Associations between pain catastrophizing and resting-state functional brain connectivity: Ethnic/race group differences in persons with chronic knee pain.

Chronic pain is a significant public health problem, and the prevalence and societal impact continues to worsen annually. Multiple cognitive and emotional factors are known to modulate pain, including pain catastrophizing, which contributes to pain facilitation and is associated with altered resting-state functional connectivity in pain-related cortical and subcortical circuitry. Pain and catastrophizing levels are reported to be higher in non-Hispanic black (NHB) compared with non-Hispanic White (NHW) individuals. The current study, a substudy of a larger ongoing observational cohort investigation, investigated the pathways by which ethnicity/race influences the relationship between pain catastrophizing, clinical pain, and resting-state functional connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), insula, and primary somatosensory cortex (S1). Participants included 136 (66 NHBs and 70 NHWs) community-dwelling adults with knee osteoarthritis. Participants completed the Coping Strategies Questionnaire-Revised Pain Catastrophizing subscale and Western Ontario and McMaster Universities Osteoarthritis Index. Magnetic resonance imaging data were obtained, and resting-state functional connectivity was analyzed. Relative to NHW, the NHB participants were younger, reported lower income, were less likely to be married, and self-reported greater clinical pain and pain catastrophizing (ps < 0.05). Ethnicity/race moderated the mediation effects of catastrophizing on the relationship between clinical pain and resting-state functional connectivity between the ACC, dlPFC, insula, and S1. These results indicate the NHB and NHW groups demonstrated different relationships between pain, catastrophizing, and functional connectivity. These results provide evidence for a potentially important role of ethnicity/race in the interrelationships among pain, catastrophizing, and resting-state functional connectivity.

Resilience, pain, and the brain: Relationships differ by sociodemographics.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

Clock Drawing Performance Slows for Older Adults After Total Knee Replacement Surgery.

BACKGROUND: Clock drawing is a neurocognitive screening tool used in preoperative settings. This study examined hypothesized changes in clock drawing to command and copy test conditions 3 weeks and 3 months after total knee arthroplasty (TKA) with general anesthesia. METHODS: Participants included 67 surgery and 66 nonsurgery individuals >60 years who completed the digital clock drawing test before TKA (or a pseudosurgery date), and 3 weeks and 3 months postsurgery. Generalized linear mixed models assessed digital clock drawing test latency (ie, total time to completion, seconds between digit placement) and graphomotor output (ie, total number of strokes, clock size). Reliable change analyses examined the percent of participants showing change beyond differences found in nonsurgery peers. RESULTS: After adjusting for age, education, and baseline cognition, both digital clock drawing test latency measures were significantly different for surgery and nonsurgery groups, where the surgery group performed slower on both command and copy test conditions. Reliable change analyses 3 weeks after surgery found that total time to completion was slower among 25% of command and 21% of copy constructions in the surgery group. At 3 months, 18% of surgery participants were slower than nonsurgery peers. Neither graphomotor measure significantly changed over time. CONCLUSIONS: Clock drawing construction slowed for nearly one-quarter of patients after TKA surgery, whereas nonsurgery peers showed the expected practice effect, ie, speed increased from baseline to follow-up time points. Future research should investigate the neurobiological basis for these changes after TKA.

Reliability and Utility of Manual and Automated Estimates of Total Intracranial Volume.

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.

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).

A pilot study evaluating presurgery neuroanatomical biomarkers for postoperative cognitive decline after total knee arthroplasty in older adults.

BACKGROUND: Total knee arthroplasty improves quality of life but is associated with postoperative cognitive dysfunction in older adults. This prospective longitudinal pilot study with a parallel control group tested the hypotheses that (1) nondemented adults would exhibit primary memory and executive difficulties after total knee arthroplasty, and (2) reduced preoperative hippocampus/entorhinal volume would predict postoperative memory change, whereas preoperative leukoaraiosis and lacunae volumes would predict postoperative executive dysfunction. METHODS: Surgery (n = 40) and age-education-matched controls with osteoarthritis (n = 15) completed pre- and postoperative (3 weeks, 3 months, and 1 yr) memory and cognitive testing. Hypothesized brain regions of interest were measured in patients completing preoperative magnetic resonance scans (surgery, n = 31; control, n = 12). Analyses used reliable change methods to identify the frequency of cognitive change at each time point. RESULTS: The incidence of postoperative memory difficulties was shown with delay test indices (i.e., story memory test: 3 weeks = 17%, 3 months = 25%, 1 yr = 9%). Postoperative executive difficulty with measures of inhibitory function (i.e., Stroop Color Word: 3 weeks = 21%, 3 months = 22%, 1 yr = 9%). Hierarchical regression analysis assessing the predictive interaction of group (surgery, control) and preoperative neuroanatomical structures on decline showed that greater preoperative volumes of leukoaraiosis/lacunae were significantly contributed to postoperative executive (inhibitory) declines. CONCLUSIONS: This pilot study suggests that executive and memory declines occur in nondemented adults undergoing orthopedic surgery. Severity of preoperative cerebrovascular disease may be relevant for understanding executive decline, in particular.

Environmental and sociocultural factors are associated with pain-related brain structure among diverse individuals with chronic musculoskeletal pain: intersectional considerations.

Chronic musculoskeletal pain including knee osteoarthritis (OA) is a leading cause of disability worldwide. Previous research indicates ethnic-race groups differ in the pain and functional limitations experienced with knee OA. However, when socioenvironmental factors are included in analyses, group differences in pain and function wane. Pain-related brain structures are another area where ethnic-race group differences have been observed. Environmental and sociocultural factors e.g., income, education, experiences of discrimination, and social support influence brain structures. We investigate if environmental and sociocultural factors reduce previously observed ethnic-race group differences in pain-related brain structures. Data were analyzed from 147 self-identified non-Hispanic black (NHB) and non-Hispanic white (NHW), middle and older aged adults with knee pain in the past month. Information collected included health and pain history, environmental and sociocultural resources, and brain imaging. The NHB adults were younger and reported lower income and education compared to their NHW peers. In hierarchical multiple regression models, sociocultural and environmental factors explained 6-37% of the variance in pain-related brain regions. Self-identified ethnicity-race provided an additional 4-13% of explanatory value in the amygdala, hippocampus, insula, bilateral primary somatosensory cortex, and thalamus. In the rostral/caudal anterior cingulate and dorsolateral prefrontal cortex, self-identified ethnicity-race was not a predictor after accounting for environmental, sociocultural, and demographic factors. Findings help to disentangle and identify some of the factors contributing to ethnic-race group disparities in pain-related brain structures. Numerous arrays of environmental and sociocultural factors remain to be investigated. Further, the differing sociodemographic representation of our NHB and NHW participants highlights the role for intersectional considerations in future research.

Contributions of Cardiovascular Burden, Peripheral Inflammation, and Brain Integrity on Digital Clock Drawing Performance in Non-Demented Older Adults.

BACKGROUND: Greater cardiovascular burden and peripheral inflammation are associated with dysexecutive neuropsychological profiles and a higher likelihood of conversion to vascular dementia. The digital clock drawing test (dCDT) is useful in identifying neuropsychological dysfunction related to vascular etiology. However, the specific cognitive implications of the combination of cardiovascular risk, peripheral inflammation, and brain integrity remain unknown. OBJECTIVE: We aimed to examine the role of cardiovascular burden, inflammation, and MRI-defined brain integrity on dCDT latency and graphomotor metrics in older adults. METHODS: 184 non-demented older adults (age 69±6, 16±3 education years, 46% female, 94% white) completed dCDT, vascular assessment, blood draw, and brain MRI. dCDT variables of interest: total completion time (TCT), pre-first hand latency, digit misplacement, hour hand distance from center, and clock face area. Cardiovascular burden was calculated using the Framingham Stroke Risk Profile (FSRP-10). Peripheral inflammation markers included interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha, and high sensitivity C-reactive protein. Brain integrity included bilateral entorhinal cortex volume, lateral ventricular volume, and whole brain leukoaraiosis. RESULTS: FSRP-10, peripheral inflammation, and brain integrity explained an additional 14.6% of the variance in command TCT, where FSRP-10 was the main predictor. FSRP-10, inflammatory markers, and brain integrity explained an additional 17.0% in command digit misplacement variance, with findings largely driven by FSRP-10. CONCLUSION: Subtle graphomotor behavior operationalized using dCDT metrics (i.e., TCT and digit misplacement) is partly explained by cardiovascular burden, peripheral inflammation, and brain integrity and may indicate vulnerability to a disease process.

Perioperative Extracellular Brain Free-Water Changes for Older Adults Electing Total Knee Arthroplasty with General versus Spinal Anesthesia: A Pilot Study.

BACKGROUND: Recent research shows that older adults electing to undergo total knee arthroplasty with general anesthesia have a pre- to postoperative acute increase in molecular free-water within their cerebral white matter. It is unknown if this change is similar for individuals who elect spinal anesthesia methods. OBJECTIVE: To explore white matter microstructural changes in a pilot sample of older adults undergoing total knee arthroplasty and receiving general or spinal anesthesia. METHODS: We assessed acute perioperative changes in brain white matter free-water in a limited number of older adults electing total knee arthroplasty under spinal anesthesia (n = 5) and matched groups of older adults who received general anesthesia (n = 5) or had no surgery (n = 5). Patterns of free-water changes were also compared in the larger group of older adults electing total knee arthroplasty under general anesthesia (n = 61) and older adults with chronic knee pain who received no surgical intervention (n = 65). RESULTS: Our pilot results suggest older adults receiving general anesthesia had pre- to post-surgery free-water increases extensively throughout their white matter whereas those receiving spinal anesthesia appeared to have less consistent free-water increases. CONCLUSIONS: Our pilot results possibly suggest different patterns of perioperative brain white matter free-water changes based on anesthetic approach. We recommend future, larger studies to further examine the effects of anesthetic approach on perioperative brain free-water. The results of our study have potential implications for acute and chronic cognitive changes, perioperative complications, neurodegenerative processes including Alzheimer's disease, and understanding neuroinflammation.

Elucidating individual differences in chronic pain and whole person health with allostatic load biomarkers.

Chronic pain is a stressor that affects whole person functioning. Persistent and prolonged activation of the body's stress systems without adequate recovery can result in measurable physiological and neurobiological dysregulation recognized as allostatic load. We and others have shown chronic pain is associated with measures of allostatic load including clinical biomarker composites, telomere length, and brain structures. Less is known regarding how different measures of allostatic load align. The purpose of the study was to evaluate relationships among two measures of allostatic load: a clinical composite and pain-related brain structures, pain, function, and socioenvironmental measures. Participants were non-Hispanic black and non-Hispanic white community-dwelling adults between 45 and 85 years old with knee pain. Data were from a brain MRI, questionnaires specific to pain, physical and psychosocial function, and a blood draw. Individuals with all measures for the clinical composite were included in the analysis (n = 175). Indicating higher allostatic load, higher levels of the clinical composite were associated with thinner insula cortices with trends for thinner inferior temporal lobes and dorsolateral prefrontal cortices (DLPFC). Higher allostatic load as measured by the clinical composite was associated with greater knee osteoarthritis pathology, pain disability, and lower physical function. Lower allostatic load as indicated by thicker insula cortices was associated with higher income and education, and greater physical functioning. Thicker insula and DLPFC were associated with a lower chronic pain stage. Multiple linear regression models with pain and socioenvironmental measures as the predictors were significant for the clinical composite, insular, and inferior temporal lobes. We replicate our previously reported bilateral temporal lobe group difference pattern and show that individuals with high chronic pain stage and greater socioenvironmental risk have a higher allostatic load as measured by the clinical composite compared to those individuals with high chronic pain stage and greater socioenvironmental buffers. Although brain structure differences are shown in individuals with chronic pain, brain MRIs are not yet clinically applicable. Our findings suggest that a clinical composite measure of allostatic load may help identify individuals with chronic pain who have biological vulnerabilities which increase the risk for poor health outcomes.

Elucidating factors contributing to disparities in pain-related experiences among adults with or at risk for knee osteoarthritis.

Background and purpose: We and others have reported ethnic/race group differences in clinical pain, physical function, and experimental pain sensitivity. However, recent research indicates that with consideration for socioenvironmental factors, ethnicity/race differences become less or non-significant. Understanding of factors contributing to pain inequities are needed. Guided by the NIA and NIMHD Health Disparities Research Frameworks, we evaluate the contributions of environmental and behavioral factors on previously reported ethnic/race group differences in: (1) clinical pain, (2) physical function, and (3) experimental pain in individuals with knee pain. Methods: Baseline data from Understanding of Pain and Limitations in Osteoarthritis Disease (UPLOAD) and UPLOAD-2 studies were analyzed. Participants were adults 45 to 85 years old who self-reported as non-Hispanic white (NHW) or black (NHB) with knee pain. A health assessment and quantitative sensory testing were completed. Sociodemographics, environmental, health, clinical and experimental pain, and physical functioning measures were included in nested regressions. Results: Pooled data from 468 individuals, 57 ± 8 years of age, 63% women, and 53% NHB adults. As NHB adults were younger and reported greater socioenvironmental risk than the NHW adults, the term sociodemographic groups is used. With inclusion of recognized environmental and behavioral variables, sociodemographic groups remained a significant predictor accounting for <5% of the variance in clinical pain and physical function and <10% of variance in experimental pain. Conclusion: The incorporation of environmental and behavioral factors reduced relationships between sociodemographic groups and pain-related outcomes. Pain sites, BMI, and income were significant predictors across multiple models. The current study adds to a body of research on the complex array of factors contributing to disparities in pain-related outcomes.

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes.

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. METHODS: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. RESULTS: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). IMPLICATIONS: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes.

Free Water Fraction Predicts Cognitive Decline for Individuals with Idiopathic Parkinson's disease.

INTRODUCTION: Free water fraction (FWF) is considered a metric of microstructural integrity and may be useful in predicting cognitive decline in idiopathic Parkinson's Disease (PD). We sought to determine if higher FWF within the dorsal portion of the caudate nucleus and basal nucleus of Meynert, two regions associated with cognitive decline in PD, predict change in cognition over a two-year span. Due to the existence of cognitive and neurophysiological subgroups within PD, we statistically categorized participants based on FWF in these regions. METHODS: At baseline, participants completed a research cognitive protocol followed by MRI structural and diffusion metrics. We used k-means cluster analysis with average FWF values from bilateral basal nucleus of Meynert and dorsal caudate to create data-driven FWF clusters for baseline. Two-year reliable change indices were calculated for metrics of language, visuospatial, memory, cognitive flexibility, and reasoning domains. Reliable change scores were compared between the clusters and non-PD peers. RESULTS: Baseline participants included 174 participants (112 PD, 62 non-PD). Cluster analysis yielded three clusters: low FWF in both regions of interest (ROIs), high FWF in both ROIs, and moderate FWF in both ROIs. Reliable change analyses were completed on 93 participants (67 PD, 26 non-PD). After controlling for age and education, the High FWF cluster declined more than non-PD peers in every domain except memory. CONCLUSION: Individuals with high FWF in regions associated with cognitive decline in PD show significant decline across several cognitive domains compared to non-PD peers. Future research should include FWF in additional cortical regions.

Relationships Between Cognitive Screening Composite Scores and Pain Intensity and Pain Disability in Adults With/At Risk for Knee Osteoarthritis.

OBJECTIVES: Chronic pain, cognitive deficits, and pain-related disability are interrelated. The prevalence of chronic pain and undiagnosed cognitive difficulties in middle age and older adults is increasing. Of the cognitive systems, executive function and episodic memory are most relevant to chronic pain. We examined the hypothesis that cognitive screening composite scores for executive function and memory would negatively associate with pain intensity and pain disability in a group of middle-aged and older adults with knee pain with or at risk for osteoarthritis. METHODS: A total of 120 adults (44 men/76 women), an average age of 59 years, participated in the study. Demographic, health history, clinical pain, and cognitive measures were completed. Relationships between pain intensity, pain disability, and the Montreal Cognitive Assessment (MoCA) total and composite scores were examined with relevant covariates in the model. RESULTS: MoCA raw scores ranged from 13 to 30 with a mean score of 23.9. Pain intensity was negatively associated with overall MoCA total and executive function and memory composite scores. Pain disability over the previous 6 months was negatively associated with executive function, while pain disability over the past 48 hours was not associated with executive function. CONCLUSION: The results of the current study demonstrates associations between pain metrics and cognitive domain scores within a common cognitive screening tool.

The functional connectivity and neuropsychology underlying mental planning operations: data from the digital clock drawing test.

We examined the construct of mental planning by quantifying digital clock drawing digit placement accuracy in command and copy conditions, and by investigating its underlying neuropsychological correlates and functional connectivity. We hypothesized greater digit misplacement would associate with attention, abstract reasoning, and visuospatial function, as well as functional connectivity from a major source of acetylcholine throughout the brain: the basal nucleus of Meynert (BNM). Participants (n = 201) included non-demented older adults who completed all metrics within 24 h of one another. A participant subset met research criteria for mild cognitive impairment (MCI; n = 28) and was compared to non-MCI participants on digit misplacement accuracy and expected functional connectivity differences. Digit misplacement and a comparison dissociate variable of total completion time were acquired for command and copy conditions. a priori fMRI seeds were the bilateral BNM. Command digit misplacement is negatively associated with semantics, visuospatial, visuoconstructional, and reasoning (p's < 0.01) and negatively associated with connectivity from the BNM to the anterior cingulate cortex (ACC; p = 0.001). Individuals with MCI had more misplacement and less BNM-ACC connectivity (p = 0.007). Total completion time involved posterior and cerebellar associations only. Findings suggest clock drawing digit placement accuracy may be a unique metric of mental planning and provide insight into neurodegenerative disease.

Chronic Pain Severity and Sociodemographics: An Evaluation of the Neurobiological Interface.

Chronic pain is variably associated with brain structure. Phenotyping based on pain severity may address inconsistencies. Sociodemographic groups also differ in the experience of chronic pain severity. Whether differences by chronic pain severity and/or sociodemographic groups are indicated in pain-related areas of the brain is unknown. Relations between 2 measures of chronic pain severity and brain structure via T1-weighted MRI were investigated and sociodemographic group differences explored. The observational study included 142 community-dwelling (68 non-Hispanic Black [NHB] and 74 non-Hispanic White [NHW]) adults with/at risk for knee osteoarthritis. Relationships between chronic pain severity, sociodemographic groups, and a priori selected brain structures (postcentral gyrus, insula, medial orbitofrontal, anterior cingulate, rostral middle frontal gyrus, hippocampus, amygdala, thalamus) were explored. Chronic pain severity associated with cortical thickness. NHB participants reported lower sociodemographic protective factors and greater clinical pain compared to NHWs who reported higher sociodemographic protective factors and lower clinical pain. Greater chronic pain severity was associated with smaller amygdala volumes in the NHB group and larger amygdala volumes in the NHW group. Brain structure by chronic pain stage differed between and within sociodemographic groups. Overall, chronic pain severity and sociodemographic factors are associated with pain-related brain structures. Our findings highlight the importance of further investigating social and environmental contributions in the experience of chronic pain to unravel the complex array of factors contributing to disparities. PERSPECTIVE: The study presents data demonstrating structural brain relationships with clinical pain severity, characteristic pain intensity and chronic pain stage, differ by sociodemographic groups. Findings yield insights into potential sources of previous inconsistent pain-brain relationships and highlights the need for future investigations to address social and environmental factors in chronic pain disparities research.

Parkinson's Disease Cognitive Phenotypes Show Unique Clock Drawing Features when Measured with Digital Technology.

BACKGROUND: A companion paper (Crowley et al., 2020) reports on the neuroimaging and neuropsychological profiles of statistically determined idiopathic non-dementia Parkinson's disease (PD). OBJECTIVE: The current investigation sought to further examine subtle behavioral clock drawing differences within the same PD cohort by comparing 1) PD to non-PD peers on digitally acquired clock drawing latency and graphomotor metrics, and 2) PD memory, executive, and cognitively well phenotypes on the same variables. METHODS: 230 matched participants (115 PD, 115 non-PD) completed neuropsychological tests and dCDT. Statistically-derived PD cognitive phenotypes characterized PD participants as PD low executive (PDExe; n = 25), PD low memory (PDMem; n = 34), PD cognitively well (PDWell; n = 56). Using a Bayesian framework and based on apriori hypotheses, we compared groups on: total completion time (TCT), pre-first hand latency (PFHL), post-clock face latency (PCFL), total clock face area (TCFA), and total number of pen strokes. RESULTS: Fewer strokes and slower performance to command were associated with higher odds of PD diagnosis, while a larger clock face in the copy condition was associated with lower odds of PD diagnosis. Within PD cognitive phenotypes, slower performance (TCT, PCFL) and smaller clock face to command were associated with higher odds of being PDExe than PDWell, whereas larger clock faces associated with higher odds of being PDMem than PDWell. Longer disease duration, more pen strokes (command) and smaller clocks (command) associated with higher odds of being PDExe than PDWell. CONCLUSION: Digitally-acquired clock drawing profiles differ between PD and non-PD peers, and distinguish PD cognitive phenotypes.

Functional connectivity of key resting state networks and objectively measured physical activity in older adults with joint pain: A pilot study.

BACKGROUND: Greater brain network integrity may associate with physically active lifestyles. Three resting state networks may provide unique insights into known physical activity-mediated brain health benefits: the default mode network (involved with self-monitoring), the salience network (involved in orienting oneself to salient external and internal stimuli), and the central executive network (responsible for higher level cognitive task). The current study explored relationships between system-wide neural network integrity measured by functional magnetic resonance imaging and objectively-measured physical activity. We hypothesize connectivity patterns as measured by fMRI networks will relate to actigraphy markers such that 1) there will be higher connectivity within the central executive network in more physically active individuals, and 2) there will be higher connectivity within the default mode network and salience network in those with higher levels of physical activity. METHODS: Eighteen non-demented older adults with orthopedic pain (age 67.11 ± 5.61, 50% female, education 15.94 ± 2.51 years) completed brain magnetic resonance imaging, and wore an actigraphy device to objectively measure types of physical and sedentary engagement. RESULTS: Results showed a negative relationship between central executive network connectivity and sedentary time (ß = -0.108, p = .039), and a positive relationship with both moderate-to-vigorous physical activity (ß = 0.629, p = .029) and total activity time (ß = 0.645, p = .039). Results also showed positive relationships for the default mode network (ß = 0.588, p = .033) and the salience network (ß = 0.608, p = .037) with mean cadence (i.e. steps per minute). CONCLUSIONS: Our work adds to the existing literature on specific types of activity measurement (i.e. sedentary time, cadence and moderate-to-vigorous physical activity) which will be useful for interventions aimed at improving the integrity of underlying neural networks.

Statistically Defined Parkinson's Disease Executive and Memory Cognitive Phenotypes: Demographic, Behavioral, and Structural Neuroimaging Comparisons.

BACKGROUND: Some individuals with Parkinson's disease (PD) experience working memory and inhibitory difficulties, others learning and memory difficulties, while some only minimal to no cognitive deficits for many years. OBJECTIVE: To statistically derive PD executive and memory phenotypes, and compare PD phenotypes on disease and demographic variables, vascular risk factors, and specific neuroimaging variables with known associations to executive and memory function relative to non-PD peers. METHODS: Non-demented individuals with PD (n = 116) and non-PD peers (n = 62) were recruited to complete neuropsychology measures, blood draw, and structural magnetic resonance imaging. Tests representing the cognitive domains of interest (4 executive function, 3 memory) were included in a k-means cluster analysis comprised of the PD participants. Resulting clusters were compared demographic and disease-related variables, vascular risk markers, gray/white regions of interest, and white matter connectivity between known regions involved in executive and memory functions (dorsolateral prefrontal cortices to caudate nuclei; entorhinal cortices to hippocampi). RESULTS: Clusters showed: 1) PD Executive, n = 25; 2) PD Memory, n = 35; 3) PD Cognitively Well; n = 56. Even after disease variable corrections, PD Executive had less subcortical gray matter, white matter, and fewer bilateral dorsolateral-prefrontal cortex to caudate nucleus connections; PD Memory showed bilaterally reduced entorhinal-hippocampal connections. PD Cognitively Well showed only reduced putamen volume and right entorhinal cortex to hippocampi connections relative to non-PD peers. Groups did not statistically differ on cortical integrity measures or cerebrovascular disease markers. CONCLUSION: PD cognitive phenotypes showed different structural gray and white matter patterns. We discuss data relative to phenotype demographics, cognitive patterns, and structural brain profiles.

Relationships Between Chronic Pain Stage, Cognition, Temporal Lobe Cortex, and Sociodemographic Variables.

BACKGROUND: Non-Hispanic black (NHB) individuals have increased risk of Alzheimer's disease (AD) relative to non-Hispanic whites (NHW). Ethnicity/race can serve as a proxy sociodemographic variable for a complex representation of sociocultural and environmental factors. Chronic pain is a form of stress with high prevalence and sociodemographic disparities. Chronic pain is linked to lower cognition and accelerated biological aging. OBJECTIVE: The purpose of this study is to seek understanding of potential cognitive and temporal lobe structural brain AD vulnerabilities based on chronic pain stage and ethnicity/race. METHODS: Participants included 147 community dwelling NHB and NHW adults without dementia between 45-85 years old who had or were at risk of knee osteoarthritis. All participants received an MRI (3T Philips), the Montreal Cognitive Assessment (MoCA), and assessment of clinical knee pain stage. RESULTS: There were ethnic/race group differences in MoCA scores but no relationships with chronic knee pain stage. Ethnicity/race moderated the relationship between AD-related temporal lobe thickness and chronic pain stage with quadratic patterns suggesting thinner cortex in high chronic pain stage NHB adults. CONCLUSION: There appear to be complex relationships between chronic knee pain stage, temporal lobe cortex, and sociodemographic variables. Specifically, NHB participants without dementia but with high chronic knee pain stage appeared to have thinner temporal cortex in areas associated with AD. Understanding the effects of sociocultural and socioeconomic factors on health outcomes is the first step to challenging the disparities in healthcare that now appear to link disease conditions to neurodegenerative processes.