Associations of mid-to-late-life inflammation with late-life mobility and the influences of chronic comorbidities, race, and social determinants of health: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood. METHODS: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and clinically high ≥3 mg/L), with 20-year hsCRP history from midlife (V2-V5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP). Regression models adjusted for demographic, cardiovascular, and SDoH measures; effect modification by the presence of other common chronic conditions (obesity, diabetes, hypertension) and race were examined, with and without accounting for SDoH. RESULTS: High midlife hsCRP was associated with slower late-life gait speed, even among those without chronic conditions in midlife: -4.6 cm/s (95% CI: -6.4, -2.8). Importantly, sustained high hsCRP was associated with a 20-year slowing of -10.0 cm/s (-14.9, -5.1) among those who never experienced obesity, diabetes, or hypertension over the 20-year period. Associations were similar between Black participants, -3.8 cm/s (-6.9, -0.7) and White participants -3.3 (-4.5, -2.2) per interquartile range of midlife hsCRP; effect modifications by chronic conditions and race were unsupported throughout. Results were robust to accounting for SDoH or otherwise; however, worse SDoH was associated with higher inflammation and slower gait speed in both Black and White participants. CONCLUSIONS: Inflammation in midlife may contribute to clinically meaningful late-life slowing of gait speed, even among otherwise healthy-appearing adults and regardless of race and socioeconomic disadvantage. Regular monitoring and interventions for inflammation may be warranted from midlife.

Paragangliomas Arising From the Laryngeal Paraganglia: Thyroid and Laryngeal Paragangliomas With Radiology-Pathology Correlation.

Paragangliomas are neuroendocrine tumors that arise from the embryonic neural crest cells of the extra-adrenal chromaffin and non-chromaffin cellular system. Paragangliomas arising from the laryngeal paraganglia, which occur in the thyroid and larynx, are a rare subset of paragangliomas compared to the more common locations of the carotid body, vagale, jugular, and tympanic paragangliomas. The preoperative diagnosis of both thyroid and laryngeal paragangliomas may pose a challenge due to cytological, pathological, and imaging non-specificity that overlaps with many other neoplasms. These lesions may be associated with significant intraoperative bleeding and complicated excision with adherence to nearby structures, including the recurrent laryngeal nerve. This article discusses the imaging appearance, pathological features, clinical and operative considerations and manifestations, and management of head and neck paragangliomas, as seen in two patients at our institution.

Endurance and gait speed relationships with mild cognitive impairment and dementia.

INTRODUCTION: Slower mobility is associated with mild cognitive impairment (MCI) and dementia. We examined the interaction of endurance with gait speed on prevalent MCI and dementia. METHODS: Cross-sectional multinomial regression in the ARIC cohort (n = 2844 participants; 71 to 94 years; 44% men; 18% Black persons) with cognitive status (normal/MCI/dementia), 4 m gait speed, and endurance (2 minute walk [2MW]). RESULTS: Faster gait speed (up to but not above 1 m/s) and better 2MW were separately associated with lower dementia risk. Good performance in both (2MW = 200 m, gait speed = 1.2 m/s) was associated with 99% lower dementia (Relative Prevalence Ratio [RPR] = 0.01 [95% CI: 0.0 to 0.06]) and 73% lower MCI, RPR = 0.27 (0.15 to 0.48) compared to poor performance in both (2MW = 100 m, gait speed = 0.8 m/s). Models incorporating a gait speed-by-2MW interaction term outperformed gait speed-only models (P < .001). DISCUSSION: Gait speed relationships with dementia diminish at faster gait speeds. Combining endurance with gait speed may yield more sensitive markers of MCI and dementia than gait speed alone.

Relationships of Clinical and Computed Tomography-Imaged Adiposity with Cognition in Middle-Aged and Older African Americans.

Background: Adiposity depots may differentially affect cognition. African Americans (AA) have higher rates of obesity and dementia but lower visceral adipose tissue (VAT) than whites, yet are underrepresented in studies of adiposity and cognition. Our study compared relations of cognitive function to clinical adiposity measures and computed tomography (CT)-imaged abdominal adiposity in AA. Methods: CT-imaged subcutaneous adipose tissue (SAT) and VAT measurements were obtained in the AA cohort of the Genetic Epidemiology Network of Arteriopathy Study (N = 652, mean age 68 ± 8.4 years, 74% females, 59% obese, 82% hypertensive). Clinical adiposity measures included waist circumference (WC) and body mass index (BMI). Global cognition was operationalized as a global cognitive z-score generated from the average of four cognitive domain z-scores. Generalized estimating equations were used to examine cross-sectional associations between individual standardized adiposity measures and cognition, accounting for age, sex, education, smoking status, and familial clustering. A collective model was constructed including multiple supported adiposity measures and age-by-adiposity interactions. Results: In the collective model, higher WC was associated with worse global cognition, ß = -0.12 (95%CI: -0.21, -0.03); higher SAT was associated with better cognition, ß = 0.09 (0.01, 0.18); higher BMI was associated with worse cognition at younger ages with attenuation at older ages (BMI-by-age-interaction p = .004). VAT was not significantly associated with global cognition, ß = -0.03 (-0.07, 0.02). Conclusions: WC may be the simplest and most efficient measure of adiposity to assess with respect to cognition in clinical settings, although studies to determine mechanistic effects of subcutaneous and other adiposity depots on cognition are warranted.

Associations of Brain Structure With Adiposity and Changes in Adiposity in a Middle-Aged and Older Biracial Population.

BACKGROUND: Studies of adiposity and brain pathology in African Americans (AA) are sparse despite higher rates of obesity, dementia, and dementia-associated brain pathology in AA. This study examined relations of adiposity to white matter hyperintensities (WMH) and total brain volume (TBV) in AA and non-Hispanic whites (NHW). METHODS: Waist circumference (WC) and body mass index (BMI) were measured in the Genetic Epidemiology Network of Arteriopathy study at Visits 1 (mean age 57 [±11]) and 2 (mean age 61 [±10], mean 5.2 years later). Brain MRIs were obtained shortly after Visit 2 in 1,702 participants (64% women, 48% AA). Multilevel linear regression using generalized estimating equation estimated associations of adiposity (cross-sectional) or adiposity changes with WMH (accounting for intracranial size) or TBV adjusting for demographics, cardiovascular risk factors, and incorporating adiposity-by-race interactions. Adiposity-by-age interactions were examined. RESULTS: Concurrent TBV was inversely associated with BMI (ß = -2.76 [95% confidence interval (CI): -4.99, -0.53]) and WC (ß = -2.19 [CI: -4.04, -0.34]). Concurrent WMH were negatively associated with BMI (ß = -0.04 [CI: -0.06, -0.01]) and, among NHW, with WC (ß = -0.04 [CI: -0.06, -0.02]) but not with changes in BMI or WC. BMI increases were associated with lower TBV (ß = -16.20, [CI: -30.34, -2.06]) in AA but not in NHW (ß = -2.76 [CI: -14.02, 8.51]), although race-by-adiposity interactions were not supported. WC increases were not associated with MRI outcomes. CONCLUSION: Greater measures of obesity and increases in measures of obesity, which are common in mid-life, could be detrimental to brain health, particularly in AA.