From dysphoria to anhedonia: Age-related shift in the link between cognitive and affective symptoms

Background Depression in aging shows heterogeneous symptoms across cognitive, affective, and neurobiological domains. Traditional categorical diagnoses may not capture these complex patterns, prompting a shift toward dimensional or domain-based approaches. We examined whether the symptoms that bridge cognition and affect differ by age, and explored their associations with brain structure.

Data from 756 young (≤45 years) and 1230 older (≥65 years) adults from the Cambridge Centre for Ageing and Neuroscience were analysed. Cognition was assessed using the Addenbrooke’s Cognitive Examination Revised, and depressive and anxiety symptoms with the Hospital Anxiety and Depression Scale. Graphical LASSO was used to construct cognitive-affective networks, testing for age-related differences in strength and bridging centrality measures. Building on these findings, we further examined the association between bridging symptoms, cognition, and gray matter volume (GMV).

Symptom strength centrality was similar across groups. However, in older but not in younger adults, depressive symptoms were more strongly connected to cognitive symptoms than anxiety symptoms. The primary bridging symptom shifted with age, from dysphoria in young adults to anhedonia in older adults. Follow-up analyses indicated that the anhedonia-to-dysphoria difference was associated with the relationship between GMV and cognition, particularly in older adults.

Cognitive-affective bridging symptoms differ with age, with anhedonia replacing dysphoria as the key bridge in older adults. This shift was linked to differences in how GMV relates to cognition in late life. These results highlight the need to target different symptoms to alleviate cognitive-affective manifestations across the lifespan. Competing Interest Statement The authors have declared no competing interest. Funding Statement Cam-CAN research was supported by the Biotechnology and Biological Sciences Research Council (BB/H008217/1). DH was supported by an Israel Science Foundation Mavri fellowship. NW was supported by an Israel Science Foundation Personal Research Grant (1603/22). We are grateful to the Cam-CAN respondents and their primary care teams in Cambridge for their participation in this study. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All data used for this work are publicly available upon signing data sharing agreement on https://cam-can.mrc-cbu.cam.ac.uk/dataset/. Code used to analyse the data and generate the figures is available on https://github.com/dharlev/From-dysphoria-to-anhedonia-Age-related-shift-in-the-link-between-cognitive-and-affective-symptoms. Ethical approval for the study was granted by the Cambridgeshire 2 Research Ethics Committee (reference: 10/H0308/50), and written informed consent was obtained from all participants prior to their participation. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes The abstract and introduction have been revised to clarify the dimensional and domain-based psychiatric framework underlying the study. These changes emphasize how traditional categorical diagnoses (e.g., major depressive disorder) may obscure the heterogeneity of depressive symptoms across the lifespan. The revised text positions the work within a modern, dimensional approach to psychopathology that examines specific symptom interactions, particularly between affective and cognitive domains, rather than relying on fixed diagnostic categories. No other changes were made to the results or methods. Data and code availability All data used for this work are publicly available upon signing data sharing agreement on https://cam-can.mrc-cbu.cam.ac.uk/dataset/. Code used to analyse the data and generate the figures is available on https://github.com/dharlev/From-dysphoria-to-anhedonia-Age-related-shift-in-the-link-between-cognitive-and-affective-symptoms.