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52 Open Access, Normative Morphometric Software Indicate Neurodegeneration Associated with Episodic Memory Dysfunction in Amnestic MCI
- Stephanie Fountain-Zaragoza, Olivia Horn, Kathryn E. Thorn, A. Zarina Kraal, Andreana Benitez
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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. 461-462
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Objective:
Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI, and proprietary software can provide normative quantification of regional atrophy. However, proprietary software can be cost-prohibitive for research settings. Thus, we used the freely available software NOrmative Morphometry Image Statistics (NOMIS) which generates normative z-scores of segmented T1-weighted images from FreeSurfer to determine if these scores replicate established patterns of neurodegeneration in the context of amnestic mild cognitive impairment (aMCI), and whether these measures correlate with episodic memory test performance.
Participants and Methods:Patients with aMCI (n = 25) and cognitively normal controls (CN; n = 74) completed brain MRI and two neuropsychological tests of episodic memory (the Rey Auditory Verbal Learning Test and the Wechsler Logical Memory Tests I & II), from which a single composite of normed scores was computed. A subset returned for follow-up (aMCI n = 11, CN n = 52) after ∼15 months and completed the same procedures. T1-weighted images were segmented using FreeSurfer v6.0 and the outputs were submitted to NOMIS to generate normative morphometric estimates for AD-relevant regions (i.e., hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (i.e., cuneus, lingual gyrus, pericalcarine gyrus), controlling for age, sex, head size, scanner manufacturer, and field strength. Baseline data were used to test for differences in ROI volumes and memory between groups and to assess the within-group associations between ROI volumes and memory performance. We also evaluated changes in ROI volumes and memory over the follow-up interval by testing the main effects of time, group, and the group X time interactions. Lastly, we tested whether change in volume was associated with declines in memory.
Results:At baseline, the aMCI group performed 2 SD below the CN group on episodic memory and exhibited smaller volumes in all AD-relevant regions (volumes 0.4 - 1.2 SD below CN group, ps < .041). There were no group differences in control region volumes. Memory performance was associated with volumes of the AD-relevant regions in the aMCI group (average rho = .51) but not with control regions. ROI volumes were not associated with memory in the CN group. At follow-up, the aMCI group continued to perform 2 SD below the CN group on episodic memory tests; however, change of performance over time did not differ between groups. The aMCI group continued to exhibit smaller volumes in all AD-relevant regions than the CN group, with greater declines in hippocampal volume (17% annual decline vs. 8% annual decline) and entorhinal volume (54% annual decline vs. 5% annual decline). There was a trending Group X Time interaction such that decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group but not the CN group.
Conclusions:Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software.
74 A Phase I Trial of Accelerated, HighDose Repetitive Transcranial Magnetic Stimulation to Improve Cognition in Amnestic MCI
- Stephanie Fountain-Zaragoza, James Lopez, Katrina Rbeiz, Holly H Fleischmann, Olivia Horn, Katrina Madden, Michael Antonucci, Gonzalo Revuelta, Lisa M McTeague
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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. 479-480
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Objective:
Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation therapy most widely used in depression, has shown evidence of secondary benefits for cognition in both neurologic and neuropsychiatric conditions. The recent development of more efficient stimulation protocols, such as accelerated high-dose intermittent theta burst (iTBS)-rTMS, has substantially reduced treatment burden by shortening the treatment course by >50%. This study aimed to establish the safety, feasibility, acceptability, and preliminary efficacy of iTBS-rTMS as a tool for bolstering cognition in individuals with amnestic mild cognitive impairment (aMCI).
Participants and Methods:Twenty-four patients with aMCI were enrolled in an open-label phase I trial of iTBS-rTMS; 2 withdrew prior to initiating treatment due to personal circumstances. All participants had received a diagnosis of MCI due to possible AD from a healthcare provider (i.e., neurologist or neuropsychologist) and met actuarial neuropsychological criteria for aMCI. This sample of older adults (range: 61.5-85.2 years, M = 74.1, SD = 5.71) was predominantly White/non-Hispanic (n = 23; Black/non-Hispanic: n = 1), roughly half female (n = 13), with a college education (range: 12-20 years, M = 15.9, SD = 2.5). Participants received 24 sessions of iTBS-rTMS to the left dorsolateral prefrontal cortex over 3 days (8 sessions each, lasting roughly 2 hours per day). Participants rated their perceptions and experience of common side effects during and after each treatment session as well as retrospectively at post-treatment and 4-week follow-up. They completed structural and functional brain MRI, neuropsychiatric evaluations, and neuropsychological assessments before and after treatment and were administered a subset of these measures at 4-week follow-up. MoCA scores were used to monitor for adverse neurocognitive effects, and the fluid cognition composite score from the NIH Toolbox Cognition Battery was used to test preliminary efficacy.
Results:We achieved a high retention rate (95%), with 21 of the 22 participants completing all study procedures. There were no clinically significant adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participant reports indicated high tolerability and acceptability, with a modal rating of 0 (on a scale from 0=not at all to 10=extremely) for six common side effects (i.e., headache, pain, scalp irritation, facial twitching, fatigue, fear/anxiety), assessed both during and after each treatment session. They reported very low desire to quit despite some participants rating the treatment as moderately tiring. We observed significant, large effect-size (d = 0.98) improvements in fluid cognition from pre- to post-treatment.
Conclusions:Our findings support the safety, feasibility, and acceptability of iTBS-rTMS treatment in patients with aMCI. Further, although not explicitly dosed for efficacy, we provide preliminary evidence of improved fluid cognition as a function of treatment, highlighting the potential of this treatment for improving trans-domain cognitive impairment. These promising results can directly inform future trials aimed at optimizing treatment parameters, broadening the indication to other MCI subtypes, and testing the augmentation of established cognitive rehabilitation interventions when combined with rTMS.
Aging and Attentional Control: Examining the Roles of Mind-Wandering Propensity and Dispositional Mindfulness
- Stephanie Fountain-Zaragoza, Nicole A. Puccetti, Patrick Whitmoyer, Ruchika Shaurya Prakash
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 8 / September 2018
- Published online by Cambridge University Press:
- 29 August 2018, pp. 876-888
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Objectives: Aging is associated with declines in performance on certain laboratory tasks of attentional control. However, older adults tend to report greater mindful, present-moment attention and less mind-wandering (MW) than young adults. For older adults, high levels of these traits may be protective for attentional performance. This study examined age-related differences in global (i.e., full-task) and local (i.e., pre-MW) attentional control and explored the variance explained by MW and mindfulness. Methods: Cross-sectional comparisons were conducted on data from a previously reported sample of 75 older adults (ages, 60–75 years) and a new sample of 50 young adults (ages, 18–30 years). All participants completed a Go/No-Go task and a Continuous Performance Task with quasi-random MW probes. Results: There were few age-related differences in attentional control. Although MW was not associated with decrements in global performance, local performance measures revealed deleterious effects of MW, which were present across age groups. Older adults reported higher trait mindfulness and less MW than young adults, and these variables helped explain the lack of observed age-related differences in attentional control. Conclusions: Individual differences in dispositional mindfulness and MW propensity explain important variance in attentional performance across age. Increasing present-moment focus and reducing lapses in attention represent important targets for cognitive rehabilitation interventions. (JINS, 2018, 24, 876–888)