Dataset Information

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

ABSTRACT:

Introduction

Down syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aβ) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data.

Methods

18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants.

Results

The study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices.

Discussion

This study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aβ may be a reliable indicator of MCI-DS in DS.

SUBMITTER: Keator DB

PROVIDER: S-EPMC7233421 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

Keator David B DB Phelan Michael J MJ Taylor Lisa L Doran Eric E Krinsky-McHale Sharon S Price Julie J Ballard Erin E EE Kreisl William C WC Hom Christy C Nguyen Dana D Pulsifer Margaret M Lai Florence F Rosas Diana H DH Brickman Adam M AM Schupf Nicole N Yassa Michael A MA Silverman Wayne W Lott Ira T IT

Alzheimer's & dementia (Amsterdam, Netherlands) 20200417 1

<h4>Introduction</h4>Down syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aβ) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data.<h4>Methods</h4>18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS pa ...[more]

PMID: 32435685

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Project description:Beta-amyloid deposition is one of the earliest pathological markers associated with Alzheimer's disease. Mild cognitive impairment in the setting of beta-amyloid deposition is considered to represent a preclinical manifestation of Alzheimer's disease. In vivo imaging studies are unique in their potential to advance our understanding of the role of beta-amyloid deposition in cognitive deficits in Alzheimer's disease and in mild cognitive impairment. Previous work has shown an association between global cortical measures of beta-amyloid deposition ('amyloid positivity') in mild cognitive impairment with greater cognitive deficits and greater risk of progression to Alzheimer's disease. The focus of the present study was to examine the relationship between the regional distribution of beta-amyloid deposition and specific cognitive deficits in people with mild cognitive impairment and cognitively normal elderly individuals. Forty-seven participants with multi-domain, amnestic mild cognitive impairment (43% female, aged 57-82 years) and 37 healthy, cognitively normal comparison subjects (42% female, aged 55-82 years) underwent clinical and neuropsychological assessments and high-resolution positron emission tomography with the radiotracer 11C-labelled Pittsburgh compound B to measure beta-amyloid deposition. Brain-behaviour partial least-squares analysis was conducted to identify spatial patterns of beta-amyloid deposition that correlated with the performance on neuropsychological assessments. Partial least-squares analysis identified a single significant (P < 0.001) latent variable which accounted for 80% of the covariance between demographic and cognitive measures and beta-amyloid deposition. Performance in immediate verbal recall (R = -0.46 ± 0.07, P < 0.001), delayed verbal recall (R = -0.39 ± 0.09, P < 0.001), immediate visual-spatial recall (R = -0.39 ± 0.08, P < 0.001), delayed visual-spatial recall (R = -0.45 ± 0.08, P < 0.001) and semantic fluency (R = -0.33 ± 0.11, P = 0.002) but not phonemic fluency (R = -0.05 ± 0.12, P < 0.705) negatively covaried with beta-amyloid deposition in the identified regions. Partial least-squares analysis of the same cognitive measures with grey matter volumes showed similar associations in overlapping brain regions. These findings suggest that the regional distribution of beta-amyloid deposition and grey matter volumetric decreases is associated with deficits in executive function and memory in mild cognitive impairment. Longitudinal analysis of these relationships may advance our understanding of the role of beta-amyloid deposition in relation to grey matter volumetric decreases in cognitive decline.

Project description:Patients with Alzheimer's disease have reduced cerebral blood flow measured by arterial spin labelling magnetic resonance imaging, but it is unclear how this is related to amyloid-? pathology. Using 182 subjects from the Alzheimer's Disease Neuroimaging Initiative we tested associations of amyloid-? with regional cerebral blood flow in healthy controls (n = 51), early (n = 66) and late (n = 41) mild cognitive impairment, and Alzheimer's disease with dementia (n = 24). Based on the theory that Alzheimer's disease starts with amyloid-? accumulation and progresses with symptoms and secondary pathologies in different trajectories, we tested if cerebral blood flow differed between amyloid-?-negative controls and -positive subjects in different diagnostic groups, and if amyloid-? had different associations with cerebral blood flow and grey matter volume. Global amyloid-? load was measured by florbetapir positron emission tomography, and regional blood flow and volume were measured in eight a priori defined regions of interest. Cerebral blood flow was reduced in patients with dementia in most brain regions. Higher amyloid-? load was related to lower cerebral blood flow in several regions, independent of diagnostic group. When comparing amyloid-?-positive subjects with -negative controls, we found reductions of cerebral blood flow in several diagnostic groups, including in precuneus, entorhinal cortex and hippocampus (dementia), inferior parietal cortex (late mild cognitive impairment and dementia), and inferior temporal cortex (early and late mild cognitive impairment and dementia). The associations of amyloid-? with cerebral blood flow and volume differed across the disease spectrum, with high amyloid-? being associated with greater cerebral blood flow reduction in controls and greater volume reduction in late mild cognitive impairment and dementia. In addition to disease stage, amyloid-? pathology affects cerebral blood flow across the span from controls to dementia patients. Amyloid-? pathology has different associations with cerebral blood flow and volume, and may cause more loss of blood flow in early stages, whereas volume loss dominates in late disease stages.

Dataset Information

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

Introduction

Methods

Results

Discussion

Publications

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

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