Browsing by Author "Nelson, Craig"

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    The Impact of Amyloid Burden and APOE on Rates of Cognitive Impairment in Late Life Depression
    (IOS Press, 2021) Rhodes, Emma; Insel, Philip S.; Butters, Meryl A.; Morin, Ruth; Bickford, David; Tosun, Duygu; Gessert, Devon; Rosen, Howie J.; Aisen, Paul; Raman, Rema; Landau, Susan; Saykin, Andrew; Toga, Arthur; Jack, Clifford R.; Weiner, Michael W.; Nelson, Craig; Mackin, R. Scott; Alzheimer’s Disease Neuroimaging Initiative; ADNI Depression Project; Radiology and Imaging Sciences, School of Medicine
    Background: Cognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear. Objective: To evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden. Methods: Participants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden. Results: LLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOEɛ4 genotype was associated with worse performance on Logical Memory I (p = 0.022); these relationships did not differ between LLD and ND. Conclusion: LLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.
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    Late Life Depression is Associated with Reduced Cortical Amyloid Burden: Findings from the ADNI Depression Project
    (Elsevier, 2021) Mackin, R. Scott; Insel, Philip S.; Landau, Susan; Bickford, David; Morin, Ruth; Rhodes, Emma; Tosun, Duygu; Rosen, Howie J.; Butters, Meryl; Aisen, Paul; Raman, Rema; Saykin, Andrew; Toga, Arthur; Jack, Clifford, Jr.; Koeppe, Robert; Weiner, Michael W.; Nelson, Craig; Alzheimer’s Disease Neuroimaging Initiative & the ADNI Depression Project; Radiology and Imaging Sciences, School of Medicine
    Background: We evaluated the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late-life depression (LLD). Methods: A total of 119 older adult participants with a current diagnosis of major depression (LLD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Depression Project study and 119 nondepressed (ND) cognitively unimpaired participants matched on age, sex, and APOE genotype were obtained from the ADNI database. Results: Thirty-three percent of LLD participants met ADNI criteria for mild cognitive impairment. Compared with ND individuals, the LLD group exhibited less global amyloid beta (Aβ) accumulation (p = .05). The proportion of amyloid positivity in the LLD group was 19.3% compared with 31.1% for the ND participants (p = .02). Among LLD participants, global Aβ was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime selective serotonin reuptake inhibitor use, or lifetime length of untreated depression (p > .21 for all). Global Aβ was associated with worse memory performance (p = .05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants as well as when comparing the LLD group with an ND group that included participants with mild cognitive impairment. Conclusions: Contrary to expectation, the LLD group showed less Aβ deposition than the ND group and Aβ deposition was not associated with depression history characteristics. Aβ was associated with memory, but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of LLD are not due to greater cortical Aβ accumulation.
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    Relationship of Hoarding and Depression Symptoms in Older Adults
    (Elsevier, 2024) Nutley, Sara; Nguyen, Binh K.; Mackin, R. Scott; Insel, Philip S.; Tosun, Duygu; Butters, Meryl; Aisen, Paul; Raman, Rema; Saykin, Andrew J.; Toga, Arthur W.; Jack, Clifford; Weiner, Michael W.; Nelson, Craig; Kassel, Michelle; Kryza-Lacombe, Maria; Eichenbaum, Joseph; Nosheny, Rachel L.; Mathews, Carol A.; Radiology and Imaging Sciences, School of Medicine
    Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype. We determined the incidence of HD in two separate cohorts of participants with LLD (n = 73) or lifetime history of MDD (n = 580) and examined the reliability and stability of hoarding symptoms using the Saving Inventory-Revised (SI-R) and Hoarding Rating Scale-Self Report (HRS), as well as the co-variance of hoarding and depression scores over time. HD was present in 12% to 33% of participants with MDD, with higher rates found in those with active depressive symptoms. Hoarding severity was stable across timepoints in both samples (all correlations >0.75), and fewer than 30% of participants in each sample experienced significant changes in severity between any two timepoints. Change in depression symptoms over time did not co-vary with change in hoarding symptoms. These findings indicate that hoarding is a more common comorbidity in LLD than previously suggested, and should be considered in screening and management of LLD. Future studies should further characterize the interaction of these conditions and their impact on outcomes, particularly functional impairment in this vulnerable population.