Relationships between hippocampal microstructure, metabolism, and function in early Alzheimer's disease.

Abnormal microstructural integrity and glucose metabolism of the hippocampus are common in subjects with Alzheimer's disease (AD) that typically manifest as episodic memory impairment. The above-tissue alterations can be captured in vivo using diffusion tensor imaging (DTI) and positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET). Here, we explored relationships between the above neuroimaging and cognitive markers of early AD-specific hippocampal damage. Twenty patients with early AD (MMSE 25.7 ± 1.7) were studied using DTI and FDG-PET. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). In the between-modality correlation analysis, FDG uptake was strongly associated with diffusivity in the left anterior hippocampus only (r = -0.81, p < 0.05 Bonferroni's corrected for multiple tests). Performance on DVR significantly correlated with left anterior (r = -0.80, p < 0.05) and left mean (r = -0.72, p < 0.05) hippocampal diffusivity, while the correlation with left anterior FDG uptake did not reach statistical significance (r = 0.52, n.s.). DTI-derived diffusivity of the anterior hippocampus might be a sensitive early marker of hippocampal dysfunction as reflected at the synaptic and cognitive levels. This neurobiological distinction of the anterior hippocampus might be related to the disruption of the perforant pathway that is known to occur early in the course of AD.

Occurence and clinical predictors of spasticity after ischemic stroke.

BACKGROUND AND PURPOSE: There is currently no consensus on (1) the percentage of patients who develop spasticity after ischemic stroke, (2) the relation between spasticity and initial clinical findings after acute stroke, and (3) the impact of spasticity on activities of daily living and health-related quality of life. METHODS: In a prospective cohort study, 301 consecutive patients with clinical signs of central paresis due to a first-ever ischemic stroke were examined in the acute stage and 6 months later. At both times, the degree and pattern of paresis and muscle tone, the Barthel Index, and the EQ-5D score, a standardized instrument of health-related quality of life, were evaluated. Spasticity was assessed on the Modified Ashworth Scale and defined as Modified Ashworth Scale >1 in any of the examined joints. RESULTS: Two hundred eleven patients (70.1%) were reassessed after 6 months. Of these, 42.6% (n=90) had developed spasticity. A more severe degree of spasticity (Modified Ashworth Scale >or=3) was observed in 15.6% of all patients. The prevalence of spasticity did not differ between upper and lower limbs, but in the upper limb muscles, higher degrees of spasticity (Modified Ashworth Scale >or=3) were more frequently (18.9%) observed than in the lower limbs (5.5%). Regression analysis used to test the differences between upper and lower limbs showed that patients with more severe paresis in the proximal and distal limb muscles had a higher risk for developing spasticity (P

Increased hippocampal head diffusivity predicts impaired episodic memory performance in early Alzheimer's disease.

Recent neuroanatomical and functional neuroimaging studies indicate that the anterior part of the hippocampus, rather than the whole structure, may be specifically involved in episodic memory. In the present work, we examined whether anterior structural measurements are superior to other regional or global measurements in mapping functionally relevant degenerative alterations of the hippocampus in Alzheimer's disease (AD). Twenty patients with early AD (MMSE 25.7+/-1.7) and 18 healthy controls were studied using magnetic resonance and diffusion-tensor imaging. Using a regions-of-interest analysis, we obtained volumetric and diffusivity measures of the hippocampal head and body-tail-section as well as of the whole hippocampus. Detailed cognitive evaluation was based on the CERAD battery. All volumetric measures as well as diffusivity of the hippocampus head were significantly (p<0.01) altered in patients as compared to controls. In patients, increased left head diffusivity significantly (p<0.01) correlated with performance on free delayed verbal recall test (DVR) (r=-0.74, p=0.0002) and with the CERAD global score. Reduced volume of the left body-tail was also associated with performance on DVR (r=0.62, p=0.004). Stepwise regression analyses revealed that increased left head diffusivity was the only predictor for performance on DVR (R(2)=52%, p<0.0005). These findings suggest that anterior hippocampus diffusivity is more closely related to verbal episodic memory impairment than other regional or global structural measures. Our data support the hypothesis of functional differentiation in general and the specific role of the anterior hippocampus in episodic memory in particular. Diffusivity measurements might be highly sensitive to functionally relevant degenerative alterations of the hippocampus.

Functional relevant loss of long association fibre tracts integrity in early Alzheimer's disease.

The aim of our study was to quantify the structural integrity of the long association fibre tracts in early Alzheimer's disease (AD) and to correlate the findings with the cognitive performance of the patients. We conducted region-of-interest-based analyses of color-coded diffusion-tensor imaging in 12 patients with early AD (age 69.8+/-8.0 years; MMSE 25.3+/-1.8) and 16 age- and education-matched healthy controls. Early AD patients showed significantly decreased fractional anisotropy (FA) of the cingulate bundles and the inferior fronto-occipital fascicles bilaterally, whereas FA values of the superior longitudinal fascicles (second division) did not differ significantly between patients and controls. Neuropsychological performance of patients in the verbal episodic memory test domain correlated significantly with disturbances of left cingulate fibre tract integrity. Reduced left cingulate bundle integrity was most strongly correlated with impaired performance in a verbal recognition task (Spearman's rho=0.81, P=0.001). Moreover, Boston naming test performance also correlated with the left cingulate bundle integrity (Spearman's rho=0.71, P=0.009). These findings suggest substantial disturbances of the structural connectivity within long association fibre tracts, especially the cingulate bundles and the inferior fronto-occipital fascicles, in early AD and highlight the important role of the cingulate bundles in verbal recognition.

Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI.

Hippocampus atrophy is a frequent finding in mild cognitive impairment (MCI), whereas diffusion-tensor-imaging (DTI) has demonstrated its value to detect subtle brain tissue changes in several neuropsychiatric diseases including MCI. To compare the diagnostic accuracy of both methods, high resolution MRI scans for hippocampus volumetry, and co-registered DTI-scans for ROI-based mean diffusivity (MD) and fractional anisotropy (FA) were carried out in 18 patients with amnestic MCI (7 females, age 67.3+/-8.7 years, MMSE 25.2+/-2.2) and 18 controls (age 66.9+/-9.0 years, MMSE 28.7+/-1.0). Diagnostic properties of normalized hippocampus volume (HV) and DTI measures with regard to MCI status were estimated by receiver operating characteristics (ROC) analyses and logistic regression. Parameters of the left hippocampus showed superior predictive power when compared to the right. At a specificity set to 80%, left HV had low sensitivity (50%); left hippocampal MD values revealed superior sensitivity (89%), similar to left hippocampal FA (78%). The results demonstrate higher sensitivity of DTI-derived left hippocampal parameters than volume measures in detecting subtle hippocampal abnormalities related to MCI.

Asymmetry in dopamine D(2/3) receptors of caudate nucleus is lost with age.

Molecular and functional imaging techniques reveal evidence for lateralization of human cerebral function. Based on animal data, we hypothesized that asymmetry in dopamine neurotransmission declines during normal aging. In order to test this hypothesis, we measured dopamine D2/3 receptor availability with [18F]desmethoxyfallypride-PET (DMFP) in putamen and caudate nucleus (NC) of 21 healthy, right-handed males (24-60 years; 35+/-10). For volumetric analysis, high-resolution T1-weighted MR-images were obtained in 18 of the PET-subjects in order to assess possible age-related decreases in NC and putamen volume. The calculated DMFP binding potentials (BP) showed a right-ward asymmetry in NC of young subjects that decreased with age (r = 0.577, p = 0.006; Pearson correlation; two-tailed). An age-independent analysis showed a right-ward asymmetry in NC of the whole subject group (left: 1.49+/-0.35; right: 1.65+/-0.43 [mean+/-S.D.]; p = 0.020). No such side lateralization or age-effects could be found in the putamen. Volumes tended to be asymmetric in the putamen (right: 4.85+/-0.56 cm3; left: 4.64+/-0.86 cm3 [mean+/-S.D.]; p = 0.063), but not in NC. The decline of putamen volume during aging was significant in the right putamen (r = -0.613; p = 0.007; Pearson correlation; two-tailed). There were no other significant correlations between striatal volumes and age or BP. Because ventral striatal dopamine neurotransmission is involved in cognitive processes, this loss of physiological asymmetry in NC dopamine transmission during aging might be involved in age-related declines of cognitive performance.

Functional implications of hippocampal volume and diffusivity in mild cognitive impairment.

Hippocampal atrophy has been related to mild cognitive impairment (MCI) and early Alzheimer disease (AD), but the diagnostic significance of cross-sectionally determined hippocampal volumes is still ambiguous. Diffusion-Tensor-Imaging (DTI) in MCI patients revealed an association of microstructural changes in hippocampal areas with verbal memory decline. MRI volumetry and DTI were combined to investigate 18 MCI patients attending a memory clinic, and 18 carefully age- and gender-matched healthy controls. Neuropsychological testing, high resolution T1-weighted volume MRI scans, and DTI scans with regions-of-interest in hippocampal areas were applied. Left hippocampal volume was significantly lower (-11%, P = 0.02) in MCI patients than in control subjects. No significant differences were found for the right hippocampus (-4%). Mean diffusivity (MD) was significantly elevated in MCI patients vs. controls in left (+10%, P = 0.002) and right hippocampal areas (+13%, P = 0.02). Hippocampal volume and MD values were not significantly correlated. Combining left hippocampal volume and MD measures showed that lower left hippocampal volumes were associated with poor verbal memory performance particularly when co-occurring with high MD values. No comparable associations could be found regarding the right hippocampal formation and with respect to non-verbal memory function. The results demonstrate that microstructural abnormalities as revealed by DTI are very sensitive early indicators of hippocampal dysfunction. The combination of macro- and microstructural parameters in hippocampal areas could be promising in early detection of neurodegenerative processes.