Seeing the forest but missing some important trees

For decades, dementia research has focused on finding a pharmaceutical cure. This search has been frustrating, yielding little and ultimately shifting focus to targets that might be less causal of disease and more so by-products of a multifactorial disease process. Furthermore, because dementia is not a unitary disease, but rather a set of symptoms with many different underlying causes (eg, Alzheimers disease, vascular dementia, lewy body dementia, and fronto-temporal dementia), any one future cure will leave a large swath of the population wanting. Two landmark Lancet Commissions in 20171Livingston G Sommerlad A Orgeta V et al.Dementia prevention, intervention, and care.Lancet. 2017; 390: 2673-2734Summary Full Text Full Text PDF PubMed Scopus (2780) Google Scholar and 2020,2Livingston G Huntley J Sommerlad A et al.Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet. 2020; 396: 413-446Summary Full Text Full Text PDF PubMed Scopus (1510) Google Scholar showed that there are likely multiple risk factors for dementia (eg, low education, pollution, hearing loss, and depression) that are potentially modifiable. That is, if we can address these risk factors early enough and adequately, we might be able to prevent a significant portion of dementia cases. Encouragingly, multiple studies are now funded and underway internationally to test that hypothesis.3Kivipelto M Mangialasche F Snyder HM et al.World-wide FINGERS network: a global approach to risk reduction and prevention of dementia.Alzheimers Dement. 2020; 16: 1078-1094Crossref PubMed Scopus (112) Google Scholar Too little research has focused on those people already diagnosed with dementia. What if modifying some of the same risk factors to prevent dementia could also modify the trajectory of dementia once the process is underway? Thus, the study by Gail Mountain and colleagues4Mountain G Cooper CL Wright J et al.The Journeying through Dementia psychosocial intervention versus usual care study: a single-blind, parallel group, phase 3 trial.Lancet Healthy Longev. 2022; 3: e276-e285Summary Full Text Full Text PDF Scopus (1) Google Scholar published in The Lancet Health Longevity, although ultimately yielding negative findings, is important. The Journeying through Dementia (JtD) study assessed the clinical benefits and cost-effectiveness of a psychosocial intervention designed to promote wellbeing and independence in patients with dementia. In this phase 3, single-blind, parallel group, phase 3 randomised trial, 13 NHS sites across England recruited patients with mild dementia who were living in the community. Participants were randomly assigned to receive either the JtD intervention or usual care. The JtD intervention consisted of 12 group sessions and four one-to-one sessions delivered in the community. 480 patients were randomly assigned (241 [50%] patients to the JtD group and 239 [50%] patients to the standard care group). Intervention adherence was very good, with 68% of patients in the JtD group attending at least ten of the 16 group and one-to-one sessions. The intervention was not found to be more efficacious than standard care for the main outcome of dementia-related quality of life; additionally, the intervention was not found to be cost-effective. Although disappointing, the study showed the feasibility and acceptability of implementing a relatively complex psychosocial intervention, including recruiting and retaining people with dementia. The study might provide us with a roadmap for future research, including considering other endpoints that might be modifiable through intervention. What are some possible lessons learned? The study was not specifically designed to specifically involve carers, though carers could participate if the person they cared for agreed to their participation. There is ample literature to show the crucial effect that carers have on outcomes in people with dementia.5Burton A Rapaport P Palomo M et al.Clinical and cost-effectiveness of a new psychosocial intervention to support Independence in Dementia (NIDUS-family) for family carers and people living with dementia in their own homes: a randomised controlled trial.Trials. 2021; 22: 865Crossref PubMed Scopus (3) Google Scholar Therefore, the decision not to involve carers explicitly and to a greater extent seems like a missed opportunity. Although people with mild dementia do not typically require help with activities of daily living, they might depend on carers for instrumental activities of daily living and other aspects of quality of life; 354 (74%) of the 480 patients in the JtD trial4Mountain G Cooper CL Wright J et al.The Journeying through Dementia psychosocial intervention versus usual care study: a single-blind, parallel group, phase 3 trial.Lancet Healthy Longev. 2022; 3: e276-e285Summary Full Text Full Text PDF Scopus (1) Google Scholar lived with others, with 313 (65%) patients living with a spouse or partner, suggesting that carers might have played a large role in supporting participants. The absence of measuring the effect of the intervention on carers seems like a large missing piece and an important note for future trials. There was no emphasis on behavioural and psychological symptoms of dementia (BPSD) other than measures of depression and anxiety used typically in older patients without BPSD. These symptoms (eg, agitation, psychosis, depression, anxiety, and disinhibition) are nearly ubiquitous in people with dementia, including in patients with mild dementia.6Kales HC Gitlin LN Lyketsos CG Assessment and management of behavioral and psychological symptoms of dementia.BMJ. 2015; 350: h369Crossref PubMed Scopus (564) Google Scholar Typically, BPSD drive the course of dementia more than memory impairment, and the effect of BPSD on carers often determines patient outcomes, such as emergency department visits, hospitalisations, and nursing home placement. Put succinctly, BPSD are perhaps the rate-limiting step to quality of life for people with dementia and their families and create most of the negative associated outcomes. Interventions in people without dementia that do not include or conceptualise BPSD as central would ignore a key factor in disease trajectory and progression. Because of BPSD, there are extremely high rates of psychotropic use in people with dementia.7Maust DT Strominger J Kim HM et al.Prevalence of central nervous system-active polypharmacy among older adults with dementia in the US.JAMA. 2021; 325: 952-961Crossref PubMed Scopus (10) Google Scholar This includes high rates of antidepressant, benzodiazepine, other anti-anxiety medication, sleep drug, and antipsychotic use in early dementia. Examining the effect of interventions on rates of psychotropic use in people with dementia is crucial. The study by Mountain and colleagues4Mountain G Cooper CL Wright J et al.The Journeying through Dementia psychosocial intervention versus usual care study: a single-blind, parallel group, phase 3 trial.Lancet Healthy Longev. 2022; 3: e276-e285Summary Full Text Full Text PDF Scopus (1) Google Scholar should be lauded for its ambition and large sample size of participants who are often difficult to recruit and retain. Additionally, although the results were negative, the study does provide the field with the key message that psychosocial interventions are feasible and probably highly acceptable for people with early dementia. I declare no competing interests. The Journeying through Dementia psychosocial intervention versus usual care study: a single-blind, parallel group, phase 3 trialIn common with other studies, the JtD intervention was not proven effective. However, this complex trial successfully recruited and retained people with dementia without necessarily involving carers. Additionally, people with dementia were actively involved as participants and study advisers throughout. More research into methods of measuring small, meaningful changes in this population is needed. Questions remain regarding how services can match the complex, diverse, and individual needs of people with mild dementia, and how interventions to meet such needs can be delivered at scale. Full-Text PDF Open Access