Advances in the prevention of Alzheimer's disease and dementia

Abstract

Definitions and diagnostic criteria for all medical conditions are regularly subjected to reviews and revisions as knowledge advances. In the field of Alzheimer’s disease (AD) research, it has taken almost three decades for diagnostic nomenclature to undergo major re-examination. The shift towards presymptomatic and pre-dementia stages of AD has brought prevention and treatment trials much closer to each other than before. Here we discuss: (i) the impact of diagnostic reliability on the possibilities for developing preventive strategies for AD; (ii) the scientific evidence to support moving from observation to action; (iii) ongoing intervention studies; and (iv) the methodological issues and prospects for balancing strategies for high-risk individuals with those for broad population-based prevention. The associations between neuropathology and cognition are still not entirely clear. In addition, the risk factors for AD dementia and the neuropathological hallmarks of AD may not necessarily be the same. Cognitive impairment has a clearer clinical significance and should therefore remain the main focus of prevention. Risk/protective factors for dementia/AD need to be studied from a life-course perspective. New approaches in prevention trials include enrichment strategies based on genetic risk factors or beta-amyloid biomarkers (at least four ongoing pharmacological trials), and multidomain interventions simultaneously targeting various vascular and lifestyle-related risk factors (at least three ongoing trials). Experience from prevention programmes in other chronic diseases can provide additional methodological improvements. Building infrastructures for international collaborations is necessary for managing the worldwide public health problem of AD and dementia. The International Database on Aging and Dementia (IDAD) and the European Dementia Prevention Initiative (EDPI) are examples of ongoing international efforts aiming to improve the methodology of preventive studies and provide the basis for larger intervention trials.

CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia

“…Blood pressure, BMI and cholesterol tend to decline after midlife in individuals who develop dementia later on (Solomon et al, 2014).…”

“…Modifiable vascular and lifestyle-related risk factors have been shown to increase the risk of dementia (Solomon et al, 2014). Dementia risk scores have been developed in general populations (Kivipelto et al, 2006) (Barnes et al, 2009) (Jefferson et al, 2015), primary care or specialized units (Buratti et al, 2015) for the purpose of identifying at-risk individuals who could benefit from preventive interventions .…”

Advances in the therapy of Alzheimer’s disease: targeting amyloid beta and tau and perspectives for the future

“…Indeed, evidence from longitudinal observational studies shows that risk factors for dementia and AD are diverse biological and lifestyle-related factors (as summarized in TABLE 3 adapted from [15]). In contrast to epidemiological studies, less evidence is available from RCTs showing that interventions focusing on modifiable factors can reduce the risk of cognitive impairment and dementia/AD.…”

“…Growing evidence indicates that early identification of AD vascular risk factors and patient follow-up to assess modifiable risk factors (e.g., obesity, insulin resistance, diabetes, deficiency of w-3 polyunsaturated fatty acids in the diet, sedentary lifestyle and social isolation) may be a pillar of prevention. Indeed, a healthy diet coupled with physical and mental activity is increasingly applied as part of interventions in AD prevention trials [15]. As a result, research focused on preventing late-life dementias should develop ways of decreasing risk factors at both the societal and the personal levels [9].…”

The Canadian dementia challenge: Ensuring optimal care and services for those at risk or with dementia throughout the country

“…7 Recent experimental therapeutic efforts targeting the amyloidopathy of AD have had disappointing results, 8,9 with many pharmaceutical companies leaving this field of research, given the costs of development failure. At the same time, approximately 28% of the risk for AD lies in preventable and treatable risks such as diabetes mellitus, midlife hypertension and obesity, physical inactivity, depression, smoking, and low educational attainment.…”