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58 Hippocampal Subregions Predict Executive Function Across the Adult Lifespan
- Zachary N Salling, Sarah M Szymkowicz, Vonetta M Dotson
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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. 466-467
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Objective:
Executive function is known to decline in later life, largely attributed to structural and functional changes in the prefrontal cortex. However, other regions of the brain are integral to executive functioning, including the hippocampus. The hippocampus plays a large role in memory but its intricate connections to limbic regions including the prefrontal cortex likely underlies associations between the hippocampus and executive functions. Due to the hippocampus’ complex structure, hippocampal subregions may be differentially associated with executive function, but this possibility remains largely unexplored. Therefore, we examined the association between volume of the hippocampus and its subregions with executive function to understand these relationships across the adult lifespan.
Participants and Methods:The study included 32 healthy, community-dwelling participants (age range = 18-81, mean age = 51.06 ± 20.98, 91% white, 72% female) who received a 3-Tesla magnetic resonance imaging (MRI) scan and completed a cognitive battery. We calculated an executive composite based on Trail Making Test Part B and the interference score from the Stroop Color and Word Test. Freesurfer (version 5.3) as used to quantify total hippocampal volume and subfield volumes for CA1, CA2-3, CA4-dentate gyrus, subiculum, and presubiculum. We conducted mixed-effects regression analyses with total hippocampal and subfield volume, age group (young, middle-aged, and older), and their interaction predicting the executive function composite, controlling for total intracranial volume.
Results:Larger hippocampal subregion volumes in CA1 (p = 0.03), the subiculum (p = 0.01), and the CA4-dentate gyrus (p = 0.04) predicted better executive function. Total hippocampal volume and the presubiculum were not significantly associated with the executive function composite. The age group interaction was not significant for any of the models. Follow-up analyses by hemisphere showed that the effects were right lateralized in CA1and CA4-dentate gyrus, and bilateral in the subiculum.
Conclusions:These data support the literature demonstrating the involvement of the hippocampus in executive function and demonstrates variation across hippocampal subfields. The lack of significant age interactions suggests these relationships may not differ across the lifespan, although this finding would need to be replicated in larger samples. These findings support previous literature showing CA4-dentate gyrus’ association with neurogenesis may facilitate better executive function by increasing connection strength among CA1, CA2-3, and the frontal cortex. This study contributes to our understanding of how specific hippocampal subregions relate to executive function, which has both clinical and research implications.
72 Cognitive Training Paired with Bifrontal tDCS Decreases Depressive Symptoms in a Non-Clinical Sample of Older Adults: Preliminary Evidence
- Sarah M Szymkowicz, Warren D Taylor, Adam J Woods
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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. 477-478
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Objective:
Subthreshold depressive symptoms are both prevalent and associated with negative outcomes in older adults, including conversion to major depressive disorder and other medical conditions. Antidepressants are not recommended as first-line or sole intervention for subthreshold depression; thus, finding other efficacious interventions is important. In depressed adults, transcranial direct current stimulation (tDCS) applied to the frontal lobe has antidepressant properties and pairing tDCS with cognitive training results in additional benefit due to enhancement of frontal cortical activity. However, these studies have primarily targeted depressed adults under age 65 years and less is known about whether this intervention combination is beneficial or affects subthreshold depressive symptoms in older adults.
Participants and Methods:We are reporting secondary data analyses from Nissim et al. (2019), who recruited 30 non-demented healthy older adults and randomized them to receive active or sham tDCS in combination with cognitive training for 2 weeks. Active tDCS was delivered bifrontally over F3 (cathode) and F4 (anode) for 20-min at 2 mA intensity through two 5x7 cm2 saline saturated sponge electrodes using the Soterix Medical 1x1 tDCS clinical trials device. Sham tDCS had identical set-up with 2 mA stimulation for 30-sec with 30-sec ramp up and down. Cognitive training was administered for 40-min daily using attention/processing speed and working memory modules from BrainHQ. The first 20-min of cognitive training was paired with active or sham tDCS. To allow room for symptom improvement, we only included participants with Beck Depression Inventory, 2nd edition (BDI-II) scores of 5 or greater ("minimal" depression severity). We identified 15 participants who met this cut-off (70.93 ± 5.41 years old, 10 females, 16.4 years ± 2.32 years education, MoCA = 27.27 ± 2.34; 7 active, 8 sham).
Results:tDCS conditions did not significantly differ in age, sex, years of education, MoCA scores, number of completed intervention days, or baseline BDI-II (active: 7.71 ± 2.93, sham: 11.38 ± 6.44). There were no differences in sensation ratings between groups or in confidence ratings for condition received (suggesting successful blinding). Results indicated the combination of active (and not sham) tDCS with cognitive training was associated with reduced depressive symptoms (2.7 vs. 1.4 points, active vs. sham). Including covariates (age, sex, education, MoCA scores, and number of completed intervention days) in the model further strengthened this discrepancy (3.7 vs. 0.51 points, active vs. sham).
Conclusions:While preliminary, these results suggest this intervention combination may be a potential method for improving subthreshold depressive symptoms in older adults via targeting prefrontal neural circuitry and promoting neuroplasticity of the underlying neural network. While baseline BDI-II scores did not significantly differ, the active tDCS group had a lower score than sham, but saw greater improvement in BDI-II scores post-intervention despite having less room for change. Adequate treatment of subthreshold depressive symptoms may prevent or reduce negative outcomes associated with depressive symptoms in at-risk older adults. Larger randomized clinical trials are needed to better understand tDCS plus cognitive training antidepressant effects in this age group.
Influences of resting-state intrinsic functional brain connectivity on the antidepressant treatment response in late-life depression
- Ryan Ahmed, Brian D. Boyd, Damian Elson, Kimberly Albert, Patrick Begnoche, Hakmook Kang, Bennett A. Landman, Sarah M. Szymkowicz, Patricia Andrews, Jennifer Vega, Warren D. Taylor
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- Journal:
- Psychological Medicine / Volume 53 / Issue 13 / October 2023
- Published online by Cambridge University Press:
- 09 December 2022, pp. 6261-6270
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Background
Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.
MethodsParticipants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.
ResultsIn primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.
ConclusionsResponse to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.
RegistrationClinicalTrials.gov NCT02332291
Cognitive phenotypes in late-life depression
- Sarah M. Szymkowicz, Claire Ryan, Damian M. Elson, Hakmook Kang, Warren D. Taylor
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue 4 / April 2023
- Published online by Cambridge University Press:
- 29 June 2022, pp. 193-205
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Objective:
To identify cognitive phenotypes in late-life depression (LLD) and describe relationships with sociodemographic and clinical characteristics.
Design:Observational cohort study
Setting:Baseline data from participants recruited via clinical referrals and community advertisements who enrolled in two separate studies.
Participants:Non-demented adults with LLD (n = 120; mean age = 66.73 ± 5.35 years) and non-depressed elders (n = 56; mean age = 67.95 ± 6.34 years).
Measurements:All completed a neuropsychological battery, and individual cognitive test scores were standardized across the entire sample without correcting for demographics. Five empirically derived cognitive domain composites were created, and cluster analytic approaches (hierarchical, k-means) were independently conducted to classify cognitive patterns in the depressed cohort only. Baseline sociodemographic and clinical characteristics were then compared across groups.
Results:A three-cluster solution best reflected the data, including “High Normal” (n = 47), “Reduced Normal” (n = 35), and “Low Executive Function” (n = 37) groups. The “High Normal” group was younger, more educated, predominantly Caucasian, and had fewer vascular risk factors and higher Mini-Mental Status Examination compared to “Low Executive Function” group. No differences were observed on other sociodemographic or clinical characteristics. Exploration of the “High Normal” group found two subgroups that only differed in attention/working memory performance and length of the current depressive episode.
Conclusions:Three cognitive phenotypes in LLD were identified that slightly differed in sociodemographic and disease-specific variables, but not in the quality of specific symptoms reported. Future work on these cognitive phenotypes will examine relationships to treatment response, vulnerability to cognitive decline, and neuroimaging markers to help disentangle the heterogeneity seen in this patient population
Symptom Dimensions of Depression and Apathy and Their Relationship With Cognition in Parkinson’s Disease
- Sarah M. Szymkowicz, Vonetta M. Dotson, Jacob D. Jones, Michael S. Okun, Dawn Bowers
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 3 / March 2018
- Published online by Cambridge University Press:
- 16 October 2017, pp. 269-282
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Objectives: Both depression and apathy, alone and in combination, have been shown to negatively affect cognition in patients with Parkinson’s disease (PD). However, the influence of specific symptom dimensions of depression and apathy on cognition is not well understood. The current study investigated the relationship between symptom dimensions of depression and apathy, based on factors identified in Kirsch-Darrow et al. (2011), and memory and executive function in PD. Methods: A sample of 138 non-demented individuals with PD (mean age=64.51±7.43 years) underwent neuropsychological testing and completed the Beck Depression Inventory, 2nd Edition, and Apathy Scale. Separate hierarchical regression models examined the relationship between symptom dimensions of depression and apathy (“pure” depressive symptoms, “pure” apathy, loss of interest/pleasure [anhedonia], and somatic symptoms) and three cognitive domain composites: immediate verbal memory, delayed verbal memory, and executive function. Results: After adjusting for general cognitive status and the influence of the other symptom dimensions, “pure” depressive symptoms were negatively associated with the delayed verbal memory composite (p<.034) and somatic symptoms were positively associated with the executive function composite (p<.026). No symptom dimensions were significantly related to the immediate verbal memory composite. Conclusions: Findings suggest that specific mood symptoms are associated with delayed verbal memory and executive function performance in non-demented patients with PD. Further research is needed to better understand possible mechanisms through which specific symptom dimensions of depression and apathy are associated with cognition in PD. (JINS, 2018, 24, 269–282)