Association of trajectories of depressive symptoms with vascular risk, cognitive function and adverse brain outcomes: The Whitehall II MRI sub-study

Abstract

Background: Trajectories of depressive symptoms over the lifespan vary between people, but it is unclear whether these differences exhibit distinct characteristics in brain structure and function. Methods: In order to compare indices of white matter microstructure and cognitive characteristics of groups with different trajectories of depressive symptoms, we examined 774 participants of the Whitehall II Imaging Sub-study, who had completed the depressive subscale of the General Health Questionnaire up to nine times over 25 years. Twenty-seven years after the first examination, participants underwent magnetic resonance imaging to characterize white matter hyperintensities (WMH) and microstructure and completed neuropsychological tests to assess cognition. Twenty-nine years after the first examination, participants completed a further cognitive screening test. Results: Using K-means cluster modelling, we identified five trajectory groups of depressive symptoms: consistently low scorers ("low"; n=505, 62.5%), a subgroup with an early peak in depression scores ("early"; n=123, 15.9%), intermediate scorers ("middle"; n=89, 11.5%), a late symptom subgroup with an increase in symptoms towards the end of the follow-up period ("late"; n=29, 3.7%), and consistently high scorers ("high"; n=28, 3.6%). The late, but not the consistently high scorers, showed higher mean diffusivity, larger volumes of WMH and impaired executive function. In addition, the late subgroup had higher Framingham Stroke Risk scores throughout the follow-up period, indicating a higher load of vascular risk factors. Conclusions: Our findings suggest that tracking depressive symptoms in the community over time may be a useful tool to identify phenotypes that show different etiologies and cognitive and brain outcomes.

Microvascular Contribution to Late-Onset Depression: Mechanisms, Current Evidence, Association With Other Brain Diseases, and Therapeutic Perspectives

“…Recent longitudinal data showed that only individuals with depressive symptoms that increased in late-life, and no other trajectories of depressive symptoms across the life course, had higher white matter hyperintensity volumes (71). In addition, only this trajectory has been associated with greater decline in executive function (71), and higher risk of dementia (72,73).…”

Associations of depression and regional brain structure across the adult lifespan: Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

“…However, whether brain differences reflect vulnerability or long-term ‘scarring’ consequences cannot be concluded from our cross-sectional study. Longitudinal studies have suggested that differences might be related to depression onset or vulnerability rather than be the result of depressive episodes ( Binnewies et al, 2021 , Demnitz et al, 2020 ), although findings are inconsistent ( Dohm et al, 2017 ).…”

Mediterranean-DASH Intervention for Neurodegenerative Delay diet and risk of dementia: three prospective studies and meta-analysis of cohort studies

“…Depressive symptom was assessed using the Center for Epidemiologic Studies Depression Scale-8 (CES-D 8) for HRS participants, and participants scoring 4/8 or above were defined as having depressive symptom[35]. In the FOS and WII, a 20-item CES-D was used, and a score of 16/60 or above indicated depressive symptom[36,37]. In the FOS and WII where physical and blood examination was regularly administered, we additionally identified participants with hypertension [38](with anti-hypertensive medication or systolic blood pressure >=130 mmHg or diastolic blood pressure>=80 mmHg), diabetes [39](with oral hypoglycemic medication or insulin use, fasting blood glucose concentrations ≥126 mg/dL, or non-fasting blood glucose concentrations ≥200 mg/dL), and hypercholesterolemia [40](with cholesterol-lowering medication or total cholesterol concentrations ≥200 mg/dL, i.e., 5.20 mmol/L).…”