Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

Bangen, Katherine J.; Clark, Alexandra L.; Edmonds, Emily C.; Evangelista, Nicole D.; Werhane, Madeleine L.; Thomas, Kelsey R.; Locano, Lyzette E.; Tran, My; Zlatar, Zvinka Z.; Nation, Daniel A.; Bondi, Mark W.; Delano‐Wood, Lisa

doi:10.3389/fnagi.2017.00181

Cited by 49 publications

(51 citation statements)

References 74 publications

(109 reference statements)

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“…The present study found that older adults with lower CD34+ cells actually exhibited greater hippocampal perfusion. This finding is consistent with several prior studies demonstrating hippocampal hyperperfusion in CN older adults at genetic risk for AD [42], those with subtle memory decline [43] and in MCI [44]. Based on these studies, a biphasic model has been hypothesized in which early compensatory changes in neurovascular function lead to an initial hyperperfusion of the hippocampus followed by an eventual decline in perfusion after the onset of AD dementia [45].…”

Section: Discussionsupporting

confidence: 90%

Circulating Progenitor Cells Correlate with Memory, Posterior Cortical Thickness, and Hippocampal Perfusion

Nation

Tan

Dutt

et al. 2017

JAD

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Background Bone marrow-derived progenitor cells survey the vasculature and home to sites of tissue injury where they can promote repair and regeneration. It has been hypothesized that these cells may play a protective role neurodegenerative and vascular cognitive impairment. Objective To evaluate progenitor cell levels in older adults with and without mild cognitive impairment (MCI), and to relate circulating levels to memory, brain volume, white matter lesion volume and cerebral perfusion. Method Thirty-two older adults, free of stroke and cardiovascular disease, were recruited from the community and evaluated for diagnosis of MCI versus cognitively normal (CN). Participants underwent brain MRI and blood samples were taken to quantify progenitor reserve using flow cytometry (CD34+, CD34+CD133+ and CD34+CD133+CD309+ cells). Results Participants with MCI (n=10) exhibited depletion of all CPC markers relative to those who were CN (n=22), after controlling for age, sex and education. Post-hoc age, sex and education matched comparisons (n=10 MCI, n=10 CN) also revealed the same pattern of results. Depletion of CD34+ cells correlated with memory performance, left posterior cortical thickness and bilateral hippocampal perfusion. Participants exhibited low levels of vascular risk and white matter lesion burden that did not correlate with progenitor levels. Conclusions Circulating progenitor cells are associated with cognitive impairment, memory, cortical atrophy, and hippocampal perfusion. We hypothesize that progenitor depletion contributes to, or is triggered by, cognitive decline and cortical atrophy. Further study of progenitor cell depletion in older adults may benefit efforts to prevent or delay dementia.

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Section: Discussionsupporting

confidence: 90%

Circulating Progenitor Cells Correlate with Memory, Posterior Cortical Thickness, and Hippocampal Perfusion

Nation

Tan

Dutt

et al. 2017

JAD

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“…In AD, microvascular abnormalities are probably the most important [ 31 ], which suggest being a therapeutic target of interest. Moreover, our neuroimaging findings together with the clinical results of the same trial [ 17 ] would be in agreement not only with the correlation between blood perfusion of the brain and neuropsychological tests that have been previously described, particularly MMSE scores [ 38 ], but also with possible interactions between Aβ levels, cerebral blood perfusion and cognition [ 39 ]. The ongoing AMBAR (Alzheimer Management by Albumin Replacement) clinical trial (NCT01561053), of which the primary objective is to evaluate cognitive and brain functional changes in AD patients treated with PE with albumin and immunoglobulin [ 40 ], will help to shed light on these relationships.…”

Section: Discussionsupporting

confidence: 90%

Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer’s Disease Patients Treated with Plasma Exchange with 5% Human Albumin

Cuberas-Borrós

Roca

Boada

et al. 2017

JAD

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Background:Recently, modifications of Aβ1-42 levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer’s disease (AD) treated with plasma exchange (PE) with albumin replacement.Objective:To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial.Methods:Patients received between 3 and 18 PE with albumin (Albutein® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline.Results:42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls.Conclusions:Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion.

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“…In addition, to adjust for individual variation in CBF, postcentral gyrus CBF was used as a reference region and included as a covariate in statistical analyses comparing groups on CBF in the ROIs. This region was selected due to its relative sparing in AD ( Thompson et al, 2003 ) and T2DM-related brain atrophy ( Moran et al, 2013 ; Zhang et al, 2014 ) as well as its use as a control region in our prior studies of CBF in older adults at increased risk for AD ( Bangen et al, 2017 ). FreeSurfer-derived intracranial volume was used as a covariate in analyses comparing groups on regional brain volume.…”

Section: Methodsmentioning

confidence: 99%

Reduced Regional Cerebral Blood Flow Relates to Poorer Cognition in Older Adults With Type 2 Diabetes

Bangen

Werhane

Weigand

et al. 2018

Front. Aging Neurosci.

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Type 2 diabetes mellitus (T2DM) increases risk for dementia, including Alzheimer’s disease (AD). Many previous studies of brain changes underlying cognitive impairment in T2DM have applied conventional structural magnetic resonance imaging (MRI) to detect macrostructural changes associated with cerebrovascular disease such as white matter hyperintensities or infarcts. However, such pathology likely reflects end-stage manifestations of chronic decrements in cerebral blood flow (CBF). MRI techniques that measure CBF may (1) elucidate mechanisms that precede irreversible parenchymal damage and (2) serve as a marker of risk for cognitive decline. CBF measured with arterial spin labeling (ASL) MRI may be a useful marker of perfusion deficits in T2DM and related conditions. We examined associations among T2DM, CBF, and cognition in a sample of 49 well-characterized nondemented older adults. Along with a standard T1-weighted scan, a pseudocontinuous ASL sequence optimized for older adults (by increasing post-labeling delays to allow more time for the blood to reach brain tissue) was obtained on a 3T GE scanner to measure regional CBF in FreeSurfer derived regions of interest. Participants also completed a neuropsychological assessment. Results showed no significant differences between individuals with and without T2DM in terms of cortical thickness or regional brain volume. However, adjusting for age, sex, comorbid vascular risk factors, and reference CBF (postcentral gyrus) older adults with T2DM demonstrated reduced CBF in the hippocampus, and inferior temporal, inferior parietal, and frontal cortices. Lower CBF was associated with poorer memory and executive function/processing speed. When adjusting for diabetes, the significant associations between lower regional CBF and poorer executive function/processing speed remained. Results demonstrate that CBF is reduced in older adults with T2DM, and suggest that CBF alterations likely precede volumetric changes. Notably, relative to nondiabetic control participants, those with T2DM showed lower CBF in predilection sites for AD pathology (medial temporal lobe and inferior parietal regions). Findings augment recent research suggesting that perfusion deficits may underlie cognitive decrements frequently observed among older adults with T2DM. Results also suggest that CBF measured with ASL MRI may reflect an early and important marker of risk of cognitive impairment in T2DM and related conditions.

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Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

Cited by 49 publications

References 74 publications

Circulating Progenitor Cells Correlate with Memory, Posterior Cortical Thickness, and Hippocampal Perfusion

Circulating Progenitor Cells Correlate with Memory, Posterior Cortical Thickness, and Hippocampal Perfusion

Longitudinal Neuroimaging Analysis in Mild-Moderate Alzheimer’s Disease Patients Treated with Plasma Exchange with 5% Human Albumin

Reduced Regional Cerebral Blood Flow Relates to Poorer Cognition in Older Adults With Type 2 Diabetes

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