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Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments.

ABSTRACT: BACKGROUND:Although 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. METHODS:We 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. RESULTS:Trajectory 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. CONCLUSIONS:Our 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.

SUBMITTER: Kim YJ

PROVIDER: S-EPMC6343354 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments.

Kim Yeo Jin YJ Cho Seong-Kyoung SK Kim Hee Jin HJ Lee Jin San JS Lee Juyoun J Jang Young Kyoung YK Vogel Jacob W JW Na Duk L DL Kim Changsoo C Seo Sang Won SW

Alzheimer's research & therapy 20190122 1

<h4>Background</h4>Although 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 gro ...[more]

PMID: 30670089

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Project description:BackgroundAnatomical and functional deficits have been studied in patients with amnestic mild cognitive impairment (MCI). However, it is unclear whether and how the anatomical deficits are related to the functional alterations. Present study aims to characterize the association between anatomical and functional deficits in MCI patients.MethodsSeventeen amnestic MCI patients and 18 healthy aging controls were scanned using a T1 Weighted MPRAGE sequence and a gradient-echo echo-planar imaging sequence. Clinical severity of MCI patients was evaluated by using Clinical Dementia Rating, Mini Mental State Examination (MMSE), Clock Drawing Test, Auditory Verbal Learning Test and Activities of Daily Living. VBM with DARTEL was used to characterize the gray matter deficits in MCI. Regional amplitude of low-frequency (0.01-0.08 Hz) fluctuations (ALFF) was used to evaluate regional functional alteration in MCI and fractional ALFF(fALFF) in slow 4 (0.027-0.073 Hz) and slow 5 (0.01-0.027 Hz) were also calculated.ResultsSignificantly decreased gray matter volume (GMV) was observed in amnestic MCI group mainly in bilateral prefrontal, left temporal and posterior cingulate cortex. Significant positive correlation was observed between the GMV in left inferior frontal gyrus and MMSE scores. Interestingly, decreased ALFF/fALFF was revealed in MCI group compared to controls mainly in prefrontal, left parietal regions and right fusiform gyrus, while the increased ALFF/fALFF was found in limbic and midbrain. Furthermore, the changes of fALFF in MCI in the slow-5 band were greater than those in the slow-4. No significant correlation was found between the morphometric and functional results.ConclusionsFindings from the study document that wide spread brain volume reduction accompanied with decreased and increased regional function in MCI, while the anatomical and functional changes were independently. Therefore, the combination of structural and functional MRI methods would provide complementary information and together advance our understanding of the pathophysiology underlying the symptoms of MCI.

Project description:Alzheimer's disease (AD) is a fatal dementing neurodegenerative disease, currently lacking an efficacious disease-modifying therapy. In the last years, there has been some interest in the use of homotaurine as a potential therapeutic compound for AD, but more work is still needed to prove its efficacy as disease modifier in dementia. Since inflammation is believed to play a key role in AD development, we sought to investigate here the in vivo homotaurine effect on inflammatory response in patients at the earliest stages of AD, i.e., suffering from amnestic mild cognitive impairment (aMCI). Thus, the present study aims to evaluate the effects of homotaurine supplementation on cytokine serum levels and memory performances in MCI patients. Neuropsychological, clinical and cytokine assessment was performed at baseline (T0) and after 1 year (T12) of homotaurine supplementation in 20 patients categorized as carriers (n = 9) or no carriers (n = 11) of the ε4 allele of the apolipoprotein E (APOE) gene, the strongest genetic risk factor for AD. The serum levels of the pro-inflammatory mediators Interleukin (IL) 1β, Tumor necrosis factor-alpha (TNFα), IL-6 and IL-18, contextually with the anti-inflammatory molecules IL-18 binding protein (IL-18BP) and Transforming growth factor-beta (TGFβ), were analyzed to explore significant differences in the inflammatory status between T0 and T12 in the two APOE variant carrier groups. No significant differences over time were observed in patients as for most cytokines, except for IL-18. Following homotaurine supplementation, patients carrying the APOEε4 allele showed a significant decrease in IL-18 (both in its total and IL-18BP unbound forms), in turn associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI may have a positive consequence on episodic memory loss due, at least in part, to homotaurine anti-inflammatory effects. This study strongly suggests that future research should focus on exploring the mechanisms by which homotaurine controls brain inflammation during AD progression.

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Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments.

Publications

Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments.

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