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11 Contributions of Cardiovascular Burden, Peripheral Inflammation, and Brain Integrity on Digital Clock Drawing Performance in Non-Demented Older Adults
- Catherine Dion, Jared J. Tanner, David J. Libon, Catherine C. Price
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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. 325-326
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Objective:
Higher cardiovascular burden and peripheral inflammation are associated with small vessel vascular disease, a predominantly dysexecutive cognitive profile, and a higher likelihood of conversion to vascular dementia. The digital clock drawing test, a digitized version of a standard neuropsychological tool, is useful in identifying cognitive dysfunction related to vascular etiology. However, little is known about the specific cognitive implications of vascular risk, peripheral inflammation, and varying levels of overall brain integrity. The current study aimed to examine the role of cardiovascular burden, peripheral inflammation, and brain integrity on digitally acquired clock drawing latency and graphomotor metrics in non-demented older adults.
Participants and Methods:The final prospectively recruited IRB-consented participant sample included 184 non-demented older adults (age: 69±6 years, education: 16±3 years, 46% female, 94% white) who completed digital clock drawing, vascular assessment, blood draw, and brain MRI. Digital clock drawing variables of interest included: total completion time (TCT), pre-first hand latency (PFHL), digit misplacement, hour hand distance from center, and clock face area (CFA). Cardiovascular burden was calculated using the revised version of the Framingham Stroke Risk Profile (FSRP-10). Peripheral inflammation was operationalized using interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-a), and high sensitivity C-reactive protein (hsCRP). The brain integrity composite was comprised of bilateral entorhinal cortex volume, bilateral ventricular volume, and whole brain leukoaraiosis.
Results:Over and above age and cognitive reserve, hierarchical regressions showed FSRP-10, inflammatory markers, and brain integrity explained an additional 13.3% of the variance in command TCT (p< 0.001), with FSRP-10 (p=0.001), IL-10 (p= 0.019), and hsCRP (p= 0.019) as the main predictors in the model. FSRP-10, inflammatory markers, and brain integrity explained an additional 11.7% of the variance in command digit misplacement (p= 0.009), with findings largely driven by FSRP-10 (p< 0.001).
Conclusions:Overall, in non-demented older adults, subtle behavioral nuances seen in digital clock drawing metrics (i.e., total completion time and digit misplacement) are partly explained by cardiovascular burden, peripheral inflammation, and brain integrity over and above age and cognitive reserve. These nuanced behaviors on digitally acquired clock drawing may associate with an emergent disease process or overall vulnerability.
Funding sources: Barber Fellowship; K07AG066813; R01 AG055337; R01 NR014810; American Psychological Foundation Dissertation Award; APA Dissertation Research Award
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.
56 Chronic Musculoskeletal Pain, Biobehavioral and Psychosocial Resilience Index, and Brain Age Gap
- Udell Holmes III, Jared Tanner, Brittany Addison, Kenia Rangel, Angela M Mickle, Cynthia S Garvan, Emily J Bartley, Amber K Brooks, Lai Song, Roland Staud, Burel Goodin, Roger B Fillingim, Catherine C Price, Kimberly T Sibille
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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, p. 465
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Objective:
Chronic musculoskeletal pain is associated with neurobiological, physiological, and cellular measures. Importantly, we have previously demonstrated that a biobehavioral and psychosocial resilience index appears to have a protective relationship on the same biomarkers. Less is known regarding the relationships between chronic musculoskeletal pain, protective factors, and brain aging. This study investigates the relationships between clinical pain, a resilience index, and brain age. We hypothesized that higher reported chronic pain would correlate with older appearing brains, and the resilience index will attenuate the strength of the relationship between chronic pain and brain age.
Participants and Methods:Participants were drawn from an ongoing observational multisite study and included adults with chronic pain who also reported knee pain (N = 135; age = 58.3 ± 8.1; 64% female; 49% non-Hispanic Black, 51% non-Hispanic White; education Mdn = some college; income level Mdn = $30,000 - $40,000; MoCA M = 24.27 ± 3.49). Measures included the Graded Chronic Pain Scale (GCPS), characteristic pain intensity (CPI) and disability, total pain body sites; and a cognitive screening (MoCA). The resilience index consisted of validated biobehavioral (e.g., smoking, waist/hip ratio, and active coping) and psychosocial measures (e.g., optimism, positive affect, negative affect, perceived stress, and social support). T1-weighted MRI data were obtained. Surface area metrics were calculated in FreeSurfer using the Human Connectome Project's multi-modal cortical parcellation scheme. We calculated brain age in R using previously validated and trained machine learning models. Chronological age was subtracted from predicted brain age to generate a brain age gap (BAG). With higher scores of BAG indicating predicated age is older than chronological age. Three parallel hierarchical regression models (each containing one of three pain measures) with three blocks were performed to assess the relationships between chronic pain and the resilience index in relation to BAG, adjusting for covariates. For each model, Block 1 entered the covariates, Block 2 entered a pain score, and Block 3 entered the resilience index.
Results:GCPS CPI (R2 change = .033, p = .027) and GCPS disability (R2 change = 0.038, p = 0.017) significantly predicted BAG beyond the effects of the covariates, but total pain sites (p = 0.865) did not. The resilience index was negatively correlated and a significant predictor of BAG in all three models (p < .05). With the resilience index added in Block 3, both GCPS CPI (p = .067) and GCPS disability (p = .066) measures were no longer significant in their respective models. Additionally, higher education/income (p = 0.016) and study site (p = 0.031) were also significant predictors of BAG.
Conclusions:In this sample, higher reported chronic pain correlated with older appearing brains, and higher resilience attenuated this relationship. The biobehavioral and psychosocial resilience index was associated with younger appearing brains. While our data is cross-sectional, findings are encouraging that interventions targeting both chronic pain and biobehavioral and psychosocial factors (e.g., coping strategies, positive and negative affect, smoking, and social support) might buffer brain aging. Future directions include assessing if chronic pain and resilience factors can predict brain aging over time.
40 Associations Between Cardiovascular Risk, White Matter, and Medication Predictors on Longitudinal Cognitive Change in the National Alzheimer’s Coordinating Center (NACC) Cohort
- Lindsay J Rotblatt, Jared J Tanner, Ronald A Cohen, Ann L Horgas, Michael Marsiske
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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. 349-350
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Objective:
Drawing on the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS), this study aimed to investigate the direct and indirect associations between vascular risk factors/cardiovascular disease (CVD), pharmacological treatment (of CVD), and white matter hyperintensity (WMH) burden on overall cognition and decline trajectories in a cognitively diverse sample of older adults.
Participants and Methods:Participants were 1,049 cognitively diverse older adults drawn from a larger NACC data repository of 22,684 participants whose data was frozen as of December 2019. The subsample included only participants who were aged 60-97 (56.7% women) who completed at least one post-baseline neuropsychological evaluation, had medication data, and both T1 and FLAIR neuroimaging scans. Cognitive composites (Memory, Attention, Executive Function, Language) were derived factor analytically using harmonized data. Baseline WMH volumes were quantified using UBO Detector. Baseline health screening and medication data was used to determine overall CVD burden and total medication. Longitudinal latent growth curve models were estimated adjusting for demographics.
Results:More CVD medication was associated with greater CVD burden; however, no direct effects of medication were found on any of the cognitive composites or WMH volume. While no direct effects of CVD burden on cognition (overall or rate of decline) were observed, instead we found that greater CVD burden had small, but significant, negative indirect effects on Memory, Attention, Executive Functioning and Language (all p’s < .01) after controlling for CVD medication use. Whole brain WMH volume served as the mediator of this relationship, as it did for an indirect effect of baseline CVD on 6-year rate of decline in Memory and Executive function.
Conclusions:Findings from this study were generally consistent with previous literature and extend extant knowledge regarding the direct and indirect associations between CVD burden, pharmacological treatment, and neuropathology of presumed vascular origin on cognitive decline trajectories in an older adult sample. Results reveal the subtle importance of CVD risk factors on late life cognition even after accounting for treatment and WHM volume and highlight the need for additional research to determine sensitive windows of opportunity for intervention.
Reliability and Utility of Manual and Automated Estimates of Total Intracranial Volume
- Samuel J. Crowley, Jared J. Tanner, Daniel Ramon, Nadine A. Schwab, Loren P. Hizel, Catherine C. Price
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- Journal of the International Neuropsychological Society / Volume 24 / Issue 2 / February 2018
- Published online by Cambridge University Press:
- 05 October 2017, pp. 206-211
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Objectives: Total intracranial volume (TICV) is an important control variable in brain–behavior research, yet its calculation has challenges. Manual TICV (Manual) is labor intensive, and automatic methods vary in reliability. To identify an accurate automatic approach we assessed the reliability of two FreeSurfer TICV metrics (eTIV and Brainmask) relative to manual TICV. We then assessed how these metrics alter associations between left entorhinal cortex (ERC) volume and story retention. Methods: Forty individuals with Parkinson’s disease (PD) and 40 non-PD peers completed a brain MRI and memory testing. Manual metrics were compared to FreeSurfer’s Brainmask (a skull strip mask with total volume of gray, white, and most cerebrospinal fluid) and eTIV (calculated using the transformation matrix into Talairach space). Volumes were compared with two-way interclass correlations and dice similarity indices. Associations between ERC volume and Wechsler Memory Scale-Third Edition Logical Memory retention were examined with and without correction using each TICV method. Results: Brainmask volumes were larger and eTIV volumes smaller than Manual. Both automated metrics correlated highly with Manual. All TICV metrics explained additional variance in the ERC-Memory relationship, although none were significant. Brainmask explained slightly more variance than other methods. Conclusions: Our findings suggest Brainmask is more reliable than eTIV for TICV correction in brain-behavioral research. (JINS, 2018, 24, 206–211)
Are Parkinson’s Patients More Vulnerable to the Effects of Cardiovascular Risk: A Neuroimaging and Neuropsychological Study
- Jacob D. Jones, Jared J. Tanner, Michael Okun, Catherine C. Price, Dawn Bowers
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- Journal of the International Neuropsychological Society / Volume 23 / Issue 4 / April 2017
- Published online by Cambridge University Press:
- 06 February 2017, pp. 322-331
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Objectives: This study examined whether individuals with Parkinson’s disease (PD) are at increased vulnerability for vascular-related cognitive impairment relative to controls. The underlying assumption behind this hypothesis relates to brain reserve and that both PD and vascular risk factors impair similar fronto-executive cognitive systems. Methods: The sample included 67 PD patients and 61 older controls (total N=128). Participants completed neuropsychological measures of executive functioning, processing speed, verbal delayed recall/memory, language, and auditory attention. Cardiovascular risk was assessed with the Framingham Cardiovascular Risk index. Participants underwent brain imaging (T1 and T2 FLAIR). Trained raters measured total and regional leukoaraiosis (periventricular, deep subcortical, and infracortical). Results: Hierarchical regressions revealed that more severe cardiovascular risk was related to worse executive functioning, processing speed, and delayed verbal recall in both Parkinson patients and controls. More severe cardiovascular risk was related to worse language functioning in the PD group, but not controls. In contrast, leukoaraiosis related to both cardiovascular risk and executive functioning for controls, but not the PD group. Conclusions: Overall, results revealed that PD and cardiovascular risk factors are independent risk factors for cognitive impairment. Generally, the influence of cardiovascular risk factors on cognition is similar in PD patients and controls. (JINS, 2017, 23, 322–331)