Alzheimer Dementia – do diets help?

27th August 2023, Dr Chee L Khoo

Alzheimer Dementia

We talked about a number of monoclonal antibody (-mab) treatment for Alzheimer Dementia (AD) that have made headlines recently. We explore how (non) exciting the results of the clinical trials were including adverse effects. We also touched on how similar in efficacy the new wonder drugs are when compared with older existing anti-cholinesterases. Are the new drugs really that much better? The arrivals of the -mabs were recently well publicised in current affairs programs which has led to many patients coming in enquiring about this wonder class of drugs for AD. It has also spurred many patient to ask whether any diets or any supplements may help prevent AD or slow down the decline since existing agents including the -mabs are not that exciting. It so happens that a trial looking at the MIND Diet to prevent cognitive decline was published this week.

We don’t fully understand the aetiology of AD although it is believed that lifestyle factors may influence the risk of developing Alzheimer’s disease. These factors are physical activity, smoking, alcohol consumption and diet [1,2]. Despite common knowledge that diet has an impact on the risk of developing Alzheimer’s disease, literature data are still scarce and arouse a lot of controversy. Studies often discuss food groups, or a specific product and the nutrients that they contain. Their role is to assess which food elements have neuroprotective properties and may potentially impact the risk of developing Alzheimer’s disease. In this aspect antioxidants, B vitamins, and polyunsaturated fatty acids arouse the most significant interest.

The Mediterranean diet is characterised by high consumption of vegetables, fruits, nuts, legumes, unrefined grains and low consumption of meat and dairy products. The total fat content may be moderate or high, ranging from 30–40% of the total daily energy requirement. The diet include fish and nuts containing omega-3 fatty acids, wine containing polyphenols, and fruits, vegetables, and grains containing antioxidants. These nutrients are thought to be neuroprotective.

Dietary Approaches to Stop Hypertension, or DASH, is a diet recommended for people who want to prevent or treat hypertension. It is based on product groups such as fruit, vegetables, and low-fat dairy products. It also includes whole grains, lean meats, fish, nuts, and legumes. Compared to the Mediterranean diet, the DASH diet has less fat especially saturated fats and less salt.

The Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons is randomised, controlled trial involving older adults >65 years without cognitive impairment but with a family history of dementia, a body-mass >25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction (3). The MIND diet, is a hybrid of the Mediterranean and the DASH diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia.

The primary end point was the change from baseline in a global cognition score and four cognitive domain scores. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)–derived measures of brain characteristics.

301 were assigned to the MIND-diet group and 303 to the control-diet group. 93.4% of participants completed the trial. At baseline, the mean BMI between 33-34; 50% of participants had diabetes and 15% had hypertension. Dietary counselling for the MIND-diet group included instructions to incorporate foods from the MIND diet and to use MIND diet recipes for behavioural strategies to lose weight, to keep exercise levels the same as at baseline. The results of biochemical analyses of antioxidant nutrient levels in blood (lutein and zeaxanthin and alpha and beta carotene) supported adherence to the MIND diet in the MIND diet group. Dietary counselling for the control-diet group consisted of an equivalent frequency of consultation but focused on calorie tracking, portion control, and behavioural strategies to lose weight (e.g., coaching, goal setting, and mindful eating techniques) without changing the types of foods consumed. Both groups received equivalent amounts of support with respect to mild caloric restriction with the aim of achieving a weight loss of 3 to 5% by year 3.

From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardised units in the MIND-diet group and 0.170 standardized units in the control-diet group. However, the mean difference of 0.035 standardized units was not statistically.

While this trial did not demonstrate the superiority of the MIND diet over a controlled diet with mild calorie restriction, The effects of a healthy diet on brain health are supported by findings from previous observational studies (4-11) and some evidence links high consumption of green leafy vegetables, nuts and berries, and olive oil with a reduction in the hallmark neuropathologic features of Alzheimer’s disease (12-15). It is thought that antioxidant and anti-inflammatory capacities of certain foods is protective of brain functioning and against cognitive decline. Animal studies have shown that Vitamin E and Omega-3 fatty acids protects against lipid peroxidation, neuron loss, β-amyloid deposition, and decline in memory and learning. However, mechanistic evidence of these effects in humans is not well established.

Perhaps, the duration of this trial was too short to demonstrate benefits. Perhaps, these participants were too “healthy”. While 50% of participants had diabetes, we do not know how well controlled the diabetes was. 4% had heart disease in both groups and 3% in the MIND diet group had strokes while 1.7% in the control group had a history of strokes. Both groups received counselling on diet which may improve diet quality in both groups. Both groups lost weight which may protect against cognitive decline.

According to WHO, the Mediterranean diet can be recommended for adults with normal cognitive function and for people with mild cognitive impairment to reduce the risk of developing cognitive decline and dementia. In the case of Alzheimer’s disease, more research is still needed to assess the impact of the Mediterranean diet on this disease entity [16].

References:

  1. Garre-Olmo, J. Epidemiology of Alzheimer’s disease and other dementias. Rev. Neurol. 2018, 66, 377–386.
  2. Alzheimer’s Association. Alzheimer’s Association 2016 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dement. 2016, 12, 459–509
  3. Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons. L.L. Barnes, K. Dhana, X. Liu, et al. N Engl J Med 2023;389:602-11. DOI: 10.1056/NEJMoa2302368
  4. Yuan C, Chen H, Wang Y, Schneider JA, Willett WC, Morris MC. Dietary carotenoids related to risk of incident Alzheimer dementia (AD) and brain AD neuropathology: a community-based cohort of older adults. Am J Clin Nutr 2021; 113: 200-8.
  5. Booth SL, Shea MK, Barger K, et al. Association of vitamin K with cognitive decline and neuropathology in community-dwelling older persons. Alzheimers Dement (N Y) 2022; 8(1): e12255.
  6. Morris MC, Tangney CC, Wang Y, et al. MIND diet slows cognitive decline with aging. Alzheimers Dement 2015; 11:1015-22.
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  9. van de Rest O, Berendsen AA, Haveman-Nies A, de Groot LC. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr 2015; 6: 154-68.
  10. Devore EE, Kang JH, Breteler MMB, Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol 2012; 72: 135-43.
  11. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with agerelated cognitive change. Neurology 2006; 67: 1370-6.
  12. Wagner M, Agarwal P, Leurgans SE, et al. The association of MIND diet with cognitive resilience to neuropathologies. Alzheimers Dement 2023 February 28 (Epub ahead of print).
  13. Agarwal P, Holland TM, James BD, et al. Pelargonidin and berry intake association with alzheimer’s disease neuropathology: a community-based study. J Alzheimers Dis 2022; 88: 653-61.
  14. Agarwal P, Leurgans SE, Agrawal S, et al. Association of Mediterranean-DASH intervention for neurodegenerative delay and Mediterranean diets with Alzheimer disease pathology. Neurology 2023; 100(22): e2259-e2268.
  15. Dhana K, James BD, Agarwal P, et al. MIND diet, common brain pathologies, and cognition in community-dwelling older adults. J Alzheimers Dis 2021; 83: 683-92.
  16. World Health Organization. Global Status Report on the Public Health Response to Dementia; World Health Organization: Geneva, Switzerland, 2021; Available online: https://Apps.Who.Int/Iris/Handle/10665/344701 (accessed on 31 January 2022).