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Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability
- Maria Kryza-Lacombe, Michelle T. Kassel, Philip S. Insel, Emma Rhodes, David Bickford, Emily Burns, Meryl A. Butters, Duygu Tosun, Paul Aisen, Rema Raman, Susan Landau, Andrew J. Saykin, Arthur W. Toga, Clifford R. Jack, Jr, Robert Koeppe, Michael W. Weiner, Craig Nelson, R. Scott Mackin
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- Journal:
- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 25 January 2024, pp. 1-12
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Objectives:
Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD.
Participants and Measurements:Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity.
Results:Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p = .031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety.
Conclusions:Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.
55 Hoarding Behaviors in Late Life Depression are Associated with Increased Burden of Executive Dysfunction, Disability, and Poorer Response to Depression Treatment
- Michelle T. Kassel, Philip S. Insel, Emma Rhodes, Kai Woodworth, Christina Garrison-Diehn, Derek D. Satre, Duygu Tosun, J. Craig Nelson, Carol A. Mathews, R. Scott Mackin
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 840-841
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Objective:
Late Life Major Depressive Disorder (LLD) and Hoarding Disorder (HD) are common in older adults with prevalence estimates up to 29% and 7%, respectively. Both LLD and HD are characterized by executive dysfunction and disability. There is evidence of overlapping neurobiological dysfunction in LLD and HD suggesting potential for compounded executive dysfunction and disability in the context of comorbid HD and LLD. Yet, prevalence of HD in primary presenting LLD has not been examined and potential compounded impact on executive functioning, disability, and treatment response remains unknown. Thus, the present study aimed to determine the prevalence of co-occurring HD in primary presenting LLD and examine hoarding symptom severity as a contributor to executive dysfunction, disability, and response to treatment for LLD.
Participants and Methods:Eighty-three adults ages 65-90 participating in a psychotherapy study for LLD completed measures of hoarding symptom severity (Savings Inventory-Revised: SI-R), executive functioning (WAIS-IV Digit Span, Letter-Number Sequencing, Coding; Stroop Interference; Trail Making Test-Part B; Letter Fluency), functional ability (World Health Organization Disability Assessment Schedule-II-Short), and depression severity (Hamilton Depression Rating Scale) at post-treatment. Pearson's Chi-squared tests evaluated group differences in cognitive and functional impairment rates and depression treatment response between participants with (HD+LLD) and without (LLD-only) clinically significant hoarding symptoms. Linear regressions were used to examine the association between hoarding symptom severity and executive function performance and functional ability and included as covariates participant age, years of education, gender, and concurrent depression severity.
Results:At post-treatment, 24.1% (20/83) of participants with LLD met criteria for clinically significant hoarding symptoms (SI-R.41). Relative to LLD-only, the LLD+HD group demonstrated greater impairment rates in Letter-Number Sequencing (χ2(1)=4.0, p=.045) and Stroop Interference (χ2(1)=4.8, p=.028). Greater hoarding symptom severity was associated with poorer executive functioning performance on Digit Span (t(71)=-2.4, β=-0.07, p=.019), Letter-Number Sequencing (t(70)=-2.1, β=-0.05, p=.044), and Letter Fluency (t(71)=-2.8, β=-0.24, p=.006). Rates of functional impairment were significantly higher in the LLD+HD (88.0%) group compared to the LLD-only (62.3%) group, (χ2(1)=5.41, p=.020). Additionally, higher hoarding symptom severity was related to greater disability (t(72)=2.97, β=0.13, p=.004). Furthermore, depression treatment response rates were significantly lower in the LLD+HD group at 24.0% (6/25) compared to 48.3% (28/58) in the LLD-only group, χ2(1)=4.26, p=.039.
Conclusions:The present study is among the first to report prevalence of clinically significant hoarding symptoms in primary presenting LLD. The findings of 24.1% co-occurrence of HD in primary presenting LLD and increased burden on executive functioning, disability, and depression treatment outcomes have important implications for intervention and prevention efforts. Hoarding symptoms are likely under-evaluated, and thus may be overlooked, in clinical settings where LLD is identified as the primary diagnosis. Taken together with results indicating poorer depression treatment response in LLD+HD, these findings underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group. Future work examining the course of hoarding symptomatology in LLD (e.g., onset age of hoarding behaviors) may provide insights into the mechanisms associated with greater executive dysfunction and disability.
Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder
- Michelle T. Kassel, Julia A. Rao, Sara J. Walker, Emily M. Briceño, Laura B. Gabriel, Anne L. Weldon, Erich T. Avery, Brennan D. Haase, Marta Peciña, Ciaran M. Considine, Douglas C. Noll, Linas A. Bieliauskas, Monica N. Starkman, Jon-Kar Zubieta, Robert C. Welsh, Bruno Giordani, Sara L. Weisenbach, Scott A. Langenecker
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- Journal:
- Journal of the International Neuropsychological Society / Volume 22 / Issue 4 / April 2016
- Published online by Cambridge University Press:
- 02 February 2016, pp. 412-425
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Objectives: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Methods: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. Results: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Conclusions: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. (JINS, 2016, 22, 412–425)