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4 An Update: Greater Apathy Associated with Selective Serotonin Reuptake Inhibitor Use in Parkinson’s Disease
- Rachel Schade, Lauren Kenney, Alyssa Ray, Lauren Santos, Francesca Lopez, Adrianna Ratajska, Katie Rodriguez
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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. 110-111
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Objective:
Apathy is a primary lack of motivation that is frequently reported in Parkinson’s disease (PD) and often misdiagnosed as depression. In PD, apathy worsens over time with motor symptom progression. Evidence over the past 15 years has documented that use of selective serotonin reuptake inhibitors (SSRIs) is associated with increased apathy in patients with depression, including individuals with PD. In PD, this appears to be related to downregulation of dopaminergic systems by serotonin. Despite increasing evidence, SSRIs continue to be heavily prescribed in individuals with PD— potentially worsening apathy and decreasing quality of life for these individuals. This study is an update, re-examining the relationship between apathy and the use of SSRIs and other antidepressants in a large cohort of individuals with PD.
Participants and Methods:Participants included a convenience sample of 387 nondemented individuals with idiopathic PD who were in their mid-60's (mean age=64.9+8.72 years), well-educated (mean=14.95+2.78 years), predominantly male (72.4%), non-Hispanic white (94.5%), and in mid-stage of disease severity (on medication Unified Parkinson Disease Rating Scale motor score=25.3+10.1). All scored above clinical cutoff for dementia on a cognitive screener (Dementia Rating Scale-2 (DRS) > 125). Medications, cognitive, mood, and clinical data were extracted from chart review. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped into SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs) and other. Analyses included bootstrapped Pearson’s correlations, Pearson’s chi-square, and linear regressions
Results:Among 387 individuals with PD, 41.3% (N=160) were taking antidepressant medications. Of these 160, 61.3% were on SSRIs, 24.4% on SNRIs, and the remainder on other antidepressants. Approximately 36.9% of the 387 PD patients exceeded recommended clinical cutoffs for apathy (AS >14) and 23.5% for depression (BDI-II >14) (Starkstein et al., 1992; Beck et al., 1996). Individuals taking SSRIs (N=98, x2=5.14, p=0.023) or SNRIs (N=39; x2=5.43, p=0.020) were more likely to be clinically apathetic than those taking other depression medications (N=23; x2=1.28, p=0.26). Results of a multiple regression with age, education, disease duration, motor severity, DRS-2, BDI-II, and all psychotropic medications (anti-depressants, anti-anxiety, anti-psychotics) as independent variables explained 42.8% of the variance in total apathy scores (F[17,285]=12.550, p<0.001). SSRIs were the only medication to significantly predict greater AS scores (ß=0.110, p=0.020) in this model. Less education (ß=-0.119, p=0.017) worse cognition (ß=-0.128, p=0.009), and greater depressive symptoms (ß=0.561, p<0.001) were also significant predictors of apathy.
Conclusions:These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy as a potential adverse effect when determining which anti-depressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative anti-depressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study. Longitudinal studies are also needed to elucidate the relationship of apathy and anti-depressant use over time, specifically to determine potential causality of this observed association. Funding: T32-NS082168
5 Anticholinergic Medications, Cognition, and Parkinson’s Disease. Do Medications matter?
- Lauren G Santos, Lauren E Kenney, Alyssa Ray, Alfredo A Paredes, Adrianna M Ratajska, Dawn Bowers
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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. 111-112
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Objective:
While Parkinson’s disease (PD) is traditionally known as a movement disorder, cognitive decline is one of the most debilitating and common non-motor symptoms. Cognitive profiles of individuals with PD are notably heterogeneous (Goldman et al., 2018). While this variability may arise from the disease itself, other factors might play a role. Greater anticholinergic medication use has been linked to worse cognition in those with PD (Fox et al., 2011, Shah et al., 2013). However, past studies on this topic had small sample sizes, limited ranges of disease duration, and only used cognitive screeners. Thus, this study aimed to examine this question within a large, clinical sample, using a more comprehensive neuropsychological battery. We hypothesized that higher anticholinergic medication usage would relate to worse cognitive performance, particularly memory.
Participants and Methods:Participants included 491 nondemented individuals with PD (m=64.7, SD=9.04 years old; education m=15.01, SD=2.79; 71.9% male; 94.3% non-Hispanics white) who underwent a comprehensive neuropsychological assessment at the UF Fixel Institute’s movement disorders program. Medications at the time of the neuropsychological evaluation were identified from chart review and scored based on anticholinergic properties using the Magellan Anticholinergic Risk Scale (Rudolph J.L., et al, 2008); each medication was scored from 0 (no load) to 3 (high load). The neuropsychological battery included measures across 5 cognitive domains: (1) executive function (Trails B, Stroop Interference, Letter Fluency), (2) verbal delayed memory (WMS-III Logical Memory and Hopkin’s Verbal Learning Test-Revised delayed recalls), (3) language (Boston Naming Test-II, Animal Fluency), (4) visuospatial skills (Judgment of Line Orientation, Face Recognition Test), and (5) attention/working memory (WAIS-III Digit Span Forward and Backward). The published normative scores for each task were converted into z-scores and averaged into a domain composite. Due to non-normality of Magellan scores, Spearman correlations examined the relationship between each cognitive domain composite score and Magellan scores.
Results:As predicted, higher Magellan scores were significantly associated with worse memory (r=-0.11, p=0.016), with a small effect size. There were no significant relationships between Magellan scores and the remaining cognitive domains (EF, language, visuospatial, attention).
Conclusions:We found that greater anticholinergic burden was associated with worse performance on memory, but not other neuropsychological domains, in a large cohort of nondemented individuals with PD who underwent comprehensive assessment. This finding corresponds to previous literature in smaller PD cohorts. Though the effect size was low, this finding highlights the importance of monitoring anticholinergic burden in PD patients in order to minimize detrimental effects of medications on memory function. Future work should examine whether greater anticholinergic burden predicts future progression of memory decline.
Acknowledgement: Supported in part by the NIH, T32-NS082168
18 Regional patterns of mitochondrial function using phosphorus magnetic resonance spectroscopy in older adults at-risk for Alzheimer’s disease.
- Francesca V Lopez, Andrew O’Shea, Stacey Alvarez-Alvarado, Adrianna Ratajska, Lauren Kenney, Rachel Schade, Katie Rodriguez, Alyssa Ray, Rebecca O’Connell, Lauren Santos, Emily Van Etten, Hyun Song, Emma Armstrong, Tiffany Gin, Zhiguang Huo, Gene Alexander, Adam J Woods, Dawn Bowers
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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. 331-332
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Objective:
The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.
Participants and Methods:The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.
Results:31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.
Conclusions:Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.
The Community Assessment to Inform Rapid Response (CAIRR): A Novel Qualitative Data Collection and Analytic Process to Facilitate Hyperlocal COVID-19 Emergency Response Operations in New York City
- Madhury Ray, Rachel Dannefer, Jennifer Pierre, Lauren J Shiman, Hannah L Helmy, Shelby R Boyle, Jae Eun M Chang, Alyssa Creighton, Maria A Soto, Jacqlene Moran
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- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 17 / 2023
- Published online by Cambridge University Press:
- 30 May 2022, e180
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All disasters are local but implementing a hyperlocal response in the midst of a public health emergency is challenging. The availability of neighborhood-level qualitative data that are both timely and relevant to evolving objectives and operations is a limiting factor. In 2020, the New York City Department of Health and Mental Hygiene (NYC DOHMH) responded to the COVID-19 emergency using a novel, hyperlocal approach. Key to the implementation of this approach was the creation of the Community Assessment to Inform Rapid Response (CAIRR), a process for rapid collection and analysis of neighborhood-specific, objective-focused, qualitative data to inform tailored response operations. This paper describes the process of developing the CAIRR and its contribution to the NYC DOHMH’s hyperlocal response in order to guide other jurisdictions seeking to employ a hyperlocal approach in future disaster responses.