Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment.

OBJECTIVE: To test the hypothesis that depressive symptoms correlate with Alzheimer's disease (AD) type changes in CSF and structural and functional imaging including hippocampus volume, cortical thickness, white matter lesions, Diffusion tensor imaging (DTI), and fluoro-deoxy-glucose positron emission tomography (FDG-PET) in patient with subjective (SCI) and mild (MCI) cognitive impairment. METHOD: In 60 patients, depressive symptoms were assessed using the Geriatric Depression Scale. The subjects underwent MRI, 18F-FDG PET imaging, and lumbar CSF extraction. RESULTS: Subjects with depressive symptoms (n=24) did not have more pathological AD biomarkers than non-depressed. Uncorrected there were trends towards larger hippocampal volumes (P=0.06), less orbital WM damage measured by DTI (P=0.10), and higher orbital glucose metabolism (P=0.02) in the depressed group. The findings were similar when SCI and MCI were analyzed separately. Similarly, in patients with pathological CSF biomarkers (i.e., predementia AD, n=24), we found that correlations between scores on GDS and CSF Aß42 and P-tau indicated less severe AD-specific CSF changes with increasing depression. CONCLUSION: Depressive symptoms are common in SCI/MCI, but are not associated with pathological imaging or CSF biomarkers of AD. Depression can explain cognitive impairment in SCI/MCI or add to cognitive impairment leading to an earlier clinical investigation in predementia AD.

Multimodal imaging in mild cognitive impairment: Metabolism, morphometry and diffusion of the temporal-parietal memory network.

This study compared sensitivity of FDG-PET, MR morphometry, and diffusion tensor imaging (DTI) derived fractional anisotropy (FA) measures to diagnosis and memory function in mild cognitive impairment (MCI). Patients (n=44) and normal controls (NC, n=22) underwent FDG-PET and MRI scanning yielding measures of metabolism, morphometry and FA in nine temporal and parietal areas affected by Alzheimer's disease and involved in the episodic memory network. Patients also underwent memory testing (RAVLT). Logistic regression analysis yielded 100% diagnostic accuracy when all methods and ROIs were combined, but none of the variables then served as unique predictors. Within separate ROIs, diagnostic accuracy for the methods combined ranged from 65.6% (parahippocampal gyrus) to 73.4 (inferior parietal cortex). Morphometry predicted diagnostic group for most ROIs. PET and FA did not uniquely predict group, but a trend was seen for the precuneus metabolism. For the MCI group, stepwise regression analyses predicting memory scores were performed with the same methods and ROIs. Hippocampal volume and FA of the retrosplenial WM predicted learning, and hippocampal metabolism and parahippocampal cortical thickness predicted 5 minute recall. No variable predicted 30 minute recall independently of learning. In conclusion, higher diagnostic accuracy was achieved when multiple methods and ROIs were combined, but morphometry showed superior diagnostic sensitivity. Metabolism, morphometry and FA all uniquely explained memory performance, making a multi-modal approach superior. Memory variation in MCI is likely related to conversion risk, and the results indicate potential for improved predictive power by the use of multimodal imaging.

Morphometric changes in the episodic memory network and tau pathologic features correlate with memory performance in patients with mild cognitive impairment.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) may affect several cognitive domains, including attention and reasoning, but is often first characterized by memory deficits. The purpose of this study was to ask these 2 questions: 1) Can levels of CSF tau proteins and amyloid beta 42 peptide explain thinning of the cerebral cortex in patients with MCI? 2) How are brain morphometry, CSF biomarkers, and apolipoprotein E (APOE) allelic variation related to episodic memory function in MCI? MATERIALS AND METHODS: Hippocampal volume and cortical thickness were estimated by MR imaging and compared for patients with MCI (n = 18) and healthy controls (n = 18). In addition, regions of interest (ROIs) were selected in areas where the MCI group had atrophy and which overlapped with the episodic memory network (temporal, entorhinal, inferior parietal, precuneus/posterior cingulate, and frontal). Relationships among morphometry, CSF biomarkers, APOE, and memory were tested. The analyses were repeated with an independent sample of patients with MCI (n = 19). RESULTS: Patients with MCI and pathologic CSF values had hippocampal atrophy. However, both patients with pathologic and patients with nonpathologic CSF had a thinner cortex outside the hippocampal area. CSF pathology was related to hippocampal volume, whereas relationships with cortical thickness were found mainly in one of the samples. Morphometry correlated robustly with memory performance across MCI samples, whereas less stable results were found for tau protein. CONCLUSION: The differences in hippocampal volume between the MCI and the healthy control groups were only found in patients with pathologic CSF biomarkers, whereas differences in cortical thickness were also found for patients without such pathologic features. Morphometry in areas in the episodic memory network was robustly correlated with memory performance. It is speculated that atrophy in these areas may be associated with the memory problems seen in MCI.

Diaschisis after thalamic stroke: a comparison of metabolic and structural changes in a patient with amnesic syndrome.

INTRODUCTION: We present a patient with a left anteromedial thalamic lesion with an amnesic syndrome. The patient underwent neuropsychological testing, cerebrospinal fluid (CSF) analyses, magnetic resonance imaging (MRI) [T2, flair, and diffusion tensor imaging (DTI)] and [18F]-2-fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) to assess indirect effects of thalamic lesions on cortical function. CASE REPORT: A 67-year-old right-handed woman was admitted to a university-based memory unit because of memory and concentration problems. Neuropsychological testing revealed dysfunction of episodic memory, semantic memory and working memory. General intellectual function and attention capacity were preserved. MRI revealed an anteromedial thalamic lesion in the left hemisphere. FDG-PET showed decreased uptake in the frontal, parietal and temporal lobes of the left hemisphere. Regions of interest (ROI) in white matter were selected and left and right hemispheres were compared. Fractional anisotropy (FA) in ROI representing thalamo-cortical connections were decreased in the left hemisphere when compared with the right. CONCLUSION: The results show the importance of a network that include the anterior and dorsomedian nuclei, which influence the activity in areas of the cortex responsible for memory processes. The imaging findings suggest that areas of cortical diaschisis after thalamic infarction correspond to areas affected by thalamo-cortical fibre loss as measured with FA.