Intervention studies and meta-analyses as references

Here you will find a continuously expanding collection of studies with a focus on intervention studies and meta-analyses. Further studies are referred to on the corresponding content pages.

Why intervention studies? – Against narrow-mindedness!

During your journey in the self-responsible prevention and treatment of cognitive impairment and dementia, you will often (even frequently) experience an indescribable narrow-mindedness from many doctors,  who denigrate changes in lifestyle and  the supply of vital resources and the reduction of pollutants as a “fantasyland” approach to treatment.

The studies listed below clearly show that specific interventions, whether with micronutrients, sports, diet, sleep hygiene or mental measures, can clearly restore lost cognitive abilities. They thus supply you with important argumentation aids on your difficult path through the narrow-mindedness and perplexity of conventional medicine. The studies are sorted by category and the most recent studies are listed first. See for yourself:


Nutrition

General

Bayer-Carter JL, Green PS, Montine TJ, et al. Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment. Arch Neurol. 2011;68(6):743–752. doi:10.1001/archneurol.2011.125
https://pubmed.ncbi.nlm.nih.gov/21670398/

Conclusion: Our results suggest that diet may be a strong environmental factor that modulates the risk of Alzheimer’s disease through its effects on the concentrations of Aβ42, lipoproteins, oxidative stress and insulin in the central nervous system.

de la Rubia Ortí JE, García-Pardo MP, Drehmer E, et al. Improvement of Main Cognitive Functions in Patients with Alzheimer’s Disease after Treatment with Coconut Oil Enriched Mediterranean Diet: A Pilot Study. J Alzheimers Dis. 2018;65(2):577–587. doi:10.3233/JAD-180184
https://pubmed.ncbi.nlm.nih.gov/30056419/

Conclusion: The isocaloric, coconut oil-enriched Mediterranean diet appears to improve cognitive functions in patients with Alzheimer’s disease, with differences according to gender and severity of the disease, although further studies in this direction are needed.


Omega 3 fatty acids

Raji, C. A. et al. (2014) ‘Regular Fish Consumption and Age-Related Brain Gray Matter Loss’, American Journal of Preventive Medicine, 47(4), pp. 444–451. doi: 10.1016/j.amepre.2014.05.037.
https://www.ncbi.nlm.nih.gov/pubmed/25084680

Conclusion: The consumption of baked or fried fish is associated with larger amounts of grey matter, regardless of the omega-3 fatty acid content. These findings suggest that a combination of lifestyle factors affects brain health, contributing to the growing body of evidence that late life brain health prevention strategies need to start decades earlier.

Shinto L, Quinn J, Montine T, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis. 2014;38(1):111-20.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886557/pdf/nihms539809.pdf

Conclusion: The combination of omega 3 plus alpha lipoic acid slowed the cognitive and functional decline in Alzheimer’s over 12 months.


Probiotics 

Hwang YH, Park S, Paik JW, et al. Efficacy and Safety of Lactobacillus Plantarum C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2019;11(2):305.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412773/

Conclusion: The results of this clinical trial suggest that DW2009 can be safely administered to enhance cognitive function in individuals with MCI. Increased serum BDNF levels after administering DW2009 may provide preliminary insight into the underlying effects of cognitive improvement, which suggests the importance of the gut-brain axis in ameliorating cognitive deficits in MCI.

Kobayashi Y, Kinoshita T, Matsumoto A, Yoshino K, Saito I, Xiao JZ. Bifidobacterium Breve A1 Supplementation Improved Cognitive Decline in Older Adults with Mild Cognitive Impairment: An Open-Label, Single-Arm Study. J Prev Alzheimers Dis. 2019;6(1):70–75.
https://pubmed.ncbi.nlm.nih.gov/30569089/

Conclusion: The present study showed that oral supplementation of B. breve A1 in participants with MCI improved cognitive function, thus suggesting the potential of B. breve A1 for improving cognitive function and maintaining quality of life of the elderly. Further randomized, double-blind placebo-controlled studies are worth conducting to examine the beneficial effect of B. breve A1.


Tea

Liu X, Du X, Han G, Gao W. Association between tea consumption and risk of cognitive disorders: A dose-response meta-analysis of observational studies. Oncotarget. 2017;8(26):43306-43321. doi:10.18632/oncotarget.17429
https://www.ncbi.nlm.nih.gov/pubmed/28496007

Conclusion: Tea consumption is inversely and linearly related to the risk of cognitive disorders.


Lifestyle interventions / Combined approaches

Rosenberg A, Ngandu T, Rusanen M, et al. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial. Alzheimers Dement. 2018;14(3):263–270. doi:10.1016/j.jalz.2017.09.006
https://pubmed.ncbi.nlm.nih.gov/29055814/

Conclusion: The FINGER intervention was beneficial regardless of the characteristics of the participants and can therefore be carried out in a large older population with an increased risk of dementia.

Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1007–1014.
https://www.ncbi.nlm.nih.gov/pubmed/25681666

Conclusion: Strict adherence to all three diets can reduce the risk of Alzheimer’s. Even moderate adherence to the MIND diet can reduce the risk of Alzheimer’s.

Morris MC, Tangney CC, Wang Y, et al. MIND diet slows cognitive decline with aging. Alzheimers Dement. 2015;11(9):1015–1022.
https://www.ncbi.nlm.nih.gov/pubmed/26086182

Conclusion: The results of the study suggest that the MIND diet significantly slows down cognitive decline with age. A replication of these results in a nutrition intervention study would be necessary to verify their relevance for brain health.

Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255–2263. doi:10.1016/S0140-6736(15)60461-5
https://pubmed.ncbi.nlm.nih.gov/25771249/

Conclusion: The results of this large, long-term, randomized, controlled study suggest that a multi-domain intervention could improve or maintain cognitive function in older risk individuals from the general population.


Micronutrients

Alpha lipoic acid

Shinto L, Quinn J, Montine T, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis. 2014;38(1):111-20.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886557/pdf/nihms539809.pdf

Conclusion: The combination of omega 3 plus alpha lipoic acid slowed the cognitive and functional decline in Alzheimer’s over 12 months.

Hager, Klaus & Kenklies, M & Mcafoose, Jordan & Engel, J & Muench, Gerald. (2007). ??-Lipoic acid as a new treatment option for Alzheimer’s disease – A 48 months follow-up analysis. Journal of neural transmission. Supplementum. 72. 189-93. 10.1007/978-3-211-73574-9_24.

Conclusion: In patients with mild dementia (ADAScog < 15) the disease progressed extremely slowly (ADAScog: +1.2 points/year, MMSE: -0.6 points/year), in patients with moderate dementia about twice as fast. However, the progression seems to be dramatically lower than the data reported for untreated patients or patients with cholinesterase inhibitors in the second year of the long-term studies. Although this study was not double-blind, placebo-controlled and randomized, the data suggest that treatment with alpha lipoic acid may be a successful “neuroprotective” treatment option for AD.

Vitamin B

Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935890/pdf/pone.0012244.pdf

Conclusion: The accelerated rate of brain atrophy in elderly people with mild cognitive impairment can be slowed down by treatment with homocysteine-lowering B vitamins. Sixteen percent of people over 70 years of age have mild cognitive impairment and half of them develop Alzheimer’s disease. Since accelerated brain atrophy is a feature of people with mild cognitive impairment who develop Alzheimer’s disease, studies are needed to see whether the same treatment delays the development of Alzheimer’s disease.

Vitamin D

Chai, B., Gao, F., Wu, R. et al. Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: an updated meta-analysis. BMC Neurol 19, 284 (2019). https://doi.org/10.1186/s12883-019-1500-6
https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1500-6

Conclusion: There are significant associations between vitamin D deficiency and both dementia and AD. There are stronger associations between severe vitamin D deficiency (< 10 ng/ml) and both dementia and AD compared to moderate vitamin D deficiency (10-20 ng/ml).

Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O. Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis. 2013;37(1):147–171. doi:10.3233/JAD-130452
https://pubmed.ncbi.nlm.nih.gov/23948884/

Conclusion: Lower serum 25OHD concentrations predict executive dysfunction, especially in terms of mental shift, information updating and processing speed. The association with episodic memory remains uncertain.

Chaves M, Toral A, Bisonni A, et al. Treatment with vitamin D and slowing of progression to severe stage of Alzheimer’s disease, published correction appears in Vertex. 2014 May-Jun;25(115):164. Basallo, María José [corrected to García Basalo, María José]]. Vertex. 2014;25(114):85–91.
https://pubmed.ncbi.nlm.nih.gov/25153973/

Conclusion: The time of progression to the severe stage of Alzheimer’s disease was slower in patients under treatment with vitamin D than in untreated patients (5.4 ± 0.4 years vs. 4.4 ± 0.16 years, p=0.003). Treatment with vitamin D may be an independent protective factor in the progression of Alzheimer’s disease.

Vitamin E (Alpha-Tocopherol)

Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311(1):33-44 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109898/pdf/nihms557752.pdf

Conclusion and relevance: Patients with mild to moderate AD, 2000 IU/d of alpha-tocopherol compared to placebo showed a slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha-tocopherol. These results suggest a benefit of alpha-tocopherol in mild to moderate AD by slowing functional decline and reducing the burden on caregivers.

Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer’s Disease, N Engl J Med 1997; 336:1216-1222
https://www.ncbi.nlm.nih.gov/pubmed/9110909

Conclusion: In patients with moderate impairment from Alzheimer’s disease, treatment with selegiline or alpha-tocopherol slows down the progression of the disease.


Sport and exercise

Morris JK, Vidoni ED, Johnson DK, et al. Aerobic exercise for Alzheimer’s disease: A randomized controlled pilot trial. PLoS One. 2017;12(2):e0170547. Published 2017 Feb 10. doi:10.1371/journal.pone.0170547
https://pubmed.ncbi.nlm.nih.gov/28187125/

Conclusion: Aerobic exercise in early Alzheimer’s disease is associated with benefits for functional ability. Exercise-related improvements in cardiorespiratory fitness have been associated with improved memory performance and reduced hippocampal atrophy, suggesting that cardiorespiratory fitness gains may be important in increasing brain benefits.

Hoffmann K, Sobol NA, Frederiksen KS, et al. Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial. J Alzheimers Dis. 2016;50(2):443–453. doi:10.3233/JAD-150817
https://pubmed.ncbi.nlm.nih.gov/26682695/

Conclusion: This is the first randomized, controlled study with supervised moderate to high intensity exercise in patients with mild Alzheimer’s disease. The exercise reduces neuropsychiatric symptoms in patients with mild Alzheimer’s, with possible additional benefits of maintaining cognitive performance in a subgroup of patients who exercise with high participation and intensity.

Raji, C. A., Merrill, D. A., Eyre, H., Mallam, S., Torosyan, N., Erickson, K. I., Lopez, O. L., Becker, J. T., Carmichael, O. T., Gach, H. M., Thompson, P. M., Longstreth, W. T., Kuller, L. H., 2016. Longitudinal relationships between caloric expenditure and gray matter in the cardiovascular health study. Journal of Alzheimer’s disease : JAD 52 (2), 719-729.
http://view.ncbi.nlm.nih.gov/pubmed/26967227

Conclusion: The increasing energy output during a variety of physical activities is related to larger amounts of grey matter in older people, regardless of cognitive status.

Yang SY, Shan CL, Qing H, et al. The Effects of Aerobic Exercise on Cognitive Function of Alzheimer’s Disease Patients. CNS Neurol Disord Drug Targets. 2015;14(10):1292–1297. doi:10.2174/1871527315666151111123319
https://pubmed.ncbi.nlm.nih.gov/26556080/

Conclusion: In summary, a moderate intensity of aerobic exercise can improve cognitive function in patients with mild Alzheimer’s disease.

Varma, V. R. et al. (2015) ‘Low-intensity daily walking activity is associated with hippocampal volume in older adults’, Hippocampus, 25(5), pp. 605–615. doi: 10.1002/hipo.22397.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425252/

Conclusion: A larger sum, duration and frequency of total daily walking activity is associated with a larger hippocampal volume in older women but not in men. These relationships were specific to hippocampal volume compared to the thalamus, which is used as the control brain region, and remained significant for low-intensity walking activity, independent of moderate to high activity and self-reported exercise.

Baker LD, Frank LL, Foster-Schubert K, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010;67(1):71–79. doi:10.1001/archneurol.2009.307
https://pubmed.ncbi.nlm.nih.gov/20065132/

Conclusion: Using a strictly controlled methodology, this study provides support for an effective non-pharmacological intervention that improves executive control processes in older women at high risk of cognitive decline. In addition, our results suggest that gender bias in cognitive response may be related to gender differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.

 

 

 

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