Abstract
Introduction Prior literature has proposed that the co-existence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. Methods English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, fifteen studies including 11,213 participants met criteria for inclusion in this study. Results The triad's existence was supported by 12 of the 15 studies (80%), including four longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacological and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities (WMH) and the triad, with one study finding a significant longitudinal relationship with periventricular WMH. Vascular risk factors were also commonly associated with this triad. Conclusions Taken together, the relationship between this triad, the vascular depression hypothesis and frontal subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this triad. This research was funded by: There are no sources of funding for the article. Prior literature has proposed that the co-existence of late-life depression, executive dysfunction and impaired gait speed may constitute a specific phenotype in older adults with a possible shared brain mechanism. All three conditions are independently associated with negative health outcomes including impaired function, risk of falling and reduced quality of life. However, the existence, etiology, and implications of having all three conditions as a unitary triad remain unclear. This systematic review examined the literature to assess the consistency of this triad and to explore the possible role of frontal-subcortical circuitry in its etiology. English language literature that assessed mood, executive function, and gait speed using a validated tool in human participants over age 65 were included for this review. Following the PRISMA guidelines, fifteen studies including 11,213 participants met criteria for inclusion in this study. The triad's existence was supported by 12 of the 15 studies (80%), including four longitudinal studies involving 368 participants. A prevalence of 17% was reported in one population study. The three included intervention studies provided mixed results regarding the benefit of pharmacological and exercise interventions. Two studies assessed the association between presence of white matter hyperintensities (WMH) and the triad, with one study finding a significant longitudinal relationship with periventricular WMH. Vascular risk factors were also commonly associated with this triad. Taken together, the relationship between this triad, the vascular depression hypothesis and frontal subcortical pathology is suggested. Further longitudinal research is needed to further clarify the etiology and clinical relevance of this triad.
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