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Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment.

ABSTRACT: There is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI).To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI.From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ?4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation.The MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ?4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia.Although the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD.

SUBMITTER: Alegret M

PROVIDER: S-EPMC4111792 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment.

Alegret Montserrat M Cuberas-Borrós Gemma G Espinosa Ana A Valero Sergi S Hernández Isabel I Ruíz Agustín A Becker James T JT Rosende-Roca Maitée M Mauleón Ana A Sotolongo Oscar O Castell-Conesa Joan J Roca Isabel I Tárraga Lluís L Boada Mercè M

Journal of Alzheimer's disease : JAD 20140101 3

<h4>Background</h4>There is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI).<h4>Objectives</h4>To identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI.<h4>Methods</h4>From an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 n ...[more]

PMID: 24685632

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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.

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Project description:A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-positron emission tomography for monitoring early Alzheimer's disease progression.

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Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment.

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Cognitive, genetic, and brain perfusion factors associated with four year incidence of Alzheimer's disease from mild cognitive impairment.

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