The Association of Neighborhood Socioeconomic Status with Executive Function and Processing Speed in Cognitively Normal Mexican American Elders from the Health and Aging Brains Study: Health Disparities Cohort.

INTRODUCTION: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). METHODS: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. RESULTS: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. CONCLUSION: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline.

Basal Cell Carcinoma With Metastasis to the Thoracic Spine: An Uncommon Case Report and Review of the Literature.

Basal cell carcinoma is an exceedingly rare cause of spinal metastatic disease for which the treatment algorithm is poorly defined. We present a positive patient outcome after treatment of T8 metastatic basal with posterior decompression and fusion followed by later anterior reconstruction, in addition to targeted radiation therapy and pharmacologic therapy. In general, a personalized and comprehensive treatment approach should be used, incorporating surgical, oncologic, and pharmacologic methods as able. Moreover, primary preventive medical and mental health care can help prevent delayed presentation and increased access to timely care.

Evaluation of Neighborhood-Level Disadvantage and Cognition in Mexican American and Non-Hispanic White Adults 50 Years and Older in the US.

Importance: Understanding how socioeconomic factors are associated with cognitive aging is important for addressing health disparities in Alzheimer disease. Objective: To examine the association of neighborhood disadvantage with cognition among a multiethnic cohort of older adults. Design, Setting, and Participants: In this cross-sectional study, data were collected between September 1, 2017, and May 31, 2022. Participants were from the Health and Aging Brain Study-Health Disparities, which is a community-based single-center study in the Dallas/Fort Worth area of Texas. A total of 1614 Mexican American and non-Hispanic White adults 50 years and older were included. Exposure: Neighborhood disadvantage for participants' current residence was measured by the validated Area Deprivation Index (ADI); ADI Texas state deciles were converted to quintiles, with quintile 1 representing the least disadvantaged area and quintile 5 the most disadvantaged area. Covariates included age, sex, and educational level. Main Outcomes and Measures: Performance on cognitive tests assessing memory, language, attention, processing speed, and executive functioning; measures included the Spanish-English Verbal Learning Test (SEVLT) Learning and Delayed Recall subscales; Wechsler Memory Scale, third edition (WMS-III) Digit Span Forward, Digit Span Backward, and Logical Memory 1 and 2 subscales; Trail Making Test (TMT) parts A and B; Digit Symbol Substitution Test (DSST); Letter Fluency; and Animal Naming. Raw scores were used for analyses. Associations between neighborhood disadvantage and neuropsychological performance were examined via demographically adjusted linear regression models stratified by ethnic group. Results: Among 1614 older adults (mean [SD] age, 66.3 [8.7] years; 980 women [60.7%]), 853 were Mexican American (mean [SD] age, 63.9 [7.9] years; 566 women [66.4%]), and 761 were non-Hispanic White (mean [SD] age, 69.1 [8.7] years; 414 women [54.4%]). Older Mexican American adults were more likely to reside in the most disadvantaged areas (ADI quintiles 3-5), with 280 individuals (32.8%) living in ADI quintile 5, whereas a large proportion of older non-Hispanic White adults resided in ADI quintile 1 (296 individuals [38.9%]). Mexican American individuals living in more disadvantaged areas had worse performance than those living in ADI quintile 1 on 7 of 11 cognitive tests, including SEVLT Learning (ADI quintile 5: ß = -2.50; 95% CI, -4.46 to -0.54), SEVLT Delayed Recall (eg, ADI quintile 3: ß = -1.11; 95% CI, -1.97 to -0.24), WMS-III Digit Span Forward (eg, ADI quintile 4: ß = -1.14; 95% CI, -1.60 to -0.67), TMT part A (ADI quintile 5: ß = 7.85; 95% CI, 1.28-14.42), TMT part B (eg, ADI quintile 5: ß = 31.5; 95% CI, 12.16-51.35), Letter Fluency (ADI quintile 4: ß = -2.91; 95% CI, -5.39 to -0.43), and DSST (eg, ADI quintile 5: ß = -4.45; 95% CI, -6.77 to -2.14). In contrast, only non-Hispanic White individuals living in ADI quintile 4 had worse performance than those living in ADI quintile 1 on 4 of 11 cognitive tests, including SEVLT Learning (ß = -2.35; 95% CI, -4.40 to -0.30), SEVLT Delayed Recall (ß = -0.95; 95% CI, -1.73 to -0.17), TMT part B (ß = 15.95; 95% CI, 2.47-29.44), and DSST (ß = -3.96; 95% CI, -6.49 to -1.43). Conclusions and Relevance: In this cross-sectional study, aging in a disadvantaged area was associated with worse cognitive functioning, particularly for older Mexican American adults. Future studies examining the implications of exposure to neighborhood disadvantage across the life span will be important for improving cognitive outcomes in diverse populations.

Plasma Biomarkers of Alzheimer's Disease Are Associated with Physical Functioning Outcomes Among Cognitively Normal Adults in the Multiethnic HABS-HD Cohort.

In this study, we examined the link between plasma Alzheimer's disease (AD) biomarkers and physical functioning outcomes within a community-dwelling, multiethnic cohort. Data from 1 328 cognitively unimpaired participants (n = 659 Mexican American and n = 669 non-Hispanic White) from the ongoing Health & Aging Brain Study-Health Disparities (HABS-HD) cohort were examined. Plasma AD biomarkers (amyloid beta [Aß]40, Aß42, total tau [t-tau], and neurofilament light chain [NfL]) were assayed using the ultra-sensitive Simoa platform. Physical functioning measures were the Timed Up and Go (TUG) and the Short Physical Performance Battery (SPPB). Cross-sectional linear regression analyses revealed that plasma Aß 40 (p < .001), Aß 42 (p = .003), and NfL (p < .001) were each significantly associated with TUG time in seconds. Plasma Aß 40 (p < .001), Aß 42 (p < .001), t-tau (p = .002), and NfL (p < .001) were each significantly associated with SPPB Total Score. Additional analyses demonstrate that the link between plasma AD biomarkers and physical functioning outcomes were strongest among Mexican Americans. Plasma AD biomarkers are receiving a great deal of attention in the literature and are now available clinically including use in clinical trials. The examination of AD biomarkers and physical functioning may allow for the development of risk profiles, which could stratify a person's risk for neurodegenerative diseases, such as AD, based on plasma AD biomarkers, physical functioning, ethnicity, or a combination of these measures prior to the onset of cognitive impairment.

Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort.

Background: Due to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aß40, Aß42, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults. Methods: A total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study-Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age. Results: Significant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aß40, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aß40, Aß42, and t tau there was no difference between the groups for Aß42. NHW had significantly higher levels of Aß40, t tau, and NfL than AA. AA had a higher Aß42/Aß40 ratio than either NHW or MA for CU MCI. Conclusions: The use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.

Return of Scapulohumeral Rhythm in Patients After Reverse Shoulder Arthroplasty: A Midterm Stereoradiographic Imaging Analysis.

Background: Reverse shoulder arthroplasty (RSA) is associated with high rates of midterm complications including scapular notching, implant wear, and mechanical impingement. Scapulo-humeral rhythm (SHR), described by Codman in the 1920's, is defined as the ratio of glenohumeral motion to scapulothoracic motion. SHR is used as an indicator of shoulder dysfunction, as alterations in SHR can have profound implications on shoulder biomechanics. The determination of SHR can be hindered by soft-tissue motion artifacts and high radiation burdens associated with traditional surface marker or fluoroscopic analysis. EOS low dose stereoradiographic imaging analysis utilizing 3D model construction from a 2D X-ray series may offer an alternative modality for characterizing SHR following RSA. Methods: Patients (n=10) underwent an EOS imaging analysis to determine SHR at six and twelve months post-RSA. Leveraging 3D models of the implants, 2D/3D image registration methods were used to calculate relative glenohumeral and scapulothoracic positioning at 60, 90 and 120° of shoulder elevation. Subject-specific SHR curves were assessed and midterm changes in post-RSA SHR associated with follow-up time and motion phase were evaluated. Pearson correlations assessed associations between patient-specific factors and post-RSA SHR. Results: Mean post-RSA SHR was 0.81:1 across subjects during the entire midterm postoperative period. As a cohort, post-RSA SHR was more variable for 60-90° of shoulder motion. SHR for 90-120° of motion decreased (0.43:1) at twelve months post-RSA. Post-RSA SHR could be categorized using three relative motion curve patterns, and was not strongly associated with demographic factors such as BMI. 50% of subjects demonstrated a different SHR relative motion curve shape at twelve months post-RSA, and SHR during the 90120° of motion was found to generally decrease at twelve months. Conclusion: Midterm post-RSA SHR was successfully evaluated using EOS technology, revealing lower SHR values (i.e., greater scapulothoracic motion) compared to normal values reported in the literature. SHR continued to change for some subjects during the midterm post-RSA period, with the greatest change during 90-120° of shoulder motion. Study findings suggest that future post RSA rehabilitation efforts to address elevated scapulothoracic motion may benefit from being patient-specific in nature and targeting scapular stabilization during 90-120° of shoulder motion. Level of Evidence: IV.

Vascular risk profile and white matter hyperintensity volume among Mexican Americans and non-Hispanic Whites: The HABLE study.

INTRODUCTION: Among vascular risk factors we hypothesized that an increased prevalence of diabetes in Hispanics would be associated with greater white matter hyperintensity (WMH) volume, which may contribute to cognitive decline. METHODS: A total of 1318 participants (60% female; 49% Hispanic, 51% non-Hispanic White; age 66.2 ± 8.9 years) underwent clinical evaluation and brain magnetic resonance imaging (MRI). WMH volume associations were assessed with age, sex, and ethnicity and then with vascular risk factors in a selective regression model. RESULTS: WMH volume was greater with older age (P < .0001), Hispanic ethnicity (P = .02), and female sex (P = .049). WMH volume was best predicted by age, diastolic blood pressure, hypertension history, hemoglobin A1c (HbA1c), white blood cell count, and hematocrit (P < .01 for all). Elevated HbA1c was associated with greater WMH volume among Hispanics (parameter estimate 0.08 ± 0.02, P < .0001) but not non-Hispanic Whites (parameter estimate 0.02 ± 0.04, P = .5). DISCUSSION: WMH volume was greater in Hispanics, which may be partly explained by increased WMH volume related to elevated HbA1c among Hispanics but not non-Hispanic Whites.

The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study - Health Disparities Cohort.

INTRODUCTION: The APOEε4 allele is the single strongest genetic risk for late-onset Alzheimer's disease (AD). Prior work demonstrates that not only the APOEε4 allele varies by race/ethnicity but also the risk for AD and cognitive impairment conveyed by the APOEε4 allele varies by the racial/ethnic group as well as genetic ancestry. Here, we sought to examine the link between the APOEε4 and neuropsychological functioning among Mexican Americans (MAs). METHODS: Data were examined from 1,633 (852 MAs and 781 non-Hispanic Whites [NHWs]) participants of the Health & Aging Brain Study - Health Disparities (HABS-HD) and were enrolled with all requisite data to be included into the current analyses. RESULTS: The frequency of both ε4 and ε2 alleles was significantly lower among MAs as compared to NHWs. Among MAs, APOEε4 allele presence was associated specifically with poorer immediate and delayed memory (Wechsler Memory Scale - Third Edition [WMS-III] Logical Memory and Spanish-English Verbal Learning Test [SEVLT]). Among NHWs, APOEε4 allele presence was associated with poorer immediate and delayed memory as well as worse executive functioning (Trials B) and verbal fluency (Animal naming). DISCUSSION/CONCLUSION: The APOEε4 allele was associated with poorer cognition across multiple domains among NHWs; however, allele presence was specifically associated with poorer memory performance among MAs. When combined with prior work, the current findings demonstrate that the risk factors associated with cognitive dysfunction differ among MAs as compared to NHWs and require additional investigation.

Proteomic Profiles of Neurodegeneration Among Mexican Americans and Non-Hispanic Whites in the HABS-HD Study.

BACKGROUND: Hispanics are expected to experience the largest increase in Alzheimer's disease (AD) and AD related dementias over the next several decades. However, few studies have examined biomarkers of AD among Mexican Americans, the largest segment of the U.S. Hispanic population. OBJECTIVE: We sought to examine proteomic profiles of an MRI-based marker of neurodegeneration from the AT(N) framework among a multi-ethnic, community-dwelling cohort. METHODS: Community-dwelling Mexican Americans and non-Hispanic white adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T MRI of the brain. A neurodegeneration MRI meta-ROI biomarker for the AT(N) framework was calculated. RESULTS: Data was examined from n = 1,291 participants. Proteomic profiles were highly accurate for detecting neurodegeneration (i.e., N+) among both Mexican Americans (AUC = 1.0) and non-Hispanic whites (AUC = 0.98). The proteomic profile of N + was different between ethnic groups. Further analyses revealed that the proteomic profiles of N + varied by diagnostic status (control, MCI, dementia) and ethnicity (Mexican American versus non-Hispanic whites) though diagnostic accuracy was high for all classifications. CONCLUSION: A proteomic profile of neurodegeneration has tremendous value and point towards novel diagnostic and intervention opportunities. The current findings demonstrate that the underlying biological factors associated with neurodegeneration are different between Mexican Americans versus non-Hispanic whites as well as at different levels of disease progression.

Cartilage and Meniscus Injuries Are More Common in Patients Undergoing Delayed Multiligament Reconstruction.

The purpose of this study was to describe the pattern of meniscus and cartilage pathology in multiligament knee injuries (MLKIs) and determine the relationship between surgical timing and injury mechanism with degree of intra-articular injury. Patients with surgically treated MLKIs over a 15-year period were retrospectively reviewed and grouped based on surgical intervention, time to intervention, and injury mechanism. The presence or absence of meniscus and chondral injury were recorded at the time of surgery. Surgical intervention within 6 weeks of injury was deemed acute, while surgery occurring more than 6 weeks from injury was classified as delayed. Over the 15-year study period, 207 patients with MLKIs were identified. Compared with acutely managed patients, the delayed intervention group had significantly more meniscus (p = 0.03) and cartilage (p < 0.01) pathology. Meniscus injury rates in MLKIs sustained during sporting activity did not differ from nonsporting injuries (p = 0.63). However, the nonsporting group had significantly more chondral injuries (p < 0.01). High-energy injury mechanism was associated with increased cartilage (p = 0.02), but not meniscus (p = 0.61) injury rates. In conclusion, surgical reconstruction of MLKIs delayed for more than 6 weeks was associated with increased meniscus and cartilage pathology.

A blood screening tool for detecting mild cognitive impairment and Alzheimer's disease among community-dwelling Mexican Americans and non-Hispanic Whites: A method for increasing representation of diverse populations in clinical research.

INTRODUCTION: Representation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor. METHODS: Data were examined from the ongoing community-based, multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models. RESULTS: Data were examined from n = 1649 participants (Mexican American n = 866; non-Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups. DISCUSSION: A blood-based screening tool can serve as a method for increasing access to state-of-the-art AD clinical research by bridging between community-based and clinic-based settings.

Plasma Total Tau and Neurobehavioral Symptoms of Cognitive Decline in Cognitively Normal Older Adults.

Depression and related neurobehavioral symptoms are common features of Alzheimer's disease and other dementias. The presence of these potentially modifiable neurobehavioral symptoms in cognitively intact older adults may represent an early indication of pathophysiological processes in the brain. Tau pathology is a key feature of a number of dementias. A number of studies have found an association between tau and neurobehavioral symptoms. The current study investigated the relationship of a blood-based biomarker of tau and symptoms of depression, anxiety, worry, and sleep disturbances in 538 community based, cognitively normal older adults. Logistic regression revealed no significant relationship between plasma total tau and any measures of neurobehavioral symptoms. To assess the impact of level of tau on these relationships, participants were divided into those in the highest quintile of tau and those in the lower four quintiles. Regression analyses showed a significant relationship between level of plasma total tau and measures of depression, apathy, anxiety, worry and sleep. The presence of higher levels of plasma tau and elevated neurobehavioral symptoms may be an early indicator of cognitive decline and prodromal Alzheimer's disease. Longitudinal research is needed to evaluate the impact of these factors on the development of dementia and may suggest areas for early intervention.

Using Fractional Anisotropy Imaging to Detect Mild Cognitive Impairment and Alzheimer's Disease among Mexican Americans and Non-Hispanic Whites: A HABLE Study.

INTRODUCTION: Alzheimer's disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. METHODS: 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health & Aging Brain among Latino Elders (HABLE) community-based study (Mexican American n = 851; non-Hispanic white n = 785). RESULTS: The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. CONCLUSION: Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.

Does Smoking Cessation Prior to Elective Total Joint Arthroplasty Result in Continued Abstinence?

BACKGROUND: Smoking tobacco is a known modifiable risk factor for complications in total joint arthroplasty (TJA) patients. Patients are commonly required to quit smoking prior to TJA. After the early postoperative period, little is known about the long-term implications of this preoperative behavioral change. Our aims were to 1) identify TJA patients that had negative anabasine screen prior to elective TJA and 2) determine the long-term rates of continued smoking abstinence. METHODS: At our institution, TJA patients identified as smokers undergo urine anabasine testing prior to surgery. Between 2009 - 2018 all patients that had elective primary TJA with pre-operative urine anabasine tests were queried. Patients were called post-operatively at mean 52 months (range 15 - 126 months) and surveyed regarding smoking status. Long-term smoking cessation rates were then analyzed along with relapse time frame. The use of quit aid and patient perspective on importance of quitting were also analyzed. RESULTS: 249 smokers that had elective TJA were identified. 124 (50%) participated in the survey, and 93 quit to facilitate surgery. 21 (23%) never resumed smoking, and 32 (34%) were currently abstinent. Just over half of the patients relapsed in the three-month post-operative period (55%). There were no differences in quit aid or patient perspectives between these groups. CONCLUSION: With an increased focus on smoking cessation prior to elective TJA, orthopedics contributes to an important public health initiative. Although national quit rates are in the single digits, 23% of patients were able to quit permanently.Level of Evidence: IV.

The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics.

INTRODUCTION: Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature. METHODS: Community-dwelling Mexican Americans and non-Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository. RESULTS: Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non-Hispanic Whites. DISCUSSION: The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations.

Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study.

Although intermittent hypoxia training (IHT) has proven effective against various clinical disorders, its impact on mild cognitive impairment (MCI) is unknown. This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI). Seven patients with aMCI (age 69 ± 3 years) alternately breathed 10% O2 and room-air, each 5 minutes, for 8 cycles/session, 3 sessions/wk for 8 weeks. The patients' resting arterial pressures fell by 5 to 7 mm Hg (P < .05) and cerebral tissue oxygenation increased (P < .05) following IHT. Intermittent hypoxia training enhanced hypoxemia-induced cerebral vasodilation (P < .05) and improved mini-mental state examination and digit span scores from 25.7 ± 0.4 to 27.7 ± 0.6 (P = .038) and from 24.7 ± 1.2 to 26.1 ± 1.3 (P = .047), respectively. California verbal learning test score tended to increase (P = .102), but trail making test-B and controlled oral word association test scores were unchanged. Adaptation to moderate IHT may enhance cerebral oxygenation and hypoxia-induced cerebrovasodilation while improving short-term memory and attention in elderly patients with aMCI.

Relationship of Neurofilament Light (NfL) and Cognitive Performance in a Sample of Mexican Americans with Normal Cognition, Mild Cognitive Impairment and Dementia.

INTRODUCTION: This study characterized the relationship between plasma NfL and cognition in a community-based sample of older Mexican Americans. METHODS: 544 participants completed a battery of neuropsychological tests and were diagnosed using clinical criteria. NfL was assayed using Simoa. NfL levels across groups and tests were analyzed. RESULTS: Difference in NfL was found between normal and impaired groups and was related to global cognition, processing speed, executive functions and a list of learning tasks with a significant negative effect for all diagnostic groups. NfL had a negative impact on processing speed, attention, executive functions and delayed and recognition memory for both normal and MCI groups. CONCLUSION: The research supports plasma NfL as a marker of cognitive impairment related to neurodegenerative processes in Mexican Americans and may be a marker of early changes in cognition in those with normal cognition and at risk for developing MCI.

Reduced cerebrovascular and cardioventilatory responses to intermittent hypoxia in elderly.

BACKGROUND: The impact of aging on cerebrovascular function and tissue oxygenation during graded hypoxemia is incompletely known. This study compared the age effect on these variables during cyclic hypoxemia-reoxygenation. METHODS: Hypoxia-induced changes in arterial (SaO2) and cerebral tissue (ScO2) O2 saturation, middle cerebral arterial flow velocity (VMCA), estimated cerebral vascular conductance (CVC), heart rate (HR) and ventilation were compared between 12 elderly (71 ± 2 yr, 7 women) and 13 young (24 ± 3 yr, 5 women) adults during the first and fifth 5-min exposures to 10% O2. RESULTS: Although pre-hypoxia SaO2 did not differ between the groups, ScO2 was lower (P < 0.05) in the elderly (68.4 ± 1.2%) than young (73.8 ± 0.9%) adults, commensurate with a lower resting VMCA (P < 0.05). SaO2 fell less sharply (P < 0.05) in the elderly subjects during the first and fifth hypoxia exposures. Moreover, the responses of ScO2, VMCA, CVC, HR and breathing frequency to hypoxia were attenuated in the elderly subjects. Systolic and diastolic arterial pressures fell by 2-6 mmHg during hypoxia in both young and elderly. Thus, hypoxemia developed more gradually in elderly than young adults during normobaric hypoxia, concordant with a reduced metabolic demand in the elderly. CONCLUSIONS: The elderly adults safely tolerated cyclic, moderate hypoxemia which lowered SaO2 by 20-25%, despite dampening of cerebrovascular and cardiac responses to hypoxemia.

Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity.

Mild traumatic brain injury (mTBI) disproportionately affects military service members and is very difficult to diagnose. To-date, there is currently no blood-based, diagnostic biomarker for mTBI cases with persistent post concussive symptoms. To examine the potential of neuronally-derived (NDE) and astrocytic-derived (ADE) exosome cargo proteins as biomarkers of chronic mTBI in younger adults, we examined plasma exosomes from a prospective longitudinal study of combat-related risk and resilience, marine resiliency study II (MRSII). After return from a combat-deployment participants were interviewed to assess TBI exposure while on deployment. Plasma exosomes from military service members with mTBI (mean age, 21.7 years, n = 19, avg. days since injury 151), and age-matched, controls (deployed service members who did not endorse a deployment-related TBI or a pre-deployment history of TBI; mean age, 21.95 years, n = 20) were precipitated and enriched against a neuronal adhesion protein, L1-CAM, and an astrocyte marker, glutamine aspartate transporter (GLAST) using magnetic beads to immunocapture the proteins and subsequently selected by fluorescent activated cell sorting (FACS). Extracted protein cargo from NDE and ADE preparations were quantified for protein levels implicated in TBI neuropathology by standard ELISAs and on the ultra-sensitive single molecule assay (Simoa) platform. Plasma NDE and ADE levels of Aß42 were significantly higher while plasma NDE and ADE levels of the postsynaptic protein, neurogranin (NRGN) were significantly lower in participants endorsing mTBI exposure compared to controls with no TBI history. Plasma NDE and ADE levels of Aß40, total tau, and neurofilament light (NFL), P-T181-tau, P-S396-tau were either undetectable or not significantly different between the two groups. In an effort to understand the pathogenetic potential of NDE and ADE cargo proteins, neuron-like cultures were treated with NDE and ADE preparations from TBI and non-TBI groups. Lastly, we determined that plasma NDE but not ADE cargo proteins from mTBI samples were found to be toxic to neuron-like recipient cells in vitro. These data support the presence of markers of neurodegeneration in NDEs of mTBI and suggest that these NDEs can be used as tools to identify pathogenic mechanisms of TBI.

Levels of α-2 Macroglobulin in cognitively normal Mexican- Americans with Subjective Cognitive Decline: A HABLE Study.

BACKGROUND: The presence of Subjective Cognitive Decline (SCD) in the absence of objective change and the inflammatory biomarker Alpha 2 Macroglobulin (A2M) have both been implicated in preclinical Alzheimer's disease. Mexican Americans are population with high rates of cardiovascular and inflammatory disorders. OBJECTIVES: The current study investigated the levels of A2M in cognitively normal Mexican Americans with and without complaints of cognitive decline. METHOD: 293 (243 females, 50 males) community-based cognitively normal older Mexican Americans from the ongoing Health and Aging Brain among Latino Elders (HABLE) study were grouped based on subjective cognitive decline and blood samples were assayed by electrochemiluminescence to determine levels of A2M. RESULTS: Participants with SCD had significantly higher levels of A2M than those without SCD. Females with SCD had a significantly higher level of A2M. CONCLUSIONS: Results suggest that higher levels of A2M, a marker of neuronal injury, may be involved in subtle changes in cognitive functioning recognizable to persons reporting SCD but too subtle to be objectively measured. Longitudinal research is needed to assess the impact of SDC and A2M in progression to MCI and dementia in Mexican Americans.