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Research overview
Systematic review

Primary and secondary prevention interventions for cognitive decline and dementia

Dementia is a syndrome characterised by deterioration in memory, thinking, behaviour, and the ability to perform everyday activities, which ultimately may lead to total dependence and death. Since the world’s population is steadily growing older, the number of people with dementia is also increasing. It is therefore of utmost importance to identify effective strategies to prevent or delay its onset.

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  • Issued/Revised: September 2016
  • By: Folkehelseinstituttet
  • Flodgren GM, Berg RC. Primary and secondary prevention interventions for cognitive decline and dementia, Folkehelseinstituttet. Research overview September 2016. ISBN (digital): 978-82-8082-745-6. Available at www.fhi.no/en

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Dementia is a syndrome characterised by deterioration in memory, thinking, behaviour, and the ability to perform everyday activities, which ultimately may lead to total dependence and death. Since the world’s population is steadily growing older, the number of people with dementia is also increasing. It is therefore of utmost importance to identify effective strategies to prevent or delay its onset.

The key findings of this overview of reviews are based on evidence from eight systematic reviews. The results for the single interventions targeting cognitively healthy people suggest that compared to control:

  • Antihypertensive drugs may lead to a slight decrease in incidence of dementia in people with hypertension (low certainty of evidence).
  • Statin therapy probably leads to little or no difference on incidence of dementia in people with, or at risk of, cardiovascular disease (moderate certainty).
  • Omega-3 Fatty Acids (FAs) probably lead to little or no effect on cognitive test scores (moderate to high certainty).
  • Computerised cognitive training probably leads to a slight improvement in cognitive test scores directly after the training (moderate certainty).
  • Aerobic exercise may lead to little or no effect on cognitive test scores (low certainty).

The results for the interventions targeting people with mild cognitive impairment suggest that compared to control:

  • Cholinesterase inhibitors probably lead to a slight decrease in dementia incidence, but  to significantly more adverse events (moderate certainty).
  • Vitamin E probably leads to little or no difference in incidence of Alzheimer’s dementia (moderate certainty).
  • Omega-3 FAs probably lead to little or no difference in cognitive test scores (moderate to high certainty).

We did not find any reviews that evaluated the effects of interventions targeting more than one risk factor, and we can therefore not say anything about the combined effects of these interventions.

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Background

Dementia is a chronic syndrome characterised by deterioration in memory, thinking, behaviour, and the ability to perform everyday activities, which often leads to total dependence and death. The world’s population is steadily growing older, and as dementia is more prevalent in people over 70, and increases with increasing age, the number of people with dementia is also increasing. In 2012, around 71, 000 people in Norway had a dementia diagnosis, which represents 1.6% of the total population.

Objectives

The aim of this overview of reviews was to answer the following two questions: 1) What is the documented effectiveness of interventions to prevent cognitive decline or incidence of dementia in cognitively healthy people (primary prevention), 2) What is the documented effectiveness of interventions to prevent (further) cognitive decline or progression to dementia in people with mild cognitive impairment (MCI) or other early symptoms or signs of dementia (secondary prevention)?

Methods

We conducted an overview of reviews in accordance with the Knowledge Centre’s handbook. We searched in eight databases up to February 2016 for reviews evaluating the effects of interventions to prevent or delay cognitive decline or dementia in people with or without MCI. Two people independently screened all titles and abstracts, reviewed full texts, assessed review quality, and graded the certainty of the evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool. One author extracted data, and another checked that it was correct.

Results

We included eight high quality reviews published between 2009 and 2016. Five of the reviews involved primary prevention interventions for cognitively healthy people. Three reviews included secondary prevention interventions for people with MCI or memory complaints. The reviews evaluated the effects of pharmacological therapies (3 reviews), dietary supplements (3 reviews), aerobic training (one review), and cognitive training (one review). The comparator in the latter two was either another active intervention or no intervention, and placebo in all the others.

Primary prevention interventions

Pharmacological therapies

Antihypertensive drugs. We included one review (4 trials; n=15,936) concerned with the effects of antihypertensive drugs on dementia incidence in older people with hypertension. The participants were recruited in Europe, North America, China, Australasia and Tunisia. The pooled result (Odds Ratio [OR]: 0.89 [0.74 to 1.07]) indicates that antihypertensive drugs may lead to a slight decrease in incidence of dementia, as compared to placebo, at 1.8 to 4.5 years follow up.

Cholesterol lowering drugs (Statins). We included one review (2 trials; n=26,340) concerned with the effects of statins on incidence of dementia in cognitively healthy older people with evidence of, or at high risk of, cerebrovascular disease. The studies were conducted in the UK, Ireland, and the Netherlands. The result of one trial (OR: 1.00 [0.61 to 1.65], n=20,536) indicates that statin therapy may lead to little or no difference in incidence of dementia, as compared to placebo. The other trial (n= 5,804) reported no difference in cognitive test scores between groups at mean 3.2 years follow up.

Dietary supplements

Omega-3 Fatty Acids (FAs). We included one review (3 trials; n= 4,080) which evaluated the effects of Omega-3 FAs on cognitive decline in cognitively healthy participants. The pooled results (Standardised Mean Difference [SMD] [4 tests]: 0.06 higher to 0.04 lower scores; Mean Difference [MD] [2 tests]: 0.12 higher to 0.07 lower scores) suggest that Omega-3 FA supplementation probably leads to little or no difference in overall cognitive function, as compared to placebo, at 6 to 40 months follow up.

Aerobic exercise

We included one review (12 trials; n= 754) which evaluated the effects of supervised aerobic exercise on cognitive function in cognitively healthy older people. The studies were conducted in the USA, Canada and France. The pooled results suggest that aerobic exercise may lead to little or no effect on cognitive test scores (SMD: range 0.09 lower to 0.30 higher scores; MD [2 tests]:0.10 to 0.16as compared to no intervention at 8 to 24 weeks follow up).

Cognitive training

We included one review (52 trials; n=4,885) which evaluated the effects of computerised cognitive training (CCT) on cognitive decline in cognitively healthy people. The participants were from the USA, Europe, Canada, Australia, Israel, China, Taiwan, South Korea, and Japan. The pooled result of this review (Hedge’s g: 0.22 [0.15 to 0.29]) suggests that CCT probably leads to a small improvement in cognitive test scores directly after the training.

Secondary prevention interventions

Pharmacological therapies

Cholinesterase inhibitors. We included one review (9 trials; n=5,149) concerned with the effects of cholinesterase inhibitors for the prevention of dementia in people with MCI. The studies were conducted in USA, Canada, Singapore, and Germany. The pooled results suggest that cholinesterase inhibitors may lead to a slight decrease in progression to dementia (Relative Risk [RR]: 0.84 [0.70 to 1.02]), at 3 years, but to more adverse events than placebo (RR: 1.09 [1.02 to 1.16]).

Dietary supplements

Vitamin E. We included one review (1 trial; n=769) of the effects of vitamin E on dementia incidence in people with MCI. The results of this single trial, conducted in USA and Canada, suggest that Vitamin E supplementation possible has little effect on incidence of AD (Hazard Ratio: 1.02 [0.74 to 1.41]) at 36 months, as compared to placebo.

Omega-3 FAs. We included one review (4 trials; n= 676) of the effects of Omega-3 FAs on cognitive decline in people with MCI. The studies were conducted in the Netherlands, England, Wales, Japan, Israel, and the USA. The pooled results show that Omega-3 FAs probably lead to little or no difference in cognitive function (MD: 0.16 higher to 0.05 lower scores) at median 14.5 to 24 weeks, as compared to placebo.

Discussion

We included eight high quality reviews (86 original studies) concerned with the effects of interventions aimed at preventing cognitive decline and dementia. Results from four of these reviews suggest that statin therapy, Omega-3 FAs and vitamin E supplements probably lead to little or no difference in cognitive function or incidence of dementia. The results for cholinesterase inhibitors and antihypertensive drugs, suggest that these drugs may lead to a slight decrease in incidence of dementia, but that cholinesterase inhibitors probably lead to more adverse events than placebo. CCT probably leads to slightly improved cognitive function directly after the training, while aerobic exercise may lead to little or no difference in cognitive function.

We did not identify any eligible high quality reviews concerned with the effects of healthy life styles (other than aerobic exercise), e.g. change to a healthy diet, decreased alcohol use, etc., or other risk factors, e.g. depression, lack of social engagement, or low educational attainment. We found no reviews assessing the effects of interventions targeting multiple risk factors to prevent cognitive decline or dementia.

We unfortunately still have little knowledge from systematic reviews of effective preventive interventions, addressing single or multiple risk factors for dementia.

Conclusions

We found no convincing evidence for the effectiveness of the interventions included in this overview of reviews in preventing cognitive decline or dementia. Wide confidence intervals and few events in some of the analyses warrant caution when interpreting the results. As progression to dementia is partly determined by a number of modifiable factors related to lifestyle, environment, depression, educational level, and degree of social interaction, it is possible that preventive interventions may be more effective if they take into account the multifaceted aetiology behind the disease, i.e. interventions that targets multiple risk factors.