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Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL).

ABSTRACT: OBJECTIVE:To discuss the design, rationale, and implementation of an intervention development study addressing indicated and selective prevention of depression and anxiety in individuals 60 years and older with mild cognitive impairment (MCI) and in their caregivers. METHODS:In Phase I, now completed, we developed and standardized problem-solving therapy (PST) and the combined PST?+?moderate-intensity physical exercise (PE) intervention to be administered to participants with MCI and their caregivers together, dyadically, with both participants working with the same interventionist in the same therapy sessions. In Phase II we have been testing the interventions against enhanced usual care (EUC) and have addressed challenges to recruitment. Randomization was to one of three cells: PST?+?PE, PST, or EUC. RESULTS:Although we set out to intervene dyadically, many individuals with MCI lived alone or did not have a support person who could participate in the study with them. Consequently, we modified the study to include MCI participants with and without support persons. Ninety-four participants were enrolled: 20 with MCI together with their support persons (N?=?20 dyads) and 54 MCI participants without accompanying support persons. Most participants have been satisfied with the usefulness of the interventions in managing stress and cognitive problems. CONCLUSION:PST and moderate-intensity PE are acceptable interventions for depression and anxiety prevention in older adults with MCI and their available caregivers.

SUBMITTER: Gildengers AG

PROVIDER: S-EPMC4871778 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL).

Gildengers Ariel G AG Butters Meryl A MA Albert Steven M SM Anderson Stewart J SJ Dew Mary Amanda MA Erickson Kirk K Garand Linda L Karp Jordan F JF Lockovich Michael H MH Morse Jennifer J Reynolds Charles F CF

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20151118 6

<h4>Objective</h4>To discuss the design, rationale, and implementation of an intervention development study addressing indicated and selective prevention of depression and anxiety in individuals 60 years and older with mild cognitive impairment (MCI) and in their caregivers.<h4>Methods</h4>In Phase I, now completed, we developed and standardized problem-solving therapy (PST) and the combined PST + moderate-intensity physical exercise (PE) intervention to be administered to participants with MCI ...[more]

PMID: 27066730

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Project description:ImportanceLate-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity might aid in elucidating etiological mechanisms and support precision and individualized medicine.ObjectiveTo cross-sectionally and longitudinally delineate disease-related heterogeneity in LLD associated with neuroanatomy, cognitive functioning, clinical symptoms, and genetic profiles.Design, setting, and participantsThe Imaging-Based Coordinate System for Aging and Neurodegenerative Diseases (iSTAGING) study is an international multicenter consortium investigating brain aging in pooled and harmonized data from 13 studies with more than 35 000 participants, including a subset of individuals with major depressive disorder. Multimodal data from a multicenter sample (N = 996), including neuroimaging, neurocognitive assessments, and genetics, were analyzed in this study. A semisupervised clustering method (heterogeneity through discriminative analysis) was applied to regional gray matter (GM) brain volumes to derive dimensional representations. Data were collected from July 2017 to July 2020 and analyzed from July 2020 to December 2021.Main outcomes and measuresTwo dimensions were identified to delineate LLD-associated heterogeneity in voxelwise GM maps, white matter (WM) fractional anisotropy, neurocognitive functioning, clinical phenotype, and genetics.ResultsA total of 501 participants with LLD (mean [SD] age, 67.39 [5.56] years; 332 women) and 495 healthy control individuals (mean [SD] age, 66.53 [5.16] years; 333 women) were included. Patients in dimension 1 demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy control individuals. In contrast, patients in dimension 2 showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, 1 de novo independent genetic variant (rs13120336; chromosome: 4, 186387714; minor allele, G) was significantly associated with dimension 1 (odds ratio, 2.35; SE, 0.15; P = 3.14 ×108) but not with dimension 2. The 2 dimensions demonstrated significant single-nucleotide variant-based heritability of 18% to 27% within the general population (N = 12 518 in UK Biobank). In a subset of individuals having longitudinal measurements, those in dimension 2 experienced a more rapid longitudinal change in GM and brain age (Cohen f2 = 0.03; P = .02) and were more likely to progress to Alzheimer disease (Cohen f2 = 0.03; P = .03) compared with those in dimension 1 (N = 1431 participants and 7224 scans from the Alzheimer's Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], and Biomarkers for Older Controls at Risk for Dementia [BIOCARD] data sets).Conclusions and relevanceThis study characterized heterogeneity in LLD into 2 dimensions with distinct neuroanatomical, cognitive, clinical, and genetic profiles. This dimensional approach provides a potential mechanism for investigating the heterogeneity of LLD and the relevance of the latent dimensions to possible disease mechanisms, clinical outcomes, and responses to interventions.

Project description:Late-life depression (LLD), compared to depression at a young age, is more likely to have poor prognosis and high risk of progression to dementia. A recent systemic review and meta-analysis of the present antidepressants for LLD showed that the treatment response rate was 48% and the remission rate was only 33.7%, thus implying the need to improve the treatment with other approaches in the future. Recently, agents modulating the glutamatergic system have been tested for mental disorders such as schizophrenia, dementia, and depressive disorder. Ketamine, a noncompetitive NMDA receptor (NMDAR) antagonist, requires more evidence from randomized clinical trials (RCTs) to prove its efficacy and safety in treating LLD. The metabotropic receptors (mGluRs) of the glutamatergic system are family G-protein-coupled receptors, and inhibition of the Group II mGluRs subtypes (mGlu2 and mGlu3) was found to be as effective as ketamine in exerting rapid antidepressant activity in some animal studies. Inflammation has been thought to contribute to depression for a long time. The cytokine levels not only increase with age but also decrease serotonin. Regarding LLD, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) released in vivo are likely to contribute to the reduced serotonin level. Brain-derived neurotrophic factor (BDNF), a growth factor and a modulator in the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors, probably declines quantitatively with age. Recent studies suggest that BDNF/TrkB decrement may contribute to learning deficits and memory impairment. In the process of aging, physiological changes in combination with geriatric diseases such as vascular diseases result in poorer prognosis of LLD in comparison with that of young-age depression. Treatments with present antidepressants have been generally unsatisfactory. Novel treatments such as anti-inflammatory agents or NMDAR agonists/antagonists require more studies in LLD. Last but not least, LLD and dementia, which share common pathways and interrelate reciprocally, are a great concern. If it is possible to enhance the treatment of LDD, dementia can be prevented or delated.

Dataset Information

Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL).

Publications

Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL).

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