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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.
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.
Clarifying status of DNNs as models of human vision
- Jeffrey S. Bowers, Gaurav Malhotra, Marin Dujmović, Milton L. Montero, Christian Tsvetkov, Valerio Biscione, Guillermo Puebla, Federico Adolfi, John E. Hummel, Rachel F. Heaton, Benjamin D. Evans, Jeffrey Mitchell, Ryan Blything
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- Behavioral and Brain Sciences / Volume 46 / 2023
- Published online by Cambridge University Press:
- 06 December 2023, e415
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On several key issues we agree with the commentators. Perhaps most importantly, everyone seems to agree that psychology has an important role to play in building better models of human vision, and (most) everyone agrees (including us) that deep neural networks (DNNs) will play an important role in modelling human vision going forward. But there are also disagreements about what models are for, how DNN–human correspondences should be evaluated, the value of alternative modelling approaches, and impact of marketing hype in the literature. In our view, these latter issues are contributing to many unjustified claims regarding DNN–human correspondences in vision and other domains of cognition. We explore all these issues in this response.
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.
Deep problems with neural network models of human vision
- Jeffrey S. Bowers, Gaurav Malhotra, Marin Dujmović, Milton Llera Montero, Christian Tsvetkov, Valerio Biscione, Guillermo Puebla, Federico Adolfi, John E. Hummel, Rachel F. Heaton, Benjamin D. Evans, Jeffrey Mitchell, Ryan Blything
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- Behavioral and Brain Sciences / Volume 46 / 2023
- Published online by Cambridge University Press:
- 01 December 2022, e385
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Deep neural networks (DNNs) have had extraordinary successes in classifying photographic images of objects and are often described as the best models of biological vision. This conclusion is largely based on three sets of findings: (1) DNNs are more accurate than any other model in classifying images taken from various datasets, (2) DNNs do the best job in predicting the pattern of human errors in classifying objects taken from various behavioral datasets, and (3) DNNs do the best job in predicting brain signals in response to images taken from various brain datasets (e.g., single cell responses or fMRI data). However, these behavioral and brain datasets do not test hypotheses regarding what features are contributing to good predictions and we show that the predictions may be mediated by DNNs that share little overlap with biological vision. More problematically, we show that DNNs account for almost no results from psychological research. This contradicts the common claim that DNNs are good, let alone the best, models of human object recognition. We argue that theorists interested in developing biologically plausible models of human vision need to direct their attention to explaining psychological findings. More generally, theorists need to build models that explain the results of experiments that manipulate independent variables designed to test hypotheses rather than compete on making the best predictions. We conclude by briefly summarizing various promising modeling approaches that focus on psychological data.
Analysis of call detail records to inform the COVID-19 response in Ghana—opportunities and challenges
- Tracey Li, Rachel Bowers, Omar Seidu, Gloria Akoto-Bamfo, David Bessah, Victor Owusu, Laurent Smeets
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- Data & Policy / Volume 3 / 2021
- Published online by Cambridge University Press:
- 23 June 2021, e11
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Telecommunications data are being explored by many countries as a new source of data that can be incorporated into their national statistical systems. In particular, “mobile positioning data” are increasingly being used to study population movements and population distributions. However, the legal, ethical, and technical complexities of working with this type of data often pose many barriers, which can prevent the data from being used at the times when it is most urgently needed. We demonstrate how having a robust public–private partnership framework, a privacy-preserving technical setup, and a communications strategy already in place, prior to an emergency, can enable governments to harness the advantages of telecommunications data at the times when it is most valuable. However, even once these foundations are in place, the challenges of competing priorities, managing expectations, and maintaining communication with data consumers during a pandemic mean that the potential of the data is not automatically translated into direct impact. This highlights the importance of sensitisation exercises, targeted at potential data users, to make clear the potential and limitations of the data, as well as the importance of being able to maintain direct communication with data users. The views expressed in this work belong solely to the authors and should not be interpreted as the views of their institutions.
7 - Collaboration and Correspondence
- from Part II - Relations
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- By Rachel Bower
- Edited by Jarad Zimbler, University of Birmingham
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- Book:
- The Cambridge Companion to J. M. Coetzee
- Published online:
- 26 April 2020
- Print publication:
- 30 April 2020, pp 122-137
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Summary
J. M. Coetzee is often thought a solitary, reclusive figure, but he has long collaborated with other writers and artists. Correspondence and epistolary conventions also play an important role in Coetzee’s fictional work. This chapter argues that we must look beyond the apparent contradiction between Coetzee the private man and Coetzee the collaborator, to understand conflict as central to his pursuit of dialogue. The chapter explores the ways in which writing, reflection, and critique are at the heart of Coetzee’s collaborative work and suggests that these elements are not at odds with his rejection of the demand for immediate, unplanned speech. The chapter provides detailed readings of Coetzee’s works of correspondence, The Good Story and Here and Now, as well as examining his use of epistolary conventions and techniques in his fiction, particularly in Summertime and Age of Iron. The chapter concludes that Coetzee’s commitment to collaboration and correspondence is simultaneously a resistance to producing a single repeatable life-story or superficial exchange, and that just as mediation is necessary to move beyond the stock phrases of epistolary exchange, so errors and disagreements are essential in creating meaningful dialogue.
Acute neuronal and vascular changes following unilateral cerebellar pedunculotomy in the neonatal rat
- RACHEL M. SHERRARD, ADRIAN J. BOWER
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- Journal:
- The Journal of Anatomy / Volume 191 / Issue 2 / August 1997
- Published online by Cambridge University Press:
- 01 August 1997, pp. 177-189
- Print publication:
- August 1997
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During development of the central nervous system (CNS) both deafferentation and axotomy induce increased neuronal death and result in a smaller brain with diminished function at maturity. Unilateral cerebellar pedunculotomy has been used as a model to study the relative importance of these 2 types of lesion on the survival of developing CNS neurons. Within the cerebellum, unilateral pedunculotomy causes deafferentation of the hemicerebellum and axotomy in the efferent pathway from the ipsilateral deep cerebellar nuclei. This results in a smaller hemicerebellum with normal cortical laminae but no extracerebellar outflow. In order to identify the sequence of events which leads to this altered structure and therefore to understand the relative importance of afferent versus target-derived trophic support, unilateral cerebellar pedunculotomy was performed on neonatal rat pups, aged between 1 and 3 days. The cerebella were analysed for histological and vascular changes after survival times of 0, 3, 6, 9, 12, 18, 21, 24 and 48 h. The results show that the effects of axotomy on the deep cerebellar nuclear neurons begin within 3 h of the lesion and apoptotic neuronal degeneration occurs within 48 h. However, the cerebellar cortical neurons continue to undergo normal histological development for at least 48 h after deafferentation. In addition, since ischaemia induces similar effects, a study of the vascular tree was made. The results indicate that the pedunculotomy does not alter the blood supply to the cerebellum, nor induce ischaemia of the cerebellar neurons. From this it may be hypothesised that target-derived trophic support is more crucial for the survival of immature neurons than is the trophic effect of afferent input.