [172]. (See "Risk factors for cognitive decline and dementia", section on 'Homocysteine'.)

A systematic review identified and analyzed 11 randomized trials studying vitamin B supplementation [173]. Four trials in 1340 individuals assessed the impact of B vitamin treatment on specific cognitive domains over a mean of 2.3 years, and seven trials in over 20,000 individuals measured global cognitive function scores (typically by Mini-Mental State Examination [MMSE]) over a mean of five years. Although B vitamin treatment lowered homocysteine concentrations by 26 to 28 percent, allocation to B vitamins versus placebo had no impact on cognitive domain scores or MMSE-type scores from baseline to the end of treatment.

Omega-3 fatty acids — The potential benefits of fish oil consumption on the risk of dementia have also been studied fairly extensively in observational studies, but the findings have been mixed [174,175]. Many longitudinal cohort studies have shown an association between higher fish oil consumption and reduced risk of dementia, cognitive decline, and/or accumulation of white matter abnormalities on brain magnetic resonance imaging (MRI) [176-182], with some exceptions [183,184]. Other studies have suggested that the benefit may vary according to apolipoprotein E (APOE) genotype, with epsilon 4 carriers deriving more benefit from fish consumption than noncarriers do [185-187].

However, randomized trials have not shown a benefit to cognitive function and have lacked power and duration to test whether consumption reduces incident dementia. A meta-analysis of three trials that studied the impact of omega-3 supplementation on cognitive performance found no effect of treatment after 6 to 40 months of supplementation [188]. Subsequent to this review, other trials have also found no benefit [14,189], including a trial in 4203 older adults at risk for macular degeneration that found no effect of fish oil supplementation and/or lutein on composite cognitive function scores over a five-year period [189].

Fish oil consumption through dietary intake of fish or omega-3 fatty acid supplementation influences several cardiovascular risk factors. This is discussed separately. (See "Fish oil: Physiologic effects and administration".)

Ginkgo biloba — Ginkgo biloba, one of the most studied herbal remedies, does not appear to provide cognitive benefits or reduce the risk of dementia. A multicenter, randomized, double-blind placebo-controlled study of ginkgo biloba in 3069 older adults (75 years or older) found that after a median six years of follow-up, treatment was not effective in reducing the incidence of AD or all-cause dementia and did not slow cognitive decline in individuals with either normal cognition or mild cognitive impairment at baseline [190,191]. Similarly, in another clinical trial of 2854 patients aged 70 years and older with memory complaints, treatment with gingko biloba was not associated with a reduced incidence of dementia after five years of treatment [192]. (See "Clinical use of ginkgo biloba".)

Other vitamins and supplements

●Multivitamins – Randomized trials of both short-term and long-term multivitamin supplementation have not shown a consistent benefit in the prevention of cognitive decline in healthy adults; some studies have detected benefits on cognitive test performance associated with multivitamin use over one-month to three-year follow-up [193,194], while the Physicians' Health Study of older (>65 years) men followed over 12 years did not [195]. These trials were not of sufficient size or duration to detect an effect on incident dementia.

●Vitamin D – There is some evidence that vitamin D deficiency is associated with cognitive impairment in older adults, although results differ. Any effect appears to be small and of uncertain clinical significance [3,6,196]. (See "Risk factors for cognitive decline and dementia", section on 'Vitamin D deficiency'.)

Recommendations regarding appropriate vitamin D intake and other aspects of the management of patients with vitamin D deficiency are discussed separately. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

●Flavonoids – In the Nurses' Health Study, dietary intake of berries high in flavonoids (eg, blueberries, strawberries) was associated with slower rates of cognitive decline [197]. Flavonoids are believed to have antioxidant and antiinflammatory actions that may contribute to a protective effect. However, isoflavone-rich soy protein supplementation did not improve cognitive outcomes after 2.5 years in a randomized trial in 350 healthy postmenopausal females [198].

INAPPROPRIATE THERAPIES — 

Some therapies have evidence of little to no benefit for dementia and may cause harm in patients.

Cholinesterase inhibitors — Low-quality evidence suggests that cholinesterase inhibitors, which have modest symptomatic benefits in some patients with established dementia, do not delay the development of dementia in patients with mild cognitive impairment. These drugs are not recommended for prevention of dementia. This topic is discussed separately. (See "Mild cognitive impairment: Prognosis and treatment", section on 'Acetylcholinesterase inhibitors'.)

Hormone therapy — Hormone therapy is not recommended for the prevention of dementia [3,6]. Although epidemiologic studies suggested that estrogen replacement might prevent dementia [199-202], data from the Women's Health Initiative (WHI) and the WHI Memory Study (WHIMS) do not support these observations and suggest that estrogen replacement does not protect against dementia and may, in fact, increase the risk [203-206]. This topic is discussed separately. (See "Estrogen and cognitive function".)

The hormone dehydroepiandrosterone (DHEA) is produced by the adrenal gland; peak production and serum concentrations occur in young adulthood and decline progressively thereafter. DHEA has been proposed to have many potential benefits in retarding diseases associated with aging, including cognitive impairment and dementia. A systematic review of three small clinical trials of DHEA concluded that the data did not support a benefit for DHEA on cognitive function [207].

NSAIDs and aspirin — There is moderate-quality evidence that nonsteroidal antiinflammatory drugs (NSAIDs) do not prevent dementia, and given potential adverse effects, they should not be used for the treatment or prevention of dementia or cognitive impairment.

A large randomized trial studied the efficacy of naproxen, celecoxib, and placebo in the prevention of Alzheimer disease (AD) in 2528 individuals >70 years old with a history of at least one family member with AD-like dementia [208]. Imperfect screening had led to the enrollment of 53 people with premorbid dementia or mild cognitive impairment. Analysis of the study population with these individuals excluded, after two years of follow-up, demonstrated that AD risk was actually increased in both active treatment groups (hazard ratio [HR] = 4.1, 3.6). Other measures of cognition were not improved and were possibly worse in the treated groups [209]. The trial was stopped early because of an increased risk of myocardial infarction in patients treated with naproxen [208]. Long-term use of certain cyclooxygenase 2 (COX-2) inhibitors has also been associated with an increased risk of cardiovascular events. (See "NSAIDs: Adverse cardiovascular effects".)

A large randomized study of 6377 participants found that older females randomly assigned to low-dose aspirin had similar rates of cognitive decline compared with the placebo-treated group after more than five years of follow-up [210]. Similarly, a five-year study of low-dose aspirin in 3350 individuals over 50 years old found no effect of treatment on cognitive test scores [211]. In a larger clinical trial of more than 19,000 people followed for 4.7 years (the Aspirin in Reducing Events in the Elderly [ASPREE] study), aspirin showed no benefit over placebo for the risk of dementia, mild cognitive impairment, or cognitive decline [212].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cognitive impairment and dementia".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Dementia (including Alzheimer disease) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Overall impact – It is uncertain whether any single intervention described in this topic is effective in delaying or preventing dementia. However, several interventions have health benefits beyond a potential benefit on cognitive health.

●Vascular risk factor modification – Epidemiologic studies offer some suggestion that multimodality vascular risk factor reduction in midlife is worthwhile, primarily for cardiovascular outcomes; these interventions may also benefit cognitive health, although data are less clear.

In particular, hypertension is associated with an increased risk of both vascular dementia and Alzheimer disease (AD), and treatment of hypertension is beneficial to reduce the risk of cerebrovascular disease and may have a preventive effect in relation to dementia. (See 'Vascular risk factor modification' above.)

●Lifestyle modification – All people, including those with risk factors for dementia, are encouraged to maintain or increase physical activity and exercise, as long as there are no contraindications.

Similarly, a healthy diet (eg, MIND or Mediterranean diet), social interaction, and moderation of alcohol intake should be encouraged. However, we recognize that these lifestyle factors remain unproven as a means of preventing dementia. (See 'Healthy lifestyle interventions' above.)

●Cognitive training – Various cognitive interventions, including memory training, the use of external memory cues, and organizational aids, have shown positive short-term effects on cognition in healthy older adults, but clinically important and long-term impacts on dementia risk are uncertain. (See 'Cognitive activities' above.)

●Interventions with no role in dementia prevention – Prospective studies and randomized, controlled trials have not shown a clear benefit from vitamins or other dietary supplements, herbal remedies, cholinesterase inhibitors, estrogen replacement therapy, or nonsteroidal antiinflammatory drugs (NSAIDs) for the prevention of dementia, and some of these interventions may cause harm. (See 'No role for dietary supplementation or herbal remedies' above and 'Inappropriate therapies' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Michael Alexander, MD, who contributed to earlier versions of this topic review.

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  186. van de Rest O, Wang Y, Barnes LL, et al. APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline. Neurology 2016; 86:2063.
  187. Yassine HN, Braskie MN, Mack WJ, et al. Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review. JAMA Neurol 2017; 74:339.
  188. Sydenham E, Dangour AD, Lim WS. Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev 2012; :CD005379.
  189. Chew EY, Clemons TE, Agrón E, et al. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. JAMA 2015; 314:791.
  190. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 2008; 300:2253.
  191. Snitz BE, O'Meara ES, Carlson MC, et al. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA 2009; 302:2663.
  192. Vellas B, Coley N, Ousset PJ, et al. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol 2012; 11:851.
  193. Grima NA, Pase MP, Macpherson H, Pipingas A. The effects of multivitamins on cognitive performance: a systematic review and meta-analysis. J Alzheimers Dis 2012; 29:561.
  194. Baker LD, Manson JE, Rapp SR, et al. Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial. Alzheimers Dement 2023; 19:1308.
  195. Grodstein F, O'Brien J, Kang JH, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med 2013; 159:806.
  196. Balion C, Griffith LE, Strifler L, et al. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 2012; 79:1397.
  197. Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol 2012; 72:135.
  198. Henderson VW, St John JA, Hodis HN, et al. Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology 2012; 78:1841.
  199. Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 1997; 48:1517.
  200. Tang MX, Jacobs D, Stern Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996; 348:429.
  201. Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998; 279:688.
  202. LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA 2001; 285:1489.
  203. Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289:2651.
  204. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2947.
  205. Espeland MA, Rapp SR, Shumaker SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2959.
  206. Schneider LS. Estrogen and dementia: insights from the Women's Health Initiative Memory Study. JAMA 2004; 291:3005.
  207. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev 2006; :CD006221.
  208. ADAPT Research Group, Lyketsos CG, Breitner JC, et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology 2007; 68:1800.
  209. ADAPT Research Group, Martin BK, Szekely C, et al. Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 2008; 65:896.
  210. Kang JH, Cook N, Manson J, et al. Low dose aspirin and cognitive function in the women's health study cognitive cohort. BMJ 2007; 334:987.
  211. Price JF, Stewart MC, Deary IJ, et al. Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial. BMJ 2008; 337:a1198.
  212. Ryan J, Storey E, Murray AM, et al. Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline. Neurology 2020; 95:e320.
Topic 5075 Version 46.0

References

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30 : Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial.

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32 : Pharmacological treatment of hypertension in people without prior cerebrovascular disease for the prevention of cognitive impairment and dementia.

33 : Blood pressure and dementia: What the SPRINT-MIND trial adds and what we still need to know.

34 : Duration of antihypertensive drug use and risk of dementia: A prospective cohort study.

35 : Relationship Between Antihypertensive Medications and Cognitive Impairment: Part I. Review of Human Studies and Clinical Trials.

36 : Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis.

37 : Effect of the treatment of Type 2 diabetes mellitus on the development of cognitive impairment and dementia.

38 : Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.

39 : Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial.

40 : Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial.

41 : Metformin, age-related cognitive decline, and brain pathology.

42 : GLP-1RA and SGLT2i Medications for Type 2 Diabetes and Alzheimer Disease and Related Dementias.

43 : Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease?

44 : Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease.

45 : Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo.

46 : Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons.

47 : Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10.

48 : Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK.

49 : Statins Inhibit Fibrillaryβ-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier.

50 : Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.

51 : Statins for the prevention of dementia.

52 : Statins and the risk of dementia.

53 : Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study.

54 : Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study.

55 : Age-varying association between statin use and incident Alzheimer's disease.

56 : Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study.

57 : Statin use and the risk of incident dementia: the Cardiovascular Health Study.

58 : APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study.

59 : Statins and cognitive function in the elderly: the Cardiovascular Health Study.

60 : Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease.

61 : Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease.

62 : Association of statin use with cognitive decline in elderly African Americans.

63 : Statins, incident Alzheimer disease, change in cognitive function, and neuropathology.

64 : Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study.

65 : Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment.

66 : MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.

67 : Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions.

68 : Death, Depression, Disability, and Dementia Associated With Self-reported Hearing Problems: A 25-Year Study.

69 : Longitudinal Relationship Between Hearing Aid Use and Cognitive Function in Older Americans.

70 : Hearing Loss, Hearing Aid Use, and Risk of Dementia in Older Adults.

71 : A pilot randomized controlled trial of hearing aids to improve mood and cognition in older adults.

72 : Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.

73 : The association of herpes zoster and influenza vaccinations with the risk of developing dementia: a population-based cohort study within the UK Clinical Practice Research Datalink.

74 : Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis.

75 : A natural experiment on the effect of herpes zoster vaccination on dementia.

76 : Herpes Zoster Vaccination and Dementia Occurrence.

77 : Physical activity, diet, and risk of Alzheimer disease.

78 : Walking and dementia in physically capable elderly men.

79 : Physical activity, including walking, and cognitive function in older women.

80 : Social resources and cognitive decline in a population of older African Americans and whites.

81 : A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults.

82 : Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease.

83 : Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older.

84 : Leisure activities and the risk of amnestic mild cognitive impairment in the elderly.

85 : The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study.

86 : Physical fitness and lifetime cognitive change.

87 : Relation of cognitive activity to risk of developing Alzheimer disease.

88 : Physical activity and dementia risk in the elderly: findings from a prospective Italian study.

89 : Cardiorespiratory fitness and brain atrophy in early Alzheimer disease.

90 : Leisure activities and the risk of dementia in the elderly: results from the Three-City Study.

91 : Physical activity and cognition in women with vascular conditions.

92 : Activity energy expenditure and incident cognitive impairment in older adults.

93 : Total daily physical activity and the risk of AD and cognitive decline in older adults.

94 : Influence of late-life cognitive activity on cognitive health.

95 : Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis and Disability) study.

96 : Exercise and Alzheimer's disease biomarkers in cognitively normal older adults.

97 : Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia.

98 : Association Between Mentally Stimulating Activities in Late Life and the Outcome of Incident Mild Cognitive Impairment, With an Analysis of the APOEε4 Genotype.

99 : An active and socially integrated lifestyle in late life might protect against dementia.

100 : Cognitive and physical activity and dementia: A 44-year longitudinal population study of women.

101 : The A4 study: stopping AD before symptoms begin?

102 : Aerobic exercise to improve cognitive function in older people without known cognitive impairment.

103 : The impact of exercise on the cognitive functioning of healthy older adults: a systematic review and meta-analysis.

104 : Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials.

105 : Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review.

106 : Association of cardiorespiratory fitness with dementia risk across different levels of genetic predisposition: a large community-based longitudinal study.

107 : Longitudinal effects of exercise according to the World Health Organization guidelines on cognitive function in middle-aged and older adults.

108 : Does cardiorespiratory fitness mediate or moderate the association between mid-life physical activity frequency and cognitive function? findings from the 1958 British birth cohort study.

109 : Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial.

110 : Effect of a long-term intensive lifestyle intervention on prevalence of cognitive impairment.

111 : The association between midlife cardiorespiratory fitness levels and later-life dementia: a cohort study.

112 : Cardiorespiratory fitness and risk of dementia: a prospective population-based cohort study.

113 : Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study.

114 : Social Isolation and Cognitive Function in Later Life: A Systematic Review and Meta-Analysis.

115 : Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.

116 : The impact of social activities, social networks, social support and social relationships on the cognitive functioning of healthy older adults: a systematic review.

117 : Association of social contact with dementia and cognition: 28-year follow-up of the Whitehall II cohort study.

118 : Associations between social networks, cognitive function, and quality of life among older adults in long-term care.

119 : Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials.

120 : Primary prevention of cardiovascular disease with a Mediterranean diet.

121 : The Mediterranean diet, its components, and cardiovascular disease.

122 : Mediterranean diet and risk for Alzheimer's disease.

123 : The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease.

124 : Mediterranean diet and mild cognitive impairment.

125 : Adherence to a Mediterranean diet, cognitive decline, and risk of dementia.

126 : Food combination and Alzheimer disease risk: a protective diet.

127 : Mediterranean diet, stroke, cognitive impairment, and depression: A meta-analysis.

128 : Association between Mediterranean diet and dementia and Alzheimer disease: a systematic review with meta-analysis.

129 : MIND diet associated with reduced incidence of Alzheimer's disease.

130 : Association of the Mediterranean Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet With the Risk of Dementia.

131 : Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons.

132 : Cognitive rehabilitation in the elderly: a randomized trial to evaluate a new protocol.

133 : Improving memory, knowledge, satisfaction, and functioning via an education and intervention program for older adults

134 : Long-term effects of cognitive training on everyday functional outcomes in older adults.

135 : Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review.

136 : Speed of processing training results in lower risk of dementia.

137 : The effects of the ACTIVE cognitive training trial on clinically relevant declines in health-related quality of life.

138 : The effect of speed-of-processing training on depressive symptoms in ACTIVE.

139 : Episodic memory training in elderly: A systematic review.

140 : Effectiveness of Cognitive Interventions in Older Adults: A Review.

141 : Influence of education and occupation on the incidence of Alzheimer's disease.

142 : Education and other measures of socioeconomic status and risk of incident Alzheimer disease in a defined population of older persons.

143 : Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study.

144 : Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline.

145 : Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis.

146 : Education and dementia: what lies behind the association?

147 : Brain volume decline in aging: evidence for a relation between socioeconomic status, preclinical Alzheimer disease, and reserve.

148 : Cognition, reserve, and amyloid deposition in normal aging.

149 : Association of lifetime intellectual enrichment with cognitive decline in the older population.

150 : Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial.

151 : Education and the course of cognitive decline in Alzheimer disease.

152 : Education delays accelerated decline on a memory test in persons who develop dementia.

153 : Does cognitive reserve shape cognitive decline?

154 : Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

155 : Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

156 : Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease.

157 : Association of vitamin E and C supplement use with cognitive function and dementia in elderly men.

158 : Intake of flavonoids and risk of dementia.

159 : Dietary intake of antioxidants and risk of Alzheimer disease.

160 : Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study.

161 : Dietary intake of antioxidants and risk of Alzheimer disease: food for thought.

162 : Antioxidant vitamin intake and risk of Alzheimer disease.

163 : Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.

164 : Serum alpha-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairment.

165 : Dietary antioxidants and long-term risk of dementia.

166 : Impact of antioxidants, zinc, and copper on cognition in the elderly: a randomized, controlled trial.

167 : Vitamin E and donepezil for the treatment of mild cognitive impairment.

168 : A randomized trial of vitamin E supplementation and cognitive function in women.

169 : Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women's Antioxidant and Cardiovascular Study.

170 : Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE).

171 : A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians' Health Study II.

172 : Vitamin B-Can it prevent cognitive decline? A systematic review and meta-analysis.

173 : Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals.

174 : Omega-3 fatty acids intake and risks of dementia and Alzheimer's disease: a meta-analysis.

175 : Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies.

176 : Dietary intake of fatty acids and fish in relation to cognitive performance at middle age.

177 : Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease.

178 : Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.

179 : Fish consumption and cognitive decline with age in a large community study.

180 : Dietary patterns and risk of dementia: the Three-City cohort study.

181 : Fish consumption and risk of subclinical brain abnormalities on MRI in older adults.

182 : The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers.

183 : Diet and risk of dementia: Does fat matter?: The Rotterdam Study.

184 : Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk.

185 : Association of Seafood Consumption, Brain Mercury Level, and APOEε4 Status With Brain Neuropathology in Older Adults.

186 : APOEε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline.

187 : Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein Eε4 Carriers: A Review.

188 : Omega 3 fatty acid for the prevention of cognitive decline and dementia.

189 : Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial.

190 : Ginkgo biloba for prevention of dementia: a randomized controlled trial.

191 : Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial.

192 : Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

193 : The effects of multivitamins on cognitive performance: a systematic review and meta-analysis.

194 : Effects of cocoa extract and a multivitamin on cognitive function: A randomized clinical trial.

195 : Long-term multivitamin supplementation and cognitive function in men: a randomized trial.

196 : Vitamin D, cognition, and dementia: a systematic review and meta-analysis.

197 : Dietary intakes of berries and flavonoids in relation to cognitive decline.

198 : Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial.

199 : A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging.

200 : Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease.

201 : Estrogen therapy in postmenopausal women: effects on cognitive function and dementia.

202 : Hormone replacement therapy and cognition: systematic review and meta-analysis.

203 : Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

204 : Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study.

205 : Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.

206 : Estrogen and dementia: insights from the Women's Health Initiative Memory Study.

207 : Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people.

208 : Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial.

209 : Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib.

210 : Low dose aspirin and cognitive function in the women's health study cognitive cohort.

211 : Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial.

212 : Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline.

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