Ingrid Schermuly

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 Alzheimers 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 (Spearmans rho=0.81, P=0.001). Moreover, Boston naming test performance also correlated with the left cingulate bundle integrity (Spearmans 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.

Voxel-based analyses of diffusion-tensor imaging in Fabry disease

Background: Fabry disease (FD) is a lysosomal storage disorder associated with marked cerebrovascular disease. Conventional MRI shows an extensive load of white matter lesions (WMLs) which may already be present at an early stage in the disease. Objective: Investigator independent and sensitive quantification of structural changes in the brain in clinically affected men and women with FD. Methods: We performed a voxel based analysis of diffusion tensor images (DTI) in 25 patients with FD and 20 age matched normal controls. Results: DTI revealed significant increases in cerebral white matter mean diffusivity (MD) in patients with FD, which were pronounced in the periventricular white matter. Even the subgroup of patients without significant WMLs load (n = 18) showed increased diffusivity in the cerebral white matter. In gray matter areas, MD elevation was detected only in the posterior part of the thalamus, independent of the visible pulvinar alterations on T1 weighted images. Voxel based fractional anisotropy measurements did not differ significantly between patients and controls. Conclusions: The present study demonstrates the clinical feasibility of voxel based analysis of DTI as a sensitive tool to quantify brain tissue alterations in FD. The pattern of increased brain tissue diffusivity is probably due to microangiopathic alterations, mainly affecting the long perforating arteries.

State dependent posterior hippocampal volume increases in patients with major depressive disorder

BACKGROUND The hippocampal formation has been implicated in etiology and therapy response in major depressive disorder (MDD). However, prospective longitudinal studies investigating volumes in hippocampal subregions and their association with clinical findings are still lacking. METHODS Global and regional hippocampal volumes and neuropsychological performance were assessed longitudinally in 15 young patients with unipolar early onset MDD who responded to therapy and 13 matched healthy control subjects. RESULTS Although volumes at baseline did not differ between groups, patients with MDD showed significant posterior hippocampal volume increases during the treatment course (mean observation period 161.4 ± 58.6 days). Posterior hippocampal volume increases were seen in every single patient. The detected posterior hippocampal volume increases were significantly correlated with the number of solved problems in a planning task at baseline. LIMITATIONS The study is limited by the small sample size. Moreover, future studies should include patients who do not respond to antidepressant treatment. CONCLUSION Patients with MDD showed selective increases in posterior hippocampal volumes which were not correlated to the degree of functional restitution. However, posterior hippocampal volume increases might constitute a surrogate parameter of neuroplasticity taking place during antidepressant therapy which might be predicted by executive functioning at baseline.

Automated tractography of the cingulate bundle in Alzheimer's disease: A multicenter DTI study

To evaluate the feasibility of multicenter tractography of the cingulate bundle (CB) in Alzheimers disease (AD).

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 Alzheimers 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.

Structural integrity of the corpus callosum predicts long‐term transfer of fluid intelligence‐related training gains in normal aging

Although cognitive training usually improves cognitive test performance, the capability to transfer these training gains into respective or functionally related cognitive domains varies significantly. Since most studies demonstrate rather limited transfer effects in older adults, aging might be an important factor in transfer capability differences. This study investigated the transfer capability of logical reasoning training gains to a measure of Fluid Intelligence (Gf) in relation to age, general intelligence, and brain structural integrity as measured by diffusion tensor imaging. In a group of 41 highly educated healthy elderly, 71% demonstrated successful transfer immediately after a 4‐week training session (i.e. short‐term transfer). In a subgroup of 22% of subjects transfer maintained over a 3‐month follow‐up period (i.e. long‐term transfer). While short‐term transfer was not related to structural integrity, long‐term transfer was associated with increased structural integrity in corpus and genu of the corpus callosum. Since callosal structural integrity was also related to age (in the present and foregoing studies), previously observed associations between age and transfer might be moderated by the structural integrity. Surprisingly, age was not directly associated with transfer in this study which could be explained by the multi‐dependency of the structural integrity (modulating factors beside age, e.g. genetics). In this highly educated sample, general intelligence was not related to transfer suggesting that high intelligence is not sufficient for transfer in normal aging. Further studies are needed to reveal the interaction of transfer, age, and structural integrity and delineate mechanisms of age‐dependent transfer capabilities. Hum Brain Mapp 35:309–318, 2014.

Quantification of brain tissue alterations in Fabry disease using diffusion‐tensor imaging

Central nervous system involvement is a major burden in Fabry disease. Conventional cranial magnetic resonance imaging (MRI) shows micro‐ and macroangiopathic changes such as severe and progressive white matter lesions (WMLs) at an early age on T2‐ and fluid‐attenuated inversion recovery‐weighted images, increased signal intensity in the pulvinar on T1‐weighted MRI, as well as tortuosity and dilatation of the larger vessels (dolicho‐ectasia). Using diffusion tensor imaging (DTI), a new structural MRI‐technique that measures water diffusion characteristics, we showed marked brain tissue alterations in Fabry disease predominantly in the periventricular white matter. Even patients with few WMLs had significantly elevated brain tissue diffusivity.

Quality of Life in Dementia: Impact of Cognition and Insight on Applicability of the SF-36

OBJECTIVES Comparability of measures of quality of life in dementia and in other diagnostic groups, such as mild cognitive impairment, normal aging, or other diseases, is highly desirable. However, the impact of cognitive deficits and impaired insight on applicability and validity of generic instruments is sparsely studied. PARTICIPANTS AND MEASUREMENTS Sixty patients with dementia [38 women; age: mean (SD) = 78.7 (6.4) years; Mini-Mental State Examination (MMSE): mean (SD) = 20.2 (6.0)] recruited as part of the start-modem study, a multicenter care research study in Germany, completed the generic instrument SF-36 and the specific instrument Quality of Life-Alzheimers Disease (QOL-AD). RESULTS QOL-AD self-rating scores [mean (SD) = 32.8 (5.9)] and SF-36 subscales indicated moderate to good quality of life in the total group. Reliability and validity of five subdomains of the SF-36 were poor in subgroups of patients with impaired insight or with MMSE scores less than 17 (Cronbachs α <0.7, no significant correlation to the QOL-AD). In contrast, for patients with both adequate insight and MMSE score greater than 16 (n = 33; 55%) Cronbachs α of the subdomains of the SF-36 ranged between 0.920 and 0.676. Seven of the eight subdomains correlated significantly with the QOL-AD self-rating and composite score in this group of patients (0.355 ≤ r ≤ 0.709). CONCLUSIONS Despite the impact of insight and cognition on self-rated quality of life, we found reliable and valid data for a broad spectrum of patients with dementia. According to the present data, the SF-36 is suitable for dementia patients with both insight into their deficits and an MMSE score greater than 16.

Multi-center DTI tractography of the cingulate bundle in Alzheimer's disease: A study of accuracy and comparability

CINGULATE BUNDLE IN ALZHEIMER’S DISEASE: A STUDY OFACCURACYAND COMPARABILITY Florian Fischer, Armin Scheurich, MartinWegrzyn, Ingrid Schermuly, Arun Bokde, Stefan Kl€oppel, Petra J.W. Pouwels, Stefan Teipel, Igor Yakushev, Andreas Fellgiebel, University Medical Center Mainz, Mainz, Germany; German Center for Neurodegenerative Diseases, Rostock, Germany, Rostock, Germany; Trinity College Dublin, Dublin, Ireland; 4 University Medical Center Freiburg, Freiburg, Germany; 5 VU University Medical Center, Amsterdam, Netherlands; 6 Department of Psychiatry, University of Rostock, Rostock, Germany.