Dataset Information

Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.

ABSTRACT:

Objective

To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study.

Methods

Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and Factor VIII) were assessed at baseline in 1,633 participants (mean age 53 [5] years, 60% female, 27% African American) enrolled in the Atherosclerosis Risk in Communities Study. Using all 5 inflammatory markers, an inflammation composite score was created for each participant. We assessed episodic memory and regional brain volumes, using 3T MRI, 24 years later.

Results

Each SD increase in midlife inflammation composite score was associated with 1,788 mm³ greater ventricular (p = 0.013), 110 mm³ smaller hippocampal (p = 0.013), 519 mm³ smaller occipital (p = 0.009), and 532 mm³ smaller Alzheimer disease signature region (p = 0.008) volumes, and reduced episodic memory (p = 0.046) 24 years later. Compared to participants with no elevated (4th quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had, on average, 5% smaller hippocampal and Alzheimer disease signature region volumes. The association between midlife inflammation and late-life brain volume was modified by age and race, whereby younger participants and white participants with higher levels of systemic inflammation during midlife were more likely to show reduced brain volumes subsequently.

Conclusions

Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging.

SUBMITTER: Walker KA

PROVIDER: S-EPMC5705246 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Publications

Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.

Walker Keenan A KA Hoogeveen Ron C RC Folsom Aaron R AR Ballantyne Christie M CM Knopman David S DS Windham B Gwen BG Jack Clifford R CR Gottesman Rebecca F RF

Neurology 20171101 22

<h4>Objective</h4>To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study.<h4>Methods</h4>Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and Factor VIII) were assessed at baseline in 1,633 participants (mean ...[more]

PMID: 29093073

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Project description:ImportanceHearing impairment (HI) in midlife (45-65 years of age) may be associated with longitudinal neurodegeneration of temporal lobe structures, a biomarker of early Alzheimer disease.ObjectiveTo evaluate the association of midlife HI with brain volume trajectories in later life (≥65 years of age).Design, setting, and participantsThis prospective cohort study used data from the Baltimore Longitudinal Study of Aging to evaluate hearing from November 5, 1990, to October 3, 1994, and late-life volume change from July 10, 2008, to January 29, 2015, using magnetic resonance imaging (MRI) (mean follow-up time, 19.3 years). Data analysis was performed from September 22, 2017, to August 27, 2018. A total of 194 community-dwelling older adults who had midlife measures of peripheral hearing at a mean age of 54.5 years and late-life volume change of up to 6 years between the first and most recent MRI assessment were studied. Excluded were those with baseline cognitive impairment, stroke, head injuries, Parkinson disease, and bipolar disorder.ExposuresHearing as measured with pure tone audiometry in each ear from November 5, 1990, to October 3, 1994, and late-life temporal lobe volume change measured by MRI.Main outcomes and measuresLinear mixed-effects models with random intercepts were used to examine the association of midlife hearing (pure tone average of 0.5-4 kHz tones in the better ear and each ear separately) with longitudinal late-life MRI-based measures of temporal lobe structures (hippocampus, entorhinal cortex, parahippocampal gyrus, and superior, middle, and inferior temporal gyri) in the left and right hemispheres, in addition to global and lobar regions, adjusting for baseline demographic characteristics (age, sex, subsequent cognitive impairment status, and educational level) and intracranial volume.ResultsA total of 194 patients (mean [SD] age at hearing assessment, 54.5 [10.0] years; 106 [54.6%] female; 169 [87.1%] white) participated in the study. After Bonferroni correction, poorer midlife hearing in the better ear was associated with steeper late-life volumetric declines in the right temporal gray matter (β = -0.113; 95% CI, -0.182 to -0.044), right hippocampus (β = -0.008; 95% CI, -0.012 to -0.004), and left entorhinal cortex (β = -0.009; 95% CI, -0.015 to -0.003). Poorer midlife hearing in the right ear was associated with steeper late-life volumetric declines in the right temporal gray matter (β = -0.136; 95% CI, -0.197 to -0.075), right hippocampus (β = -0.008; 95% CI, -0.012 to -0.004), and left entorhinal cortex (β = -0.009; 95% CI, -0.015 to -0.003), whereas there were no associations between poorer midlife hearing in the left ear with late-life volume loss.Conclusions and relevanceThe findings suggest that midlife HI is a risk factor for temporal lobe volume loss. Poorer midlife hearing, particularly in the right ear, was associated with declines in hippocampus and entorhinal cortex.

Project description:ObjectivesThis study investigated associations of late midlife sleep characteristics with late-life hearing, which adds to the existing cross-sectional evidence and is novel in examining polysomnographic sleep measures and central auditory processing.MethodsA subset of Atherosclerosis Risk in Communities Study participants underwent sleep assessment in the Sleep Heart Health Study in 1996-1998 and hearing assessment in 2016-2017. Peripheral hearing thresholds (0.5-4kHz) assessed by pure-tone audiometry were averaged to calculate speech-frequency pure-tone average in better-hearing ear (higher pure-tone average=worse hearing). Central auditory processing was measured by the Quick Speech-in-Noise Test (lower score=worse performance). Sleep was measured using polysomnography (time spent in stage 1, stage 2, stage 3/4, rapid eye movement sleep; sleep-disordered breathing [apnea-hypopnea index ≥5]) and self-report (habitual sleep duration; excessive daytime sleepiness [Epworth Sleepiness Scale 10]). Linear regression models adjusted for demographic and lifestyle factors with additional adjustment for cardiovascular factors.ResultsAmong 719 Atherosclerosis Risk in Communities-Sleep Heart Health Study participants (61 ± 5years, 54% female, 100% White), worse speech-frequency pure-tone average was found with sleep-disordered breathing (2.51dB, 95% confidence interval: 0.27, 4.75) and excessive daytime sleepiness (3.35 dB, 95% confidence interval: 0.81, 5.90). Every additional hour of sleep when sleeping >8 hours was associated with worse Quick Speech-in-Noise score (1.61 points, 95% confidence interval: 0.03, 3.19). Every 10-minute increase in rapid eye movement sleep was associated with 0.14-point better Quick Speech-in-Noise score (95% confidence interval: 0.02, 0.25).ConclusionsSleep abnormalities might be risk factors for late-life hearing loss. Future longitudinal studies are needed to confirm these novel findings and clarify the mechanisms.

Dataset Information

Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.

Objective

Methods

Results

Conclusions

Publications

Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.

Similar Datasets

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