Michel: Is It Possible to Delay or Prevent Age-Related Cognitive Decline?
Korean Journal of Family Medicine 2016;37(5):263-266.
Academic Geriatric Department, Geneva University, Geneva, Switzerland.
Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published.
This inventory of the major modifiable dementia risk factors, as well as the composition and results obtained by the proposed dementia risk prediction score, highlight the importance of midlife cardio-, neuro-, and reno-vascular risk factors. As a reminder, these are: midlife obesity, sedentary lifestyle, diabetes, hypercholesterolemia, smoking, hypertension, atrial fibrillation, and chronic kidney disease.
However, this does not justify not searching for a viable alternative. Given the considerable decline in incidence reported in the recent paper based on the 20 year follow-up of the Framingham study,4) it seems necessary to take another look at the new developments in the field of prevention of cognitive decline. Four types of studies need to be analyzed.
Currently, there are three ongoing RCTs for the prevention of cognitive impairment based on multidomain interventions, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), Multidomain Alzheimer Prevention Study (MAPT), and PreDIVA trials.21) So far, only the results of the FINGER (FINnishGERiatric) study are known. This was a double blind RCT of 1,260 individuals aged 60–77 years with a CAIDE dementia score >6. The intervention group (n=631), which benefited from a multidomain intervention (comprising diet, exercise, cognitive training, vascular risk monitoring) for 2 years was compared to a control group (n=629), who received only general health advice. The primary outcome was the comprehensive neuropsychological test battery (NTB) Z-score (a composite score based on results from 14 tests, calculated as Z-scores, standardized to the baseline mean and standard deviations, with higher scores suggesting better performance). The estimated mean change in the NTB Z-score at 2 years was better (P=0.030) in the intervention group (0.20±0.51) compared to the control group (0.16±0.51). Thus, the FINGER study has shown that a multi-modal intervention could improve or maintain cognitive functioning in at-risk older adults.22) Undoubtedly, the results of the MAPT and PreDIVA will be the focus of much attention after such encouraging results from the FINGER study.
Up to now, only study protocols have been published for studies in this domain, of which several have just started (between 2012 and 2014). The studies target autosomal dominant early-onset Alzheimer's disease (two) and asymptomatic Alzheimer's disease (one).21) Results will be eagerly awaited.
How can we conclude this editorial, other than by stressing that regardless of the clinical presentation of the first symptoms of dementia, the major modifiable risk factors remain of cardio-, neuro-, and renovascular origin. Consequently, as a primary priority, health promotion and midlife prevention need to target these. A systematic search of PubMed and the Cochrane Database from inception to July 2014 identified 19,906 published reviews on the same topic, as this editorial. Based on 323 selected papers, the authors of the review established two kinds of grade 1 recommendations. Dietary recommendations including intake of folate, vitamins C and E, as well as coffee, and long-term recommended treatments, including estrogen, statins, antihypertensives, and non-steroidal anti-inflammatory drugs.6) The results of the currently ongoing RCTs will probably provide a series of more scientifically based results regarding the interventions for delaying or preventing dementia.
The author would like to acknowledge Fiona Ecarnot for her assistance with the preparation of this manuscript.
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