Is cognitive screening useful for long-term prediction of incident dementia?
Authors: Linda Chiu Wa Lam, Allen T C Lee
Journal: The Lancet Healthy Longevity (2021)

While approval of the first potentially disease-modifying medication for Alzheimer's disease is promising, there are mixed opinions and many practical issues still need to be resolved.1Cavazzoni P FDA's decision to approve new treatment for Alzheimer's disease.https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-diseaseDate: June 7, 2021Date accessed: June 16, 2021Google Scholar Advanced neuroimaging techniques have greatly enhanced early diagnosis of dementia. The Amyloid-Tau-Neurodegeneration framework for biomarker profiling of neurocognitive disorders attempted to shift the diagnostic paradigm from clinical syndromes to neuroimaging and biochemical evaluation of neurodegeneration, aiming towards identifying a presymptomatic phase of such diseases.2Jack Jr, CR Bennett DA Blennow K et al.NIA-AA research framework: toward a biological definition of Alzheimer's disease.Alzheimers Dement. 2018; 14: 535-562Summary Full Text Full Text PDF PubMed Scopus (3189) Google Scholar However, disease-specific investigation as a tool for community-based early screening is unlikely to be of high pragmatic value in the near future. As the most identifiable clinical feature of dementia, assessment on cognitive function has always been considered a core component in dementia screening. Use of cognitive assessments in dementia screening has high face validity. However, the situation appears to be much more complex. Owing to the heterogeneity of study settings, findings on how well cognitive screening can aid in disease identification have been inconsistent. In The Lancet Healthy Longevity, Marcos Machado-Fragua and colleagues attempted to address the various issues around this topic through a long-term follow-up study of a large sample of adults.3Machado-Fragua MD Dugravot A Dumurgier J et al.Comparison of the predictive accuracy of multiple definitions of cognitive impairment for incident dementia: a 20-year follow-up of the Whitehall II cohort study.Lancet Healthy Longev. 2021; 2: 407-416Summary Full Text Full Text PDF Google Scholar 5687 participants from the Whitehall II cohort study, with a mean age of 65·7 years (SD 5·9), were followed up for a median of 10·5 years (IQR 10·1–10·9), during which 270 (4·7%) participants were found to have incident dementia.3Machado-Fragua MD Dugravot A Dumurgier J et al.Comparison of the predictive accuracy of multiple definitions of cognitive impairment for incident dementia: a 20-year follow-up of the Whitehall II cohort study.Lancet Healthy Longev. 2021; 2: 407-416Summary Full Text Full Text PDF Google Scholar The authors explored seven different definitions of cognitive impairment including demographically adjusted cutoffs (ie, sex, age, education, and occupation). Their long-term prospective observations allowed for the inclusion of both poor cognitive performance, measured at a single timepoint, and cognitive decline as part of the definition for cognitive impairment. The thorough and systematic exploration of different definitions for cognitive impairment provide insight as to how cognitive screening could be applied for improved clinical detection of dementia. A cross-sectional evaluation with impaired cognitive performance might be indicative of dementia; however, there could be other non-dementia causes for cognitive impairment at a given timepoint. The incorporation of cognitive decline over a long observation period would improve detection of dementia-associated cognitive deterioration. As reported by Machado-Fragua and colleagues,3Machado-Fragua MD Dugravot A Dumurgier J et al.Comparison of the predictive accuracy of multiple definitions of cognitive impairment for incident dementia: a 20-year follow-up of the Whitehall II cohort study.Lancet Healthy Longev. 2021; 2: 407-416Summary Full Text Full Text PDF Google Scholar higher specificity (>94%) was found for definitions that included both poor cognitive performance and cognitive decline. However, the sensitivities for these combined criteria were only modest (21·6–22·4%). Moreover, the predictive utility for the different criteria did not outperform a demographic model including age, sex, and education only. This raises a question on the validity of cognitive assessment in the prediction of preclinical dementia in the community.4Owens DK Davidson KW et al.US Preventive Services Task ForceScreening for cognitive impairment in older adults: US Preventive Services Task Force recommendation statement.JAMA. 2020; 323: 757-763Crossref PubMed Scopus (81) Google Scholar Different factors could influence the performance characteristics of cognitive assessment in community-based studies. Participants of the Whitehall II cohort study were relatively young when baseline cognitive assessments were done in 2007–09. After 10 years of follow-up, the mean age of the cohort had not yet reached the peak for onset of major dementia such as Alzheimer's disease, which has been found to have an incidence of approximately two new cases per 1000 people aged 65–74 years, compared with 13 per 1000 people aged 75–84 years and 39 per 1000 people aged 85 years or older.5Alzheimer's Association2015 Alzheimer's disease facts and figures.Alzheimers Dement. 2015; 11: 332-384Summary Full Text Full Text PDF PubMed Scopus (1296) Google Scholar This is reflected by the relatively low overall 10-year incidence of dementia at the study end. For the majority of younger and healthy participants, subtle cognitive impairment might not be readily captured by cognitive assessment, thus affecting sensitivity analysis. As the authors do not report whether interval medical events happened during follow-up, it is possible that, for younger participants, events such as cerebrovascular accidents might have had a greater effect on cognitive performance during follow-up than a more general decline in cognitive function. The study findings reinforce that age, sex, and education are robust predictors for dementia. These well recognised patient factors can provide a sound basis for risk stratification when large-scale community screening for dementia is planned. There might, however, be a need to expand patient factors to include physical health and lifestyle to enhance predictive power.6Hou XH Feng L Zhang C Cao XP Tan L Yu JT Models for predicting risk of dementia: a systematic review.J Neurol Neurosurg Psychiatry. 2019; 90: 373-379Crossref PubMed Scopus (61) Google Scholar For high-risk groups, definitions of cognitive impairment inclusive of short-term cognitive decline might help to increase detection rates, whereas for low-risk groups, cognitive assessment should focus on more subtle deficits such as complex attention, executive function, and psychomotor speed. As highlighted by the Whitehall II cohort, the combination of cognitive criteria can provide high specificity. Participants who are identified as being at risk for dementia on the basis of these criteria might be considered for next-level advanced neuroimaging or biomarker evaluation for preclinical disease detection and classification. We declare no competing interests. Comparison of the predictive accuracy of multiple definitions of cognitive impairment for incident dementia: a 20-year follow-up of the Whitehall II cohort studyThese findings suggest that cognitive impairment in early old age might not be useful for dementia prediction, even when it is defined using longitudinal data on cognitive decline and thresholds of poor cognitive performance additionally defined by education or occupation. Full-Text PDF Open Access