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22 Cognitive Reserve's Relationship to Brain Burden in Parkinson's Disease Without Dementia
- Lauren E. Kenney, Jared Tanner, Samuel J. Crowley, Thomas H. Mareci, Francesca V. Lopez, Adrianna M. Ratajska, Katie Rodriguez, Rachel Schade, Joshua Gertler, Catherine C. Price, 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. 539-540
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Objective:
Individuals with Parkinson's disease (PD) have varying trajectories of cognitive decline. One reason for this heterogeneity may be "cognitive reserve": where higher education/IQ/current mental engagement compensates for increasing brain burden (Stern et al., 2020). With few exceptions, most studies examining cognitive reserve in PD fail to include brain metrics. This study's goal was to examine whether cognitive reserve moderated the relationship between neuroimaging indices of brain burden (diffusion free water fraction and T2-weighted white matter changes) and two commonly impaired domains in PD: executive function and memory. We hypothesized cognitive reserve would mitigate the relationship between higher brain burden and worse cognitive performance.
Participants and Methods:Participants included 108 individuals with PD without dementia (age mean=67.9±6.3, education mean=16.6±2.5) who were prospectively recruited for two NIH-funded projects at the University of Florida. All received neuropsychological measures of executive function (Trails B, Stroop, Letter Fluency) and memory (delayed recall: Hopkin's Verbal Learning Test-Revised, WMS-III Logical Memory). Domain specific z-score composites were created using data from age/education matched non-PD peer controls (N=62). For the Cognitive Reserve (CR) proxy, a z-score composite included years of education, WASI-II Vocabulary, and Wechsler Test of Adult Reading. At the time of testing, participants completed multiple MRI scans (T1-weighted, diffusion, Fluid Attenuated Inversion Recovery) from which the following were extracted: 1) whole-brain free water within the white matter (a measure of microstructural integrity and neuroinflammation), 2) white matter hyperintensities/white matter total volume (WMH/WMV), and bilaterally-averaged edge weights of white matter connectivity between 3) dorsolateral prefrontal cortex and caudate and 4) entorhinal cortex and hippocampi. Separate linear regressions for each brain metric used executive function and memory composites as dependent variables; predictors were age, CR proxy, respective brain metric, and a residual centered interaction term (brain metric*CR proxy). Identical models were run in dichotomized short and long disease duration groups (median split=6 years).
Results:In all models, a lower CR proxy significantly predicted worse executive function (WMH/WMV: beta=0.49, free water: beta=0.54, frontal edge weight: beta=0.49, p's<0.001) and memory (WMH/WMV: beta=0.42, free water: beta=0.35, temporal edge weight: beta=0.39, p's <0.01). For neuroimaging metrics, higher free water significantly predicted worse executive function (beta=-0.39, p=0.002) but not memory. No other brain metrics were significant predictors of either domain. Accounting for PD duration, higher free water predicted worse executive function for those with both short (beta=-0.49, p=0.04) and long disease duration (beta=-0.48, p=0.02). Specifically in those with long disease duration, higher free water (beta=-0.57 p=0.02) and lower edge weights between entorhinal cortex and hippocampi (beta=0.30, p=0.03) predicted worse memory. Overall, no models contained significant interactions between the CR proxy and any brain metric.
Conclusions:Results replicate previous work showing that a cognitive reserve proxy relates to cognition. However, cognitive reserve did not moderate brain burden's relationship to cognition. Across the sample, greater neuroinflammation was associated with worse executive function. For those with longer disease duration, higher neuroinflammation and lower medial temporal white matter connectivity related to worse memory. Future work should examine other brain burden metrics to determine whether/how cognitive reserve influences the cognitive trajectory of PD.
3 The Relationship Between Depression, Anxiety, and Autonomic Dysfunction in de novo Parkinson’s Disease Patients Over Time
- Adrianna M. Ratajska, Francesca V. Lopez, Lauren E. Kenney, Katie Rodriguez, Rachel Schade, Joshua Gertler, 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. 109-110
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Objective:
Autonomic dysfunction is an important non-motor symptom of Parkinson’s disease (PD), with point prevalence estimates of approximately 50-70%. Common presentations include cardiovascular dysregulation, gastrointestinal dysfunction, impaired thermoregulation, and sexual dysfunction. In the present study, we sought to examine whether autonomic symptoms would predict trajectories of change in depression and anxiety over a 5-year period in newly diagnosed individuals with PD. Given that alterations in autonomic nervous system functioning (e.g., reduced heart rate variability, lower autonomic arousal) are frequently observed in individuals who have anxiety and depression, as well as the negative influence these symptoms can have on quality of life/functioning, we predicted that greater autonomic symptoms would be related to increased mood symptoms over time.
Participants and Methods:Participants included 414 individuals from the Parkinson’s Progression Markers Initiative, a prospective study of newly diagnosed and untreated individuals with PD. The PD participants (mean age=61.6+9.7, mean education=15.6+3.0, 92.5% non-Hispanic White) were followed annually for up to five years. Self-reported autonomic symptoms were measured using the Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction (SCOPA-AUT), which consists of a total score and 6 subdomain scores (gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, sexual). Mood measures included the Geriatric Depression Scale (GDS) and State-Trait Anxiety Inventory (STAI). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III. Bootstrapped linear regressions were performed to evaluate the relationship between autonomic symptoms (subdomains) and mood using data from the last visit (year 5). For longitudinal analyses, bootstrapped multilevel modeling was used to examine a) changes in SCOPA-AUT total over time (unconditional growth model only) and b) the relationship between mood and SCOPA-AUT total score over time, controlling for age/sex and motor severity.
Results:Autonomic symptoms explained 28.2% of the total variance in trait anxiety, with unique predictors of gastrointestinal (/3=.266, p<.001) and thermoregulatory (ß=.202, p=.004) symptoms. For depression, autonomic symptoms explained 27.9% of the total variance, with unique predictors of gastrointestinal (ß=.225, p=.012), thermoregulatory (ß=.178, p=.013), and cardiovascular (ß=.154, p=.012) symptoms. There was a gradual linear increase in total autonomic symptoms over time (b=0.86, p<.001). Greater total autonomic symptoms were associated with higher average trait anxiety (b=0.54, p<.001), slightly greater increase in trait anxiety over time (b=0.04, p<.05), and occasion-to-occasion fluctuations in trait anxiety (b=0.24, p<.001). Similarly, increased total autonomic symptoms were associated with higher average depressive symptoms (b=0.14, p<.001), minimally greater increase in depressive symptoms over time (b=0.01, p<.05), and occasion-to-occasion fluctuations in depressive symptoms (b=0.08, p<.001). Motor severity did not explain individual differences or trajectories of change in depression or trait anxiety.
Conclusions:Autonomic symptoms, particularly gastrointestinal, cardiovascular, and thermoregulatory dysfunction, were related to increased mood symptoms in PD patients and predicted increases in depression/anxiety over time. Our findings do not distinguish between two theoretical possibilities - whether autonomic symptoms lead to depression/anxiety versus involvement of co-occurring neural systems underlying both. Regardless, our study highlights the importance of treating autonomic dysfunction in early PD, and future work should incorporate additional measures of autonomic dysfunction (e.g., physiological probes).
20 Laterality of Motor Symptom Onset is Not Associated with Cognitive Performance or Mood Symptoms in a Sample of 600 Individuals with Idiopathic Parkinson’s Disease”
- Joshua Gertler, Lauren Kenney, Adrianna M Ratajska, Francesca V Lopez, Katie Rodriguez, Rachel Schade, 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. 537-538
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Objective:
Parkinson’s disease (PD) is typically characterized by unilateral onset of motor symptoms (i.e., tremors, rigidity) which is caused by dopaminergic degeneration of the substantia nigra that influences basal ganglia-prefrontal circuitry. Over time, motor symptoms become more bilateral, though continue to remain asymmetric. Many neuropsychological studies suggest that laterality of motor onset may be linked to hemispheric specific cognitive or mood changes. Namely, worse verbal/language performance may be present in individuals with right body (left hemisphere) onset and conversely for visuospatial performance, with depression symptoms relating more so to individuals with right body (left hemisphere) onset. To date, findings are often inconsistent, with some studies showing evidence for laterality effects and others not. The basis for this inconsistency is unclear, though one possibility relates to small sample sizes and varying methodologies. Thus, the goal of this study was to examine potential cognitive and mood laterality effects in a large clinical sample of individuals with PD.
Participants and Methods:Participants included a convenience sample of 600 nondemented individuals with idiopathic PD from the University of Florida Fixel Institute Movement Disorders Center. As a group, participants were around 60 years of age (Mean Age=63.9+9.4), well educated (Mean years=14.9+2.7), predominantly male (70%), and white non-Hispanic (93%). Side of initial motor symptom onset was based on self-report: Right (N=337) and Left (N=263). Approximately 79% were tremor predominant. All received mood and neurocognitive measures as part of standard clinical care, including indices of executive function (Stroop Color-Word, Trails B, Letter Fluency), recent verbal memory (delayed recall: Hopkin’s Verbal Learning Test, WMS-III Logical Memory), language (Boston Naming Test, Animal fluency), visuospatial skills (Judgment of Line Orientation, Facial Recognition Test). Evaluation of emotion symptoms included: depression (Beck Depression Inventory-II), apathy (Apathy Scale), and anxiety (State-Trait Anxiety Inventory). Analyses used raw scores from these measures. Due to non-normality of most measures’ distributions, laterality effects were examined using bootstrapped multivariate methods (multivariate analysis of variance [MANOVA]). Separate MANOVA’s were run for each cognitive domain (i.e., EF, language, etc.) and mood measures.
Results:The right and left sided onset groups did not significantly differ in demographic (age, education, sex) or disease characteristics (duration, PD subtype). Results of the MANOVA’s with cognitive variables were all nonsignificant broadly (all with F’s ranging from .33 to .94) and at the single test level. Similarly, the left and right onset groups did not significantly differ (a=0.05) across standard scales of depression (F=0.031), anxiety (Trait F=0.463; State F=3.29), and apathy (F=0.74).
Conclusions:We found no evidence that laterality of initial motor symptoms influenced cognitive or mood symptoms in a large cohort of 600 individuals with PD. These findings raise questions about importance of motor onset laterality for cognitive and emotion related changes in PD. Future studies should move beyond self-report and behavioral motor scales for determining hemispheric contributions. In PD, use of refined metrics for determining the extent of asymmetric dopaminergic degeneration (e.g., DAT scan) at the hemispheric level coupled with sensitive neuropsychological measures may provide clearer understanding of potential neural circuitry relationships.
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
Perception of cognitive change by individuals with Parkinson’s disease or essential tremor seeking deep brain stimulation: Utility of the cognitive change index
- Katie Rodriguez, Rachel N. Schade, Francesca V. Lopez, Lauren E. Kenney, Adrianna M. Ratajska, Joshua Gertler, Dawn Bowers
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 4 / May 2024
- Published online by Cambridge University Press:
- 06 October 2023, pp. 370-379
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Objective:
The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson’s disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS).
Methods:216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms.
Results:PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated (m = 15.01 ± 2.92), in their mid-60’s (m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints.
Conclusion:Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.