Diagnostic Utility of Novel MRI-Based Biomarkers for Alzheimer's Disease: Diffusion Tensor Imaging and Deformation-Based Morphometry
Authors: Friese, Uwe | Meindl, Thomas | Herpertz, Sabine C. | Reiser, Maximilian F. | Hampel, >Harald | Teipel, Stefan J.
Article Type: Research Article
Abstract: We report evidence that multivariate analyses of deformation-based morphometry and diffusion tensor imaging (DTI) data can be used to discriminate between healthy participants and patients with Alzheimer's disease (AD) with comparable diagnostic accuracy. In contrast to other studies on MRI-based biomarkers which usually only focus on a single modality, we derived deformation maps from high-dimensional normalization of T1-weighted images, as well as mean diffusivity maps and fractional anisotropy maps from DTI of the same group of 21 patients with AD and 20 healthy controls. Using an automated multivariate analysis of the entire brain volume, widespread decreased white matter integrity and …atrophy effects were found in cortical and subcortical regions of AD patients. Mean diffusivity maps and deformation maps were equally effective in discriminating between AD patients and controls (AUC =0.88 vs. AUC=0.85) while fractional anisotropy maps performed slightly inferior. Combining the maps from different modalities in a logistic regression model resulted in a classification accuracy of AUC=0.86 after leave-one-out cross-validation. It remains to be shown if this automated multivariate analysis of DTI-measures can improve early diagnosis of AD in predementia stages. Show more
Keywords: Alzheimer's disease, biomarker, deformation-based morphometry, diagnostic utility, diffusion tensor imaging, MRI
DOI: 10.3233/JAD-2010-1386
Citation: Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 477-490, 2010
Effects of a 6-Month Cognitive Intervention on Brain Metabolism in Patients with Amnestic MCI and Mild Alzheimer's Disease
Authors: Förster, Stefan | Buschert, Verena C. | Teipel, Stefan J. | Friese, Uwe | Buchholz, Hans-Georg | Drzezga, Alexander | Hampel, Harald | Bartenstein, Peter | Buerger, Katharina
Article Type: Research Article
Abstract: The effect of cognitive intervention on brain metabolism in AD is largely unexplored. Therefore, we aimed to investigate cognitive parameters and 18 FDG PET to test for effects of a cognitive intervention in patients with aMCI or mild AD. Patients with aMCI (N = 24) or mild AD (N = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches …to determine longitudinal changes, group-by-time interactions and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left anterior temporal pole and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD. Show more
Keywords: FDG PET, cognitive intervention, cognitive training, cognitive stimulation, Alzheimer's disease, mild cognitive impairment
DOI: 10.3233/JAD-2011-0025
Citation: Journal of Alzheimer's Disease, vol. 26, no. s3, pp. 337-348, 2011
Effects of a 6-Month Cognitive Intervention Program on Brain Metabolism in Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease
Authors: Förster, Stefan | Buschert, Verena C. | Buchholz, Hans-Georg | Teipel, Stefan J. | Friese, Uwe | Zach, Christian | la Fougere, Christian | Rominger, Axel | Drzezga, Alexander | Hampel, Harald | Bartenstein, Peter | Buerger, Katharina
Article Type: Research Article
Abstract: The effect of cognitive intervention on brain metabolism in Alzheimer's disease (AD) is largely unexplored. Therefore, we aimed to investigate clinical cognitive parameters and 18 FDG PET to test for effects of a cognitive intervention in patients with amnestic mild cognitive impairment (aMCI) or mild AD. Patients with aMCI (n = 24) or mild AD (n = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET …images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions, and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left superior temporal- and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD. Show more
Keywords: Alzheimer's disease, cognitive intervention, cognitive stimulation, cognitive training, FDG PET, mild cognitive impairment
DOI: 10.3233/JAD-2011-100996
Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 695-706, 2011
Effects of a Newly Developed Cognitive Intervention in Amnestic Mild Cognitive Impairment and mild Alzheimer's disease: A Pilot Study
Authors: Buschert, Verena C. | Friese, Uwe | Teipel, Stefan J. | Schneider, Philine | Merensky, Wibke | Rujescu, Dan | Möller, Hans-Jürgen | Hampel, Harald | Buerger, Katharina
Article Type: Research Article
Abstract: Recent studies have shown that patients with Alzheimer's disease (AD) and its possible prodromal stage mild cognitive impairment benefit from cognitive interventions. Few studies so far have used an active control condition and determined effects in different stages of disease. We evaluated a newly developed 6-month group-based multicomponent cognitive intervention in a randomized controlled pilot study on subjects with amnestic mild cognitive impairment (aMCI) and mild AD patients. Forty-three subjects with aMCI and mild AD were recruited. Primary outcome measures were change in global cognitive function as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Mini Mental …Status Examination (MMSE). Secondary outcomes were specific cognitive and psychopathological ratings. Thirty-nine patients were randomized to intervention groups (IGs: 12 aMCI, 8 AD) and active control groups (CGs: 12 aMCI, 7 AD). At the end of the study, we found significant improvements in the IGMCI compared to the CGMCI in the ADAS-cog (p = 0.02) and for the secondary endpoint Montgomery Asberg Depression Rating Scale (MADRS) (p < 0.01) Effects on the MMSE score showed a non-significant trend (p = 0.07). In AD patients, we found no significant effect of intervention on the primary outcome measures. In conclusion, these results suggest that participation in a 6-month cognitive intervention can improve cognitive and non-cognitive functions in aMCI subjects. In contrast, AD patients showed no significant benefit from intervention. The findings in this small sample support the use of the intervention in larger scales studies with an extended follow-up period to determine long-term effects. Show more
Keywords: Alzheimer's disease, cognitive intervention, cognitive stimulation, cognitive training, mild cognitive impairment, stage-specific
DOI: 10.3233/JAD-2011-100999
Citation: Journal of Alzheimer's Disease, vol. 25, no. 4, pp. 679-694, 2011