A steady but certain shift towards the integration of evidence-based tools to enhance traditional methods of dietary assessment is currently emerging in the field of nutrition science. This is noteworthy, because much of our understanding of dietary associations in relation to Alzheimer’s disease (AD) and other late onset dementia (LOD) forms has derived from self-administered dietary assessments which are prone to biases and reporting errors.
Specifically, the integration of -omics technologies into the evaluation of dietary exposures heralds a new era of research that can be more robust with potential to improve reliability and offer novel insights to pre-disease indicators and preventive targets in cognitive aging and dementia.
Recent years saw a plethora of publications from non-pharmacological interventional studies such as the FINGER randomized controlled trial (RCT) providing evidence that diet, as part of a multi-domain lifestyle intervention, can contribute to significantly mitigate decline in cognitive performance and potentially delay the onset or progression of AD and other types of dementia (1). These promising results, based on simultaneous management of several vascular and lifestyle related risk factors, in which the intervention group were assigned a multidomain intervention consisting of diet, exercise, cognitive training, vascular risk monitoring versus the control group assigned general health advice, showed efficacy after a 2 year period in improving cognitive performance in at-risk, but cognitively unimpaired and/or mildly impaired individuals (2). This was pivotal because interest in lifestyle modifications to reduce disease prevalence was affirmed and personalised strategies/optimal timing became discussion points.
The increasing awareness that pathological changes in AD-LODs develop many years prior to clinical disease onset and the results of several observational and interventional studies has led the field to acknowledge that the pre-clinical or early clinical stages are the optimal time points for intervention; thus, attention has shifted towards health-promoting behaviours such as healthy diet, maintaining an optimal weight, physical and mental activities and social interactions, in addition to potential pharmacological therapies, if and when novel disease modifying medicines of proven efficacy and cost effectiveness become available.
Diet and nutrition are viable targets for strategies aimed at preserving cognitive health in older adults and have become a focus in dementia related studies. Moreover, there has been a gradual shift from single nutrient analyses towards dietary pattern analyses, reflecting trends in nutritional epidemiology, in which synergistic effects of food combinations and possible nutrient interactions are deemed more informative (3).
Despite accruing evidence from a wealth of epidemiological studies, showing that adherence to healthy dietary patterns, such as the Mediterranean, Nordic, DASH, MIND or anti-inflammatory diets may lend neuroprotective effects, and more recently, the ketogenic diet, in its capacity to alter brain metabolism (4–7), these findings have not translated uniformly into dietary guidelines, to improve cognitive health and disease burden reduction in older adults, due to inconsistencies in the literature.
In order to understand the precise effects of dietary intake on cognitive function and their mechanism of action, dietary assessment methodologies must be able to measure dietary intake as accurately as possible. As it stands, current methods of dietary assessment typically collect self-reported data through food-frequency questionnaire (FFQ), 24-hour recalls, or food diaries which are dependent on subject recall and cognitive functioning; all self-reported methodologies have considerable scope for measurement error and inherent bias, with under-reporting biased towards unhealthy foods and dietary energy intake and over-reporting towards healthier foods (8).
Also, there is potential error in estimating portion sizes and the limitation of the number of foods and dishes that have been directly analysed. Reporting is known to deteriorate further in the obese and likely to include significant inaccuracies in older populations. Prevalence of misreporting has been estimated as between 30–88% in epidemiological surveys (9). In large scale studies, use of FFQ’s are commonly applied, but since these are tailored to suit the population they serve, there is wide variation in number and range of items appearing on food lists.
Another limiting factor with traditional dietary assessment models is the limited number of nutrients that have been measured accurately in food. Evidence suggests that bioactive molecules in food such as polyphenols may play a role, but these molecules are not measured in most nutritional data sets. This limits the scope of understanding between the chemical composition of food and cognitive associations.
Reliability of dietary assessment is further compromised by analytical methods applying either a priori methodologies using constructed scores based on an underlying hypothesis and dietary guidelines which do not reflect entire dietary intake or a posteriori methods, applying data reduction techniques, such as principal component analysis, factor analysis, or cluster analysis to categorise on intercorrelations which provides insight to shared characteristics within a population but has limited comparability and reproducibility in other population samples. Both approaches are limited by pre-defined selections of food and nutrient groupings resulting in varying interpretations of dietary exposures and disease risk.
In recent years, the advent of online dietary assessment tools has made data collection and analysis much easier, albeit not mitigating the biases, as outlined above; also including technological competence in older adults, recently noted as a possible confounder for reporting accuracy; a feasibility study on use of online dietary recalls among older adults indicated that participants who completed multiple recalls reported higher self-confidence with technology and a higher technology readiness score than those who did not complete any recalls (10). There is, still, a need for evidence-based tools to be evaluated for validation and reliability in study outcomes and clarity in mechanisms that might be protective against dementia. We therefore propose a focus on applying metabolomics as a validation tool and framework for investigating the immediate or cumulative effects of diet on cognitive status and decline.