Obesity and high body mass index

Previous studies have shown risk factors associated with coronary disease, stroke, or other vascular disease also predict dementia. The research outcomes from a number of studies confirm an association between obesity in middle age and future risk of dementia.

Two longitudinal population-based studies support the link between mid-life obesity and later life dementia. One study analysed health data from 10 276 men and women who were aged between 40–45 when they underwent detailed health evaluations during the period of 1964 to 1973.⁶ Upon re-evaluation in later life, it was found that the mid-life weight–dementia risk link appeared to be linear, with obese individuals (those with a Body Mass Index [BMI] calculation >30), having a 74% increased risk of dementia and overweight individuals (with a BMI range of 25–29) having a 35% greater dementia risk in comparison to individuals who were within the normal BMI range. Another study followed a sample of 7402 men who were aged between 47–55 when they attended medical exams during 1970–1973. They underwent a follow-up exam in 1998 and these results displayed a similar pattern to the previous research after controlling for smoking, socioeconomic status, blood pressure, diabetes and serum cholesterol.⁷ They found that those individuals with higher BMI (22.50–24.99) had a substantially increased dementia risk than those who had low to normal BMI (20.00–22.49) at mid-life. The results from these studies suggest that obesity in mid-life may pose a substantial risk for developing dementia in later life above and beyond other risk factors (such as smoking and cholesterol).

Interestingly, the results of an American cardiovascular health study yielded different results.⁸ While this study also measured the link between mid-life weight and dementia, it also compared obesity in late-life with dementia. While the 2798 participants initially evaluated were found to be free from dementia in mid-life, they observed, in line with other studies, that those who were overweight or obese initially had a higher risk of developing dementia in later life. However, the study prospectively followed participants for a follow-up evaluation and found that in later life, a BMI within the normal range was associated with a higher risk of dementia, while a higher BMI was unrelated to increased dementia risk. The authors concluded that this reverse effect in later life was a reflection of the physical changes that occur in demented individuals as they approach a disabled status. This finding is supported by other studies which show that higher baseline BMI and slower declining BMI during later life is associated with a reduced risk of dementia.⁹

Alcohol intake

A longitudinal study of an elderly community sample free of dementia at baseline looked at cognitive functions and self-reported drinking habits. Drinking habits were assessed every 2 years and were followed for an average of 7 years.¹⁰ Cognitive measures were compared across 3 groups categorised using self-reported drinking habits. The groups compared were: no drinking, minimal drinking and moderate drinking. Interestingly they observed that mild to moderate drinking was associated with lesser declines in learning and memory tests compared with those who abstained from alcohol completely. This relationship was found to be more pronounced when comparing those who had always consumed alcohol or those who no longer drank alcohol to those who had abstained from alcohol consumption over a lifetime.¹⁰

A recent systematic review and meta-analysis of 23 studies (mainly epidemiological in nature) also concluded that small amounts of alcohol in earlier adult life may be protective against developing dementia (risk ratio [RR] 0.63; 95% CI 0.53–0.75) and Alzheimer’s disease (RR 0.57; 0.44–0.74) later in life, and less for vascular dementia (RR 0.82; 0.50–1.35) or cognitive decline (RR 0.89; 0.67–1.17).¹¹

Smoking

Researchers from The Netherlands studied the effect of smoking on cognitive decline over a 5-year period at middle age (43–70 years). They found that among smokers, as numbers of cigarettes smoked and number of years spent smoking increased, functioning in a number of cognitive indices declined.¹² Another study found that having stiff lungs, which impairs an individual’s ability to blow out a large volume of air quickly, was associated with increased risk of dementia.¹³ Additionally, a recent stratified random sample study of non-smokers found a relationship between exposure to second-hand smoke and cognitive decline.¹⁴

Heavy metal exposure

Metal exposure is of interest to researchers as a possible risk factor for dementia given that in AD accumulation of metals within the brain form characteristic amyloid plaques, a key pathological trait in the disorder. Additionally, studies have observed that certain metals, such as copper, aluminium and zinc have been implicated in the precipitation and cytotoxicity of amyloid protein.²³ One recent study has found evidence that high exposure to aluminium in drinking water was significantly associated with increased dementia risk,²⁴ and this finding has been replicated in a number of epidemiological studies.²⁵

Education

Research has found that attaining a higher education is an independent protective factor for dementia and cognitive decline, however this has been debated.²⁶ On the other hand, studies investigating later-life cognitive stimulation practices for individuals who were already demented improved some cognitive domains as well as the individual’s quality of life when compared to individuals who received their regular treatment in the absence of cognitive stimulation.²⁷ This result has been mirrored in prospective studies within non-clinical populations, where older individuals (75 years +) with increased cognitive activity during their leisure activities show reduced risk of developing mild cognitive impairment.²⁸

Work complexity

A case-control study, controlling for age, gender, and level of education found that the more complex the work (either with people or with data) was associated with reduced risk of AD.²⁹ The study included 10 079 members of the population-based Swedish Twin Registry who were participants in the HARMONY study. They analysed data with case-control and co-twin control designs. The co-twin control design provides control over genetic and familial factors.

Loneliness and socialisation

Social isolation in old age has been associated with the risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. A longitudinal clinicopathologic cohort study found that the lonely persons had almost twice the risk of developing dementia compared with those who were not classified as lonely.³⁰ This effect remained apparent even after controlling for social isolation. This study observed that more lonely people showed lower indices of cognitive function at baseline and increased rapid cognitive decline at follow-up.

Pets

A recent review summarised 9 studies that investigated dog therapy for older people with dementia residing within residential aged care.³¹ The most common findings were substantial decreases in agitated episodes and increased socialisation during dog contact. Interestingly, the improvements seen in social behaviour were unrelated to dementia severity. Additionally, improvements on various measures of overall function were also observed in those receiving dog therapy.

Personality

Personality testing found Japanese centenarians have optimistic attitudes, adaptability, and an easy-going approach to life.³² Strong social integration and a deep spirituality were particularly evident among older women when in their prime of life. They scored low when it came to feelings of ‘time urgency’ and ‘tension’ and high in ‘self-confidence’ and ‘unyieldingness.’

In another study, investigators linked high neuroticism, a personality trait, to dementia.³³ They assessed the personality traits among 506 dementia-free individuals participating as part of the Kungsholmen Project (Sweden) and prospectively followed them for 6 years on average. The main trends observed were for participants scoring lowest in trait neuroticism and combined with high trait extraversion were associated with reduced risk of dementia. Additionally, it was also observed that in individuals who were socially isolated, even low neuroticism alone was associated with decreased dementia risk.

Diet

Mediterranean diet

There is converging evidence that composite dietary patterns such as the Mediterranean diet are related to lower risk for cardiovascular disease, several forms of cancer, and overall mortality. The Mediterranean diet is generally comprised of a high intake of fruit, vegetables, legumes and grains, preferring fish to red meat, mainly cooking with olive oil and the consumption of a moderate amount of red wine.⁴⁰ A recent review concluded that essential components of the Mediterranean diet, including poly-unsaturated fatty acids (PUFA’s), cereals and wine, seem to be protective against cognitive decline.⁴¹ A study prospectively evaluated 2258 community-based non-demented individuals in New York every 1.5 years, and found that higher adherence to the Mediterranean diet is associated with a reduction in risk for AD.⁴² A multiethnic community study using Cox proportional hazards method found that higher adherence to the Mediterranean diet is associated with a trend for reduced risk of developing MCI and with reduced risk of MCI conversion to AD.⁴³

Okinawa diet

Observing inhabitants of the Japanese island, Okinawa, they generally have a long life expectancy and demonstrate low prevalence of dementia. Outside of genetic factors, lifestyle appears to be a main contributor for longevity. Okinawan’s consume more nutrient-dense, calorie-starved foods such as soy, fruits, vegetables, wholegrains, sprouts, broth-based soups, seaweed, sweet potatoes, fish, beans, and yogurt, and infrequent consumption of breads, cheese, oil, nuts, meats and sweets. Other features of Okinawan’s include eating small frequent meals (till 80% full), drinking water, green and/or black tea, plenty of exercise through physical labour, martial arts, dance and maintaining a strong community bond that uplifts the spirit.³³

Green tea

In analysis of cross-sectional data from a community-based Comprehensive Geriatric Assessment, Japanese researchers examined the association between green tea consumption and cognitive function in humans.⁴⁴ The assessment comprised 1003 individuals aged 70 years or older, who answered self-report questions about the frequency of green tea consumption. The participants had their cognitive function evaluated, scored using the Mini-Mental State Examination (MMSE). The research observed that the higher consumption of green tea, the lower the prevalence of cognitive impairment. Interestingly, the findings for green tea were highly statistically significant whereas a similar analysis for black or oolong tea and coffee was not statistically significant. Currently, however, there is a lack of substantial clinical trials or long-term prospective design studies, which need to be carried out in order to make any definitive claims for green tea.

Caffeine

Caffeine is a drug which is very widely consumed, in the Western world. Previous experimental models have demonstrated some neuroprotective effects of caffeine at low doses when administered chronically.⁴⁵ Subsequent research has investigated the association between caffeine consumption in midlife and AD in late life, with mixed results. One study reported mid-life caffeine consumption to be inversely related to AD while controlling for other variables.^{46, 47} In a more recent study, the lowest risk of Alzheimer’s disease was found in individuals who consumed on average 3–5 cups of coffee per day in midlife.⁴⁶ A prospective study into the effects of caffeine consumption over a 2 and 4 year follow-up found that only in women was high daily consumption of caffeine associated with reduced cognitive decline in some measures.⁴⁸ The research surrounding caffeine as a possible preventative for later life dementia is lacking and requires larger, long-term studies before any definitive claims can be made.

Meditation

Meditation practices have various health benefits including the possibility of preserving cognition and preventing dementia. While the exact mechanisms remain investigational, there is some evidence from a few cognitive, brain electrical (EEG), and structural neuro-imaging studies. In 1 cross-sectional study, meditation practitioners were found to have a lower age-related decline in the thickness of specific cortical regions.⁵⁵ They found that, compared to non-mediators of the same age, the differences in cortical thickness were most pronounced in the older participants, suggesting that meditation may have contributed to offsetting age-related cortical thinning. Additionally, the thickness of 2 cortical regions correlated with meditation experience.

Cognitive behavioural therapy (CBT)

Anxiety is a common symptom in dementia, often contributing to limited independence and a greater need to be placed in nursing home care. One study assessed CBT as a means to treat dementia related anxiety, comparing the results from 2 patients who were treated with a dementia-specific modified version of CBT.⁵⁶ The researchers made modifications in the content, structure, and learning strategies of CBT in the treatment process, with the patients receiving education and awareness training and were taught the skills of diaphragmatic breathing, coping self-statements, exposure, and behavioural activation. They found improvements in anxiety as measured by standardised rating scales. CBT has also been shown to be beneficial in treating anxiety in the caregivers and family members of dementia sufferers.^{57, 58}

Additionally, positive belief-based CBT has been used for teaching mnemonic strategies to older adults who were still in the early stages of dementia as a means to improve cognitive function. A 7-week group intervention study used CBT to address unhelpful memory-related beliefs in 3 older men with mild/moderate dementia and associated low mood or anxiety.⁵⁹ While results were promising, the researchers concluded that further research into the use of CBT is required.

Music and relaxation therapy

Relaxation can help lower the levels of agitation and stress in AD patients and their caregivers. Simple techniques such as massage, therapeutic and physical touching can help keep patients calm by allaying anxiety. A review of the literature of 8 research-based articles, found that demented older individuals who listened to their preferred music during the study intervention period had positive results, one of which was the reduction of some agitated behaviours.⁶⁰ The review cautioned that while only the findings in 1 study did not reach statistical significance, the sample numbers were small and further investigation was necessary.

Aromatherapy

Aromatherapy is the use of pure essential oils from fragrant plants to help relieve health problems and improve the quality of life in general. Aggressiveness, restlessness and excitability are experienced by a large proportion of people with severe dementia, and can be distressing for patients and caregivers. Aromatherapy may play a role in helping to alleviate these symptoms.

One study of 72 people living in long-term care facilities in the UK were randomly assigned to aromatherapy (essential lemon balm oil) or placebo (sunflower oil), combined with a base lotion.⁶¹ Caregivers applied the oils onto the patients’ faces and arms twice a day. Over 4 weeks of treatment, the aromatherapy treatment group resulted in a 35% improvement in agitation compared to 11% with placebo treatment. Also, scores on quality of life indices also significantly improved. The lemon balm appeared to be well tolerated and safe with no serious adverse side-effects.

A Cochrane review identified 3 randomised control trials (RCTs) of aromatherapy for dementia, however, found several methodological difficulties with 2 of the studies. The review concluded ‘a statistically significant treatment effect in favour of the aroma therapy intervention on measures of agitation and neuropsychiatric symptoms’ in 1 of the trials.⁶² More research is required.

Brain training

A recent Cochrane review investigated whether cognitive training and cognitive rehabilitation improved symptomatology within individuals with dementia.⁶³ The review concluded that no definite protective effects were observed and the authors argued that more studies of a larger power and of a better methodological design were required before concluding the efficacy of such training.

There have also been a number of studies evaluating the efficacy of brain training on cognitive processes and activities of daily living in older, cognitively healthy participants. Overall, the findings have been positive, with a number of studies investigating large cohorts in controlled clinical trials. In a study of 2832 persons living in 6 US cities, 10 sessions of computerised cognitive training were used that included specific cognitive domains such as episodic memory and reasoning.⁶⁴ Each intervention improved the targeted cognitive ability compared with baseline. In addition, booster training improved specific cognitive functions that were sustained at a 2-year follow-up. Improvements due to training were of the same magnitude as the amount of age-associated decline expected over a 7–14 year period in individuals without dementia. In a follow-up study, brain training was shown to improve trained cognitive abilities and this was maintained after 5 years.⁶⁵ The intervention included 10 sessions of training and then follow-up booster training at 11 and 35 months. Importantly, brain training also resulted in a reduced functional decline in activities of daily living over this time.

Two other recent studies have also shown benefits associated with cognitive training. In 1 of these studies a cohort of 487 participants used a cognitive training battery and showed improvements in memory and attention after 8 weeks (1 hour per day, 5 days per week).⁶⁶ In the other study, improvements were found both in the cognitive domains being trained and also in non-related standardised neuropsychological tasks.⁶⁷ The authors concluded that ‘intensive plasticity-engaging training can result in an enhancement of cognitive function in normal mature adults’.

There is also evidence of neurobiological changes that occur as a result of brain training suggesting possible neural underpinnings associated with brain training studies outlined above. In a neuro-imaging study, the density of Dopamine D1 receptors were assessed before and after 14 hours (5 weeks) of working memory training.⁶⁸ There were significant changes in D1 binding potential in both prefrontal and parietal brain regions ‘demonstrating a reciprocal interplay between mental activity and brain biochemistry in vivo’.

Insomnia

Insomnia is a common problem in AD. In a randomised-control trial of 36 community dwelling patients with AD and suffering sleep problems, 17 were randomised into active treatment with their caregivers receiving specific treatment about setting up a sleep hygiene program and training in behaviour management skills.⁶⁹ They were also instructed to walk daily and to increase daytime light exposure with the use of a light box. Control subjects (n = 19) received general dementia education and caregiver support. The active group demonstrated a significant (p<.05) reduction in the number of night-time awakenings, total time awake at night, and depression. These benefits persisted at 6-month follow-up.

Light therapy

Light therapy may be beneficial in improving some cognitive and non-cognitive symptoms of dementia. A 2008 study showed that light therapy reduced cognitive decline and ameliorated depressive symptoms in individuals with dementia.⁷⁴ Moreover, in the same study mood was adversely affected with administration of melatonin, often administered to improve insomnia. The authors recommended that melotonin should only be taken in combination with light therapy. Their results suggested that the bright light therapy did demonstrate an improvement in some cognitive domains, especially in the participants who were in the initial stages of AD. Their results suggested that bright light therapy improved cognitive functions, especially in individuals who were in early stages of AD.⁷⁵ However, a 2004 Cochrane review found that there was insufficient evidence to suggest that light therapy is effective in managing sleep, behaviour, cognitive, or mood disturbances associated with dementia.⁷⁶ The authors found only 3 studies that fulfilled all inclusion criteria and recommended that more properly constructed studies are necessary to draw solid conclusions.

Exercise

The relationship between physical exercise and cognition in older individuals has been investigated in a number of studies. One study showed that either memory-based cognitive exercises or cardiovascular exercises resulted in older individuals out-performing age-matched participants in tests of memory functioning.⁷⁷ Additionally, the implementation of a 24-week physical activity program in adults who believed they had a memory impairment (but were dementia free) found adequate improvements in memory, even after an 18 month follow-up period.⁷⁸ Another recent study found that dementia-free elderly individuals significantly improved in fluid intelligence measures after participation in 2 x 1 hour general exercise classes (conducted over a period of 6 months), compared to a no-exercise control group or a group who participated in a flexibility based relaxation class.⁷⁹ Recent Cochrane reviews, however, indicated that the bank of research into the effects of exercise and dementia are still inconclusive due to insufficient research methods.⁸⁰

Tai chi

A study compared healthy individuals aged 45–74 years from Fuyang city, 53 of whom practiced tai chi exercise for half a year or more, and 48 were ‘no exercise’ controls.⁸¹ The participants were compared across 3 age groups: 45–54 years, 55–64 years, and 65–74 years. Additionally, the tai chi group was subdivided into 3 groups according to experience in tai chi: ≤3 years, 4–6 years, and ≥7years. The cognitive function of both tai chi experienced and no exercise control groups declined with age, but this decline was slower in the tai chi group. In addition, people who had practiced tai chi for a longer duration had less cognitive decline than those with less experience. The researchers concluded that long-term tai chi exercise can possibly benefit cognitive function in middle-aged and old people.

A recent study examined performance on cognitive and physical tasks in 20 older adult subjects after participation in a 10-week tai chi program.⁸² They found that compared to baseline, 2 measures of executive cognition had improved. Collectively these studies suggest some beneficial effects of tai chi for cognition in older adults; however, more controlled randomised trials are required for conclusive evidence.

Diet

A high dietary intake of fruit, vegetables, legumes, wholegrains, fish and olive oil is protective of cognition and towards reducing the risk of dementia (refer to risk factor section above, under diet). Therefore, encouraging a Mediterranean diet may play a role in helping to reduce any further deterioration of cognition and memory in patients with established dementia and Alzheimer’s disease.^40–43

Vitamins B6, B12 and folate

The majority of conclusions drawn for the importance of substantial B vitamin status, including folic acid, are derived from studies finding that compromised brain functioning is linked to vitamin deficiencies.⁸³ In the normal elderly population, vitamin deficiency is quite common, leading to the suggestion that B vitamin status is related to cognitive performance or possibly dementia, however, current findings do not paint a clear picture. One study postulates the link between B vitamin deficiency and impairment of methylation reactions leading to the damage of brain tissue.⁸³ Another theory that relates to B vitamin deficiency postulates that elevated homocysteine levels are responsible for cognitive dysfunction given that elevated homocysteine has been linked to vascular disease, dementia and AD. One recent randomised placebo-controlled trial aimed to determine the effects of folic acid, vitamin B12, riboflavin, and vitamin B6 supplementation on homocysteine levels and cognitive function.⁸⁴ The trial was comprised of 185 patients who suffered ischaemic vascular diseases and were aged 65 years or more. After 1 year, homocysteine levels were lower in the group receiving a combination of folic acid and B12 than patients not receiving the treatment. However, this folic acid/vitamin B12 combined treatment did not significantly alter cognitive performance; neither did a riboflavin/vitamin B6 combined treatment. However, a separate more recent cross-sectional study in the Japanese elderly population reported an independent positive association between reduced folate and vitamin B12 levels and cognitive decline.⁸⁵

This prospective 5-year study measured markers of vitamin B12 status and brain volume loss in older individuals (aged 61–87 years). They found that individuals with lower B12 vitamin status displayed greater decreases in brain loss and the relationship remained significant after controlling for ‘age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE 4 status, homocysteine and folate’.⁸⁵ Another study revealed that elderly individuals with a pre-existing vitamin B12 deficiency and mild to moderate dementia did show an improvement in cognitive function with B12 supplementation, however those with advanced dementia displayed an improvement in neurological symptoms only.⁸⁶

A cross-sectional and longitudinal analysis published in the American Journal of Medicine in 2005 in a cohort of 499, 70–79 year olds, demonstrated those with elevated homocysteine levels or low levels of folate or vitamin B6, demonstrated worse baseline cognitive function.⁸⁷ After adjusting for variables, those with bottom quartile folate levels had a 1.6 fold increased risk of being in the worst quartile of 7-year cognitive decline. Reduced folate levels appear to be a greater risk factor for cognitive decline. Chan et al.⁸⁸ examined the efficacy of a vitamin/nutraceutical formulation in a 12-month pilot trial in individuals with early-stage Alzheimer’s disease. The formulation contained a mixture of folate, vitamin B6, vitamin E, s-adenosyl methionine, N-acetyl cysteine and acetyl-L-carnitine. Those taking the formulation performed better on neuropsychiatric and daily living measures than the individuals who were taking pharmacological medications or placebo. While a larger clinical trial is required to confirm these preliminary findings, generally previous large cross section studies have found a trend between adequate folate intake (at or above the RDI) and reduced risk of AD.^{89, 90} A similar result was found by Wouters-Wesseling et al. (2005)⁹⁰ who administered a vitamin-nutrient enriched drink to elderly individuals in their double-blind, randomised, placebo-controlled study. The 67 participants received either the drink or placebo for 6 months. They found significant differences after 6 months in a word learning test, and a category fluency test compared to the placebo group. Additionally, they observed that vitamin B12 levels significantly increased and homocysteine levels decreased in the supplement group compared to the placebo group.

Generally a large number of studies have observed that increasing folic acid and vitamin B6 and B12 concentrations decrease homocysteine levels.^{85, 92–100} Considering the findings of some improved cognition in elderly individuals with supplementation with B vitamins and folate there appears to be merit to the relationship between homocysteine and cognitive decline.

A recent Cochrane review of 8 RCTs found nothing significant or consistent enough to suggest that folic acid, (either with or without vitamin B12), had a beneficial effect on cognitive function in older people, unless possibly when baseline homocysteine levels were high.¹⁰¹

A very recent Australian double-blind, placebo-controlled, randomised trial administered 2mg of folate, plus 25mg of B6 and 400 μg of B12, or placebo to 299 men aged 75 years or older, for a period of 2 years.¹⁰² They found that those in the treatment group had significantly lower levels of Aβ protein 1–40 than the placebo group. While the participants in this sample were dementia free, the study demonstrated the possibility of a simple AD prevention strategy given that Aβ protein was lowered significantly with B vitamin supplementation.¹⁰²