Abstract:Objective: To determine whether cortical b-amyloid (Ab) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI).Methods: Forty participants with aMCI were included in this study. Cortical Ab depositions were measured by 18 F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum. Circadian BP profiles were measured by 24-hour ambulatory monitor… Show more
“…Mean SUVR amyloid burden for the entire brain (represented as “PET SUVR mean”) of each subject is listed in Table 1 . All Spearman’s rho values and p values for correlations are shown in Table 2 , and larger group PET data previously published [ 25 ]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…All subjects underwent clinical interviews and a standard battery of neuropsychological tests to establish clinical diagnosis via multidisciplinary consensus using standard criteria by a licensed psychometrician at UT Southwestern. Detailed inclusion and exclusion criteria were published previously [ 25 ]. Table 1 shows subject demographics, cognitive test results, sample collection, and APOε genotype for the 24 aMCI subjects.…”
Section: Methodsmentioning
confidence: 99%
“…Three regions-of-interest (ROI) relevant to AD pathology were selected a priori: posterior cingulate (PCC), precuneus, and mean cortex. The mean cortical SUVR was calculated by taking an average of posterior and anterior cingulate, precuneus, temporal, dorsolateral prefrontal, orbital frontal, parietal, and occipital SUVRs [ 25 ].…”
BackgroundWe previously found that subjects with amnestic mild cognitive impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid similar to multiple sclerosis, a central nervous system autoimmune disease. We therefore hypothesized that early neuroinflammation would reflect increases in brain amyloid burden during amnestic mild cognitive impairment.MethodsCerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitive impairment (12 men, 12 women; 66 ± 6 years; 0.5 Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal fluid and blood included immune profiling by multi-parameter flow cytometry, genotyping for apolipoprotein (APO)ε, and quantification of cytokine and immunoglobin levels. Amyloid (A)β deposition was determined by 18F-florbetapir positron emission tomography. Spearman rank order correlations were performed to assess simple linear correlation for parameters including amyloid imaging, central and peripheral immune cell populations, and protein cytokine levels.ResultsSoluble Aβ42 in the cerebrospinal fluid declined as Aβ deposition increased overall and in the precuneous and posterior cingulate cortices. Lymphocyte profiling revealed a significant decline in T cell populations in the cerebrospinal fluid, specifically CD4+ T cells, as Aβ deposition in the posterior cingulate cortex increased. In contrast, increased Aβ burden correlated positively with increased memory B cells in the cerebrospinal fluid, which was exacerbated in APOε4 carriers. For peripheral circulating lymphocytes, only B cell populations decreased with Aβ deposition in the precuneous cortex, as peripheral T cell populations did not correlate with changes in brain amyloid burden.ConclusionsElevations in brain Aβ burden associate with a shift from T cells to memory B cells in the cerebrospinal fluid of subjects with amnestic mild cognitive impairment in this exploratory cohort. These data suggest the presence of cellular adaptive immune responses during Aβ accumulation, but further study needs to determine whether lymphocyte populations contribute to, or result from, Aβ dysregulation during memory decline on a larger cohort collected at multiple centers.Trial registrationAETMCI NCT01146717
Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0910-x) contains supplementary material, which is available to authorized users.
“…Mean SUVR amyloid burden for the entire brain (represented as “PET SUVR mean”) of each subject is listed in Table 1 . All Spearman’s rho values and p values for correlations are shown in Table 2 , and larger group PET data previously published [ 25 ]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…All subjects underwent clinical interviews and a standard battery of neuropsychological tests to establish clinical diagnosis via multidisciplinary consensus using standard criteria by a licensed psychometrician at UT Southwestern. Detailed inclusion and exclusion criteria were published previously [ 25 ]. Table 1 shows subject demographics, cognitive test results, sample collection, and APOε genotype for the 24 aMCI subjects.…”
Section: Methodsmentioning
confidence: 99%
“…Three regions-of-interest (ROI) relevant to AD pathology were selected a priori: posterior cingulate (PCC), precuneus, and mean cortex. The mean cortical SUVR was calculated by taking an average of posterior and anterior cingulate, precuneus, temporal, dorsolateral prefrontal, orbital frontal, parietal, and occipital SUVRs [ 25 ].…”
BackgroundWe previously found that subjects with amnestic mild cognitive impairment exhibit a pro-inflammatory immune profile in the cerebrospinal fluid similar to multiple sclerosis, a central nervous system autoimmune disease. We therefore hypothesized that early neuroinflammation would reflect increases in brain amyloid burden during amnestic mild cognitive impairment.MethodsCerebrospinal fluid and blood samples were collected from 24 participants with amnestic mild cognitive impairment (12 men, 12 women; 66 ± 6 years; 0.5 Clinical Dementia Rating) enrolled in the AETMCI study. Analyses of cerebrospinal fluid and blood included immune profiling by multi-parameter flow cytometry, genotyping for apolipoprotein (APO)ε, and quantification of cytokine and immunoglobin levels. Amyloid (A)β deposition was determined by 18F-florbetapir positron emission tomography. Spearman rank order correlations were performed to assess simple linear correlation for parameters including amyloid imaging, central and peripheral immune cell populations, and protein cytokine levels.ResultsSoluble Aβ42 in the cerebrospinal fluid declined as Aβ deposition increased overall and in the precuneous and posterior cingulate cortices. Lymphocyte profiling revealed a significant decline in T cell populations in the cerebrospinal fluid, specifically CD4+ T cells, as Aβ deposition in the posterior cingulate cortex increased. In contrast, increased Aβ burden correlated positively with increased memory B cells in the cerebrospinal fluid, which was exacerbated in APOε4 carriers. For peripheral circulating lymphocytes, only B cell populations decreased with Aβ deposition in the precuneous cortex, as peripheral T cell populations did not correlate with changes in brain amyloid burden.ConclusionsElevations in brain Aβ burden associate with a shift from T cells to memory B cells in the cerebrospinal fluid of subjects with amnestic mild cognitive impairment in this exploratory cohort. These data suggest the presence of cellular adaptive immune responses during Aβ accumulation, but further study needs to determine whether lymphocyte populations contribute to, or result from, Aβ dysregulation during memory decline on a larger cohort collected at multiple centers.Trial registrationAETMCI NCT01146717
Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0910-x) contains supplementary material, which is available to authorized users.
“…A non-dipping pattern of blood pressure at night is associated with increased brain amyloid [35]. Sleep apnea is one of the most common causes of blood pressure non-dipping.…”
Abstract. To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2 ± 5.1/h; age 58.5 ± 4.1 years; 9 male) and 19 controls (AHI 1.8 ± 1.3/h; age 58.5 ± 4.2 years; 9 male) underwent 60-min dynamic 11 C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.
“…29,30 In our findings, the association between nocturnal SBP and cognition was slightly attenuated, but remained statistically significant even after adjustment for the extent of WMH and brain atrophy. More advanced imaging, taking into account microinfarcts, microbleeds, and cerebrovascular reactivity, and possible nonvascular pathological features (eg, b-amyloid) 31,32 may shed additional light on the mechanistic links between higher nocturnal SBP and lower cognition.…”
BackgroundWhether the association of blood pressure (BP) during sleep (nocturnal BP) with cognition differs by race is unknown.Methods and ResultsParticipants in the GENOA (Genetic Epidemiology Network of Arteriopathy) Study underwent ambulatory BP measurements, brain magnetic resonance imaging, and cognitive function testing (the Rey Auditory Verbal Learning Test, the Digit Symbol Substitution Task, and the Trail Making Test Part B) between 2000 and 2007. We examined multivariable linear regression models of the nocturnal BP‐cognition association. Among 755 participants (mean age, 63 years; 64% women; 42% self‐identified black race; 76% taking antihypertensive medication), mean nocturnal systolic BP (SBP)/diastolic BP was 126/69 mm Hg, daytime SBP/diastolic BP level was 139/82 mm Hg, and mean reduction in SBP from day to night (dipping) was 9%. Among the entire sample, a race interaction was observed in Digit Symbol Substitution Task and Trail Making Test Part B (both P<0.15). Race‐stratified analyses showed that a 1‐SD increase in nocturnal SBP levels was associated with poorer Digit Symbol Substitution Task and log‐transformed Trail Making Test Part B scores (unstandardized regression coefficient [95% confidence interval]: −1.98 [−3.28 to −0.69] and 0.06 [0.004–0.12]; both P<0.05) in black but not white individuals. Additional adjustments for white matter hyperintensity volumes or brain atrophy, measured via brain magnetic resonance imaging, did not change the results. Results were similar when nocturnal SBP dipping was assessed as the exposure, yet daytime SBP levels yielded no association with cognition.ConclusionsNocturnal SBP measurements may be useful in assessing the potential risk for lower cognitive function in middle‐aged and older adults, particularly in black individuals.
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