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Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study.

ABSTRACT: We aimed to compare the longitudinal outcome of amnestic mild cognitive impairment (aMCI) patients with significant Pittsburgh Compound B uptake [PiB(+) aMCI] and those without [PiB(-) aMCI]. Cerebral ?-amyloid was measured in 47 patients with aMCI using PiB-positron emission tomography (PET) (31 PiB(+) aMCI and 16 PiB(-) aMCI). Clinical (N?=?47) and neuropsychological follow-up (N?=?37), and follow-up with brain magnetic resonance imaging (N?=?38) and PiB-PET (N?=?30) were performed for three years. PiB(+) aMCI had a higher risk of progression to dementia (hazard ratio?=?3.74, 95% CI?=?1.21-11.58) and faster rate of cortical thinning in the bilateral precuneus and right medial and lateral temporal cortices compared to PiB(-) aMCI. Among six PiB(-) aMCI patients who had regional PiB uptake ratio >1.5 in the posterior cingulate cortex (PCC), three (50.0%) progressed to dementia, and two of them had global PiB uptake ratio >1.5 at the follow-up PiB-PET. Our findings suggest that amyloid imaging is important for predicting the prognosis of aMCI patients, and that it is necessary to pay more attention to PiB(-) aMCI with increased regional PiB uptake in the PCC.

SUBMITTER: Ye BS

PROVIDER: S-EPMC5883059 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study.

Ye Byoung Seok BS Kim Hee Jin HJ Kim Yeo Jin YJ Jung Na-Yeon NY Lee Jin San JS Lee Juyoun J Jang Young Kyoung YK Yang Jin-Ju JJ Lee Jong-Min JM Vogel Jacob W JW Na Duk L DL Seo Sang Won SW

Scientific reports 20180403 1

We aimed to compare the longitudinal outcome of amnestic mild cognitive impairment (aMCI) patients with significant Pittsburgh Compound B uptake [PiB(+) aMCI] and those without [PiB(-) aMCI]. Cerebral β-amyloid was measured in 47 patients with aMCI using PiB-positron emission tomography (PET) (31 PiB(+) aMCI and 16 PiB(-) aMCI). Clinical (N = 47) and neuropsychological follow-up (N = 37), and follow-up with brain magnetic resonance imaging (N = 38) and PiB-PET (N = 30) were performed for three y ...[more]

PMID: 29615677

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Project description:BackgroundAlthough amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer's disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cognitive trajectory, measured by clinical dementia rating sum of boxes (CDR-SOB). Then, we compared the clinical and neuroimaging features among groups classified by cognitive trajectory.MethodsWe retrospectively recruited 278 patients with aMCI who underwent three or more timepoints of neuropsychological testing. They also had magnetic resonance imaging (MRI) including structured three-dimensional volume images. Cortical thickness was measured using surface-based methods. We performed trajectory analyses to classify our aMCI patients according to their progression and investigate their cognitive trajectory using CDR-SOB.ResultsTrajectory analyses showed that patients with aMCI were divided into three groups: stable (61.8%), slow decliner (31.7%), and fast decliner (6.5%). Changes throughout a mean follow-up duration of 3.7 years in the CDR-SOB for the subgroups of stable/slow/fast decliners were 1.3-, 6.4-, and 12-point increases, respectively. Decliners were older and carried apolipoprotein E4 (APOE4) genotypes more frequently than stable patients. Compared with the stable group, decliners showed a higher frequency of aMCI patients with both visual and verbal memory dysfunction, late stage aMCI, and multiple domain dysfunction. In addition, compared with the stable group, the slow decliners showed cortical thinning predominantly in bilateral parietotemporal areas, while the fast decliners showed cortical thinning predominantly in bilateral frontotemporal areas. Both decliner groups showed worse cognitive function in attention, language, visuospatial, memory, and frontal/executive domains than the stable group.ConclusionsOur data-driven trajectory analysis provides new insights into heterogeneous cognitive trajectories of aMCI and further suggests that baseline clinical and neuroimaging profiles might predict aMCI patients with poor prognosis.

Project description:BackgroundAbout 40-50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans.MethodsThis study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together.ResultsDuring the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006).ConclusionOur findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI.

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.

Dataset Information

Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study.

Publications

Longitudinal outcomes of amyloid positive versus negative amnestic mild cognitive impairments: a three-year longitudinal study.

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