Cognitive and social activities and long-term dementia risk – Authors' reply
Authors: Sarah Floud, Angela Balkwill, Gillian K Reeves, Richard Peto, Valerie Beral
Journal: The Lancet Public Health (2021)

The pathological processes that culminate in dementia tend to be gradual, with preclinical manifestations developing slowly over some years. Consistent with this slow progression, weight loss and reductions in physical activity can be seen at least a decade before any definite record of dementia.1Sabia S Dugravot A Dartigues JF et al.Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study.BMJ. 2017; 357j2709Crossref PubMed Scopus (153) Google Scholar, 2Stewart R Masaki K Xue QL et al.A 32-year prospective study of change in body weight and incident dementia: the Honolulu-Asia Aging Study.Arch Neurol. 2005; 62: 55-60Crossref PubMed Scopus (364) Google Scholar In prospective studies, reverse causation bias (whereby preclinical dementia causes behavioural and other changes) would be greater during the first decade after activities were recorded, particularly during the first 5 years, than during the second decade of follow-up. In the 20-year UK Million Women Study, with more than 30 000 incident cases of dementia, we found strong evidence of such reverse causation bias, in that associations during the first decade after physical, cognitive, and social activities were recorded largely disappeared during the second decade of follow-up (figure).3Floud S Balkwill A Sweetland S et al.Cognitive and social activities and long-term dementia risk: the prospective UK Million Women Study.Lancet Public Health. 2021; 6: e116-e123Summary Full Text Full Text PDF Scopus (6) Google Scholar The apparent excess of dementia during the first decade after the reporting of inactivity is likely to be a consequence of the gradual onset of inactivity, and not because inactivity causes dementia. During the second decade, however, when such reverse causation bias is minimised, there is little or no long-term effect of inactivity on dementia incidence. Similar evidence of reverse causation bias was found for physical, cognitive, and social activities (figure). Robert Friedland quotes two small studies to support the claim of the long-term risk of dementia associated with cognitive activities. One study included just ten nuns with dementia,4Snowdon DA Kemper SJ Mortimer JA Greiner LH Wekstein DR Markesbery WR Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.JAMA. 1996; 275: 528-532Crossref PubMed Google Scholar and the other included 193 people with probable or possible Alzheimer's disease and 358 controls, in which retrospectively reported historical behaviour information was compared for those and without the disease.5Friedland RP Fritsch T Smyth KA et al.Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members.Proc Natl Acad Sci USA. 2001; 98: 3440-3445Crossref PubMed Scopus (348) Google Scholar Asking about past activities after it is known who has and who does not have Alzheimer's disease is prone to differential recall and hence is unreliable. By contrast, a major strength of prospective studies is that activities are recorded years before the onset of a particular disease and can provide unbiased evidence about their long-term effects. UK prospective studies have the good fortune, largely by virtue of the extensive National Health Service databases, to achieve virtually complete follow-up for hospital visits for dementia and other conditions over many decades, by electronic linkage to its nationwide health records. This greatly facilitates the ability of the UK Million Women Study to show that short-term associations with inactivity are likely to reflect the consequences of the gradual onset of dementia, as well as reliably showing the lack of long-term effects of various activities on dementia incidence. We declare no competing interests. Cognitive and social activities and long-term dementia riskI read Sarah Floud and colleagues' Article on activities and dementia risk with concern.1 Considerable evidence supports the concept that cognitive and physical activities have a beneficial effect on the brain and that they protect against dementia development. Full-Text PDF Open AccessCognitive and social activities and long-term dementia risk: the prospective UK Million Women StudyLife has to be lived forwards, but can be understood only backwards. Long before dementia is diagnosed, there is a progressive reduction in various mental and physical activities, but this is chiefly because its gradual onset causes inactivity and not because inactivity causes dementia. Full-Text PDF Open Access