Sleep duration and brain MRI measures: Results from the SOL-INCA MRI study.

INTRODUCTION: Sleep duration has been associated with dementia and stroke. Few studies have evaluated sleep pattern-related outcomes of brain disease in diverse Hispanics/Latinos. METHODS: The SOL-INCA (Study of Latinos-Investigation of Neurocognitive Aging) magnetic resonance imaging (MRI) study recruited diverse Hispanics/Latinos (35-85 years) who underwent neuroimaging. The main exposure was self-reported sleep duration. Our main outcomes were total and regional brain volumes. RESULTS: The final analytic sample included n = 2334 participants. Increased sleep was associated with smaller brain volume (ßtotal_brain  = -0.05, p < 0.01) and consistently so in the 50+ subpopulation even after adjusting for mild cognitive impairment status. Sleeping >9 hours was associated with smaller gray (ßcombined_gray  = -0.17, p < 0.05) and occipital matter volumes (ßoccipital_gray  = -0.18, p < 0.05). DISCUSSION: We found that longer sleep duration was associated with lower total brain and gray matter volume among diverse Hispanics/Latinos across sex and background. These results reinforce the importance of sleep on brain aging in this understudied population. HIGHLIGHTS: Longer sleep was linked to smaller total brain and gray matter volumes. Longer sleep duration was linked to larger white matter hyperintensities (WMHs) and smaller hippocampal volume in an obstructive sleep apnea (OSA) risk group. These associations were consistent across sex and Hispanic/Latino heritage groups.

Sleep Duration Is Associated With Subclinical Carotid Plaque Burden.

BACKGROUND: Sleep duration is associated with stroke risk and is 1 of 8 essential components of cardiovascular health according to the American Heart Association. As stroke disproportionately burdens Black and Hispanic populations in the United States, we hypothesized that long and short sleep duration would be associated with greater subclinical carotid atherosclerosis, a precursor of stroke, in the racially and ethnically diverse NOMAS (Northern Manhattan Study). METHODS: NOMAS is a study of community-dwelling adults. Self-reported nightly sleep duration and daytime sleepiness were collected between 2006 and 2011. Carotid plaque presence, total plaque area, and intima-media thickness were measured by ultrasound between 1999 and 2008. Linear and logistic regression models examined the cross-sectional associations of sleep duration groups (primary exposure) or daytime sleepiness (secondary exposure) with measures of carotid atherosclerosis. Models adjusted for age, time between ultrasound and sleep data collection, sex, race and ethnicity, education, health insurance, smoking, alcohol use, physical activity, body mass index, hypertension, diabetes, hypercholesterolemia, and cardiac disease. RESULTS: The sample (n=1553) had a mean age of 64.7±8.5 years and was 61.9% female, 64.8% Hispanic, and 18.2% non-Hispanic Black. Of the sample, 55.6% had carotid plaque, 22.3% reported nightly short sleep (<7 hours), 66.6% intermediate sleep (≥7 and <9 hours), and 11.1% had long sleep (≥9 hours). Compared with intermediate sleep, long sleep was associated with greater odds of carotid plaque presence relative to plaque absence (odds ratio, 1.6 [95% CI, 1.1-2.4]) and larger total plaque area (odds ratio, 1.4 [95% CI, 1.0-1.9]) after full covariate adjustment. Short sleep and daytime sleepiness were not significantly associated with any carotid measures. CONCLUSIONS: The association between long sleep and subclinical carotid atherosclerosis may explain prior associations between long sleep and stroke.

Actigraphic sleep patterns and cognitive decline in the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We determined if actigraphy-derived sleep patterns led to 7-year cognitive decline in middle-aged to older Hispanic/Latino adults. METHODS: We examined 1035 adults, 45 to 64 years of age, from the Hispanic Community Health Study/Study of Latinos. Participants had repeated measures of cognitive function 7 years apart, home sleep apnea studies, and 1 week of actigraphy. Survey linear regression evaluated prospective associations between sleep and cognitive change, adjusting for main covariates. RESULTS: Longer sleep-onset latency was associated with declines in global cognitive function, verbal learning, and verbal memory. Longer sleep-onset latency was also cross-sectionally associated with verbal learning, verbal memory, and word fluency. Sleep fragmentation was not associated with cognitive change. CONCLUSION: In a cohort of mostly middle-aged Hispanic/Latinos, actigraphy-derived sleep-onset latency predicted 7-year cognitive change. These findings may serve as targets for sleep interventions of cognitive decline.

Amyloid-Beta Deposition is Associated with Increased Medial Temporal Lobe Activation during Memory Encoding in the Cognitively Normal Elderly.

BACKGROUND: Much is unknown about changes that occur in the brain in the years preceding the cognitive and functional impairment associated with Alzheimer disease (AD). This period before mild cognitive impairment is present has been referred to as preclinical AD, and is thought to begin with amyloid-beta deposition and then progress to neurodegeneration and functional brain circuit alterations. Prior studies have shown that there is increased medial temporal lobe activation on functional magnetic resonance imaging (fMRI) early in the course of mild cognitive impairment. It is unknown, however, whether this altered fMRI activity precedes cognitive impairment. The purpose of this study is to address this question using Pittsburgh Compound-B (PiB) imaging and fMRI in a sample of cognitively normal older adults. METHODS: Forty-four cognitively normal older adults underwent both PiB imaging and fMRI with a face-name memory task: 21 were classified as PiB(+) and 23 were PiB(-). Additionally, thorough cognitive and neuropsychological test batteries were administered outside the scanner. The main outcome measure in this study is fMRI activation in the medial temporal lobe during a face-name memory-encoding task. RESULTS: PiB(+) subjects showed higher fMRI activation during the memory task in the hippocampus relative to PiB(-) participants. CONCLUSIONS: The increased medial temporal lobe activation in preclinical AD, observed in this study, may serve as an early biomarker of neurodegeneration. Future studies are needed to clarify whether this functional biomarker can stratify AD risk among PiB(+) older adults.

Associations Between Vascular Risk Factors and Perivascular Spaces in Adults with Intact Cognition, Mild Cognitive Impairment, and Dementia.

BACKGROUND: Perivascular spaces (PVS) are fluid-filled compartments surrounding small intracerebral vessels that transport fluid and clear waste. OBJECTIVE: We examined associations between PVS count, vascular and neurodegenerative risk factors, and cognitive status among the predominantly Hispanic participants of the FL-VIP Study of Alzheimer's Disease Risk. METHODS: Using brain MRI (n = 228), we counted PVS in single axial image through the basal ganglia (BG) and centrum semiovale (CSO). PVS per region were scored as 0 (none), 1 (<10), 2 (11-20), 3 (21-40), and 4 (>40). Generalized linear models examined PVS associations with vascular risk factors and a composite vascular comorbidity risk (VASCom) score. RESULTS: Our sample (mean age 72±8 years, 61% women, 60% Hispanic, mean education 15±4 years, 33% APOE4 carriers) was 59% hypertensive, 21% diabetic, 66% hypercholesteremic, and 30% obese. Mean VASCom score was 2.3±1.6. PVS scores ranged from 0-4 in the BG (mean 1.3±0.7) and CSO (mean 1.2±0.9), and 0-7 combined (mean 2.5±1.4). In multivariable regression models, BG PVS was associated with age (ß= 0.03/year, p < 0.0001), Hispanic ethnicity (ß= 0.29, p = 0.01), education (ß= 0.04/year, p = 0.04), and coronary bypass surgery (ß= 0.93, p = 0.02). CSO PVS only associated with age (ß= 0.03/year, p < 0.01). APOE4 and amyloid-ß were not associated with PVS. CONCLUSION: BG PVS may be a marker of subclinical cerebrovascular disease. Further research is needed to validate associations and identify mechanisms linking BG PVS and cerebrovascular disease markers. PVS may be a marker of neurodegeneration despite our negative preliminary findings and more research is warranted. The association between BG PVS and Hispanic ethnicity also requires further investigation.

Inactivation of astroglial NF-kappa B promotes survival of retinal neurons following ischemic injury.

Reactive astrocytes have been implicated in neuronal loss following ischemic stroke. However, the molecular mechanisms associated with this process are yet to be fully elucidated. In this work, we tested the hypothesis that astroglial NF-kappaB, a key regulator of inflammatory responses, is a contributor to neuronal death following ischemic injury. We compared neuronal survival in the ganglion cell layer (GCL) after retinal ischemia-reperfusion in wild-type (WT) and in GFAP-IkappaBalpha-dn transgenic mice, where the NF-kappaB classical pathway is suppressed specifically in astrocytes. The GFAP-IkappaBalpha-dn mice showed significantly increased survival of neurons in the GCL following ischemic injury as compared with WT littermates. Neuroprotection was associated with significantly reduced expression of pro-inflammatory genes, encoding Tnf-alpha, Ccl2 (Mcp1), Cxcl10 (IP10), Icam1, Vcam1, several subunits of NADPH oxidase and NO-synthase in the retinas of GFAP-IkappaBalpha-dn mice. These data suggest that certain NF-kappaB-regulated pro-inflammatory and redox-active pathways are central to glial neurotoxicity induced by ischemic injury. The inhibition of these pathways in astrocytes may represent a feasible neuroprotective strategy for retinal ischemia and stroke.

Applications of magnetic resonance imaging for treatment-resistant late-life depression.

Late-life depression (LLD) is a growing public and global health concern with diverse clinical manifestations and etiology. This literature review summarizes neuroimaging findings associated with depression in older adults and treatment-response variability. LLD has been associated with cerebral atrophy, diminished myelin integrity, and cerebral lesions in frontostriatal-limbic regions. These associations help explain the depression-executive dysfunction syndrome observed in LLD, and support cerebrovascular burden as a pathogenic mechanism. Furthermore, this review suggests that neuroimaging determinants of treatment resistance also reflect cerebrovascular burden. Of the theoretical etiologies of LLD, cerebrovascular burden may mediate treatment resistance. This review proposes that neuroimaging has the potential for clinical translation. Controlled trials may identify neuroimaging biomarkers that may inform treatment by identifying depressed adults likely to remit with pharmacotherapy, identifying individualized therapeutic dose, and facilitating earlier treatment response measures. Neuroimaging also has the potential to similarly inform treatment response variability from treatment with aripiprazole (dopamine modulator) and buprenorphine (opiate modulator).

La depresión en la edad avanzada (DEA) es una preocupación creciente de salud general y pública, con diversas manifestaciones clínicas y etiologías. Este artículo revisa de manera resumida los hallazgos de las neuroimágenes asociados con la depresión en adultos mayores y la variabilidad de la respuesta terapéutica. La DEA se ha asociado con atrofia cerebral, disminución de la integridad de la mielina y lesiones cerebrales en las regiones límbicas-frontoestriatales. Estas asociaciones ayudan a explicar el síndrome de disfunción ejecutiva de la depresión observado en la DEA y apoyan la carga cerebrovascular como un mecanismo patogénico. Este artículo sugiere además que los hallazgos esenciales de las neuroimágenes de la resistencia al tratamiento también reflejan la carga cerebrovascular. Entre las teorías etiológicas de la DEA, la carga cerebrovascular puede mediar la resistencia al tratamiento. Esta revisión propone que las neuroimágenes tienen un potencial en la traslación clínica. Los ensayos controlados pueden identificar biomarcadores de neuroimágenes que orienten el tratamiento al identificar adultos con depresión que probablemente remitirán con farmacoterapia, identificar dosis terapéuticas individualizadas y facilitar las mediciones de respuesta terapéutica precoz. Las neuroimágenes también tienen el potencial de orientar de manera similar la variabilidad de la respuesta terapéutica del tratamiento con aripiprazol (modulador dopaminérgico) y con buprenorfina (modulador opiáceo).

La dépression du sujet âgé est un problème croissant de santé publique et mondiale dont l'étiologie et les manifestations cliniques sont variées. Cette revue de la littérature résume les résultats de neuro-imagerie associés à la dépression chez les personnes âgées ainsi que la variabilité de la réponse au traitement. La dépression du sujet âgé s'associe à une atrophie cérébrale, à une perte d'intégrité de la myéline et à des lésions cérébrales dans les régions fronto-striato-limbiques. Ces associations permettent d'expliquer le syndrome de dysfonction exécutive observé dans la dépression du sujet âgé et sont en faveur d'une charge cérébrovasculaire comme mécanisme pathogène. De plus, d'après cet article, les facteurs de la résistance au traitement en neuro-imagerie reflètent aussi cette charge. Selon les étiologies théoriques de la dépression du sujet âgé, cette charge cérébrovasculaire jouerait un rôle de médiateur dans la résistance au traitement. Cet article propose que la neuro-imagerie en soit la traduction clinique. Des études contrôlées peuvent déterminer des biomarqueurs de neuro-imagerie qui renseigneraient le traitement en identifiant les adultes déprimés susceptibles de guérir avec un traitement médicamenteux, en précisant la dose thérapeutique personnalisée et en facilitant les mesures précoces de réponse au traitement. La neuro-imagerie peut également informer de la même façon sur la variabilité de la réponse au traitement avec l'aripiprazole (modulateur de la dopamine) et avec la buprénorphine (modulateur opiacé).

Phosphatidylserine-containing liposomes promote maximal survival of retinal neurons after ischemic injury.

We investigated the systemic effect of liposomes bearing apoptotic signals on the level of inflammation and neuronal death induced by ischemia-reperfusion (IR). Using a model of retinal ischemia, we showed that treatment with phosphatidylserine (PS) and phosphatidylcholine (PC) liposomes significantly reduced the expression of proinflammatory genes, including that of Il1b, Il6, Ccl2, Ccl5, Cxcl10, and Icam1, 24 h after reperfusion. Phosphatidylserine liposome treatment was the most efficient and correlated with significantly reduced neuronal death in the retina 7 days after reperfusion. The results of our study indicate that therapeutic strategy based on mimicking a systemic increase in apoptotic signaling can significantly reduce central nervous system damage induced by IR and improve neurologic outcome.