Subtypes of Late-Life Depression: A Data-Driven Approach on Cognitive Domains and Physical Frailty

Abstract

Background With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life-related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance, and physical frailty. Methods A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout, and mortality at 2-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty. Results A latent profile analysis model with five classes best described the data, yielding two subgroups suffering from pure depression (“mild” and “severe” depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labeled as “amnestic depression,” “frail-depressed, physically dominated,” and “frail-depressed, cognitively dominated.” The prospective analyses showed that patients in the subgroup of “mild depression” and “amnestic depression” had the highest remission rates, whereas patients in both frail-depressed subgroups had the highest mortality rates. Conclusions Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according to the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy, and augmentation with geriatric rehabilitation.

Structural and functional neuroimaging of late-life depression: a coordinate-based meta-analysis

“…While more homogenous than MDD in its entirety, LLD also represents a heterogenous diagnostic category. Using clinical variables, five distinct subtypes of LLD, including 'mild pure depression', 'severe pure depression', 'amnestic depression', 'frail-depressed, physically dominated', and 'frail-depressed, cognitively dominated' have been identified, which interestingly correlate with the rate of remission and mortality (Lugtenburg et al, 2020).…”

Longitudinal Association between Late-Life Depression (LLD) and Frailty: Findings from a Prospective Cohort Study (MiMiCS-FRAIL)

“…Evidence from clinical samples is scarce and most are cross-sectional involving either psychiatric outpatients (23,24), renal transplant patients (25), geriatric inpatients (26) or are longitudinal studies in psychogeriatric clinics (19,27,28). Older adults referred to geriatric outpatient clinics are potentially more complex due to higher rates of multimorbidity, frailty and depression compared to community samples (29).…”

Coping strategies of older adults with a recent hip fracture within inpatient geriatric rehabilitation

“…Moreover, current literature on late-life depression demonstrates that depression in older age has a more chronic course, and an increased risk to be treatment resistant (Schaakxs et al, 2018). From a biological perspective, certain factors related to the (neuro)biological aging process such as physical frailty and cognitive decline, may contribute to the development and expression of neuropsychiatric symptoms, and in part explain the impaired prognosis of late-life depression (Lugtenburg et al, 2021). How all these mechanisms relate to each other, is still unknown, and is at present subject to further research (Reynolds, Lenze, & Mulsant, 2019).…”