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As a characteristic feature of Alzheimer's disease (AD) hippocampal atrophy (HA) can be demonstrated in the majority of patients by using neuroimaging techniques in particular magnetic resonance imaging (MRI). Hippocampal atrophy is associated with declarative memory deficits and can also be associated with changes of adjacent medial temporal substructures such as the parahippocampal gyrus or the the entorhinal cortex. Similar findings are present in patients with mild cognitive impairment (MCI) albeit to a lesser extent. While these finding facilitate the diagnostic process in patients with clinical suspicious AD, the metric properties of hippocampal atrophy for delineating healthy aging from MCI and mild AD still appear to be rather limited; as such it is not sufficient to establish the diagnosis of AD (and even more so of MCI). This limitation partly refers to methodological issues and partly to the fact that hippocampal tissue integrity is subject to various pathogenetic influences other than AD. Moreover,the effects of hippocampal atrophy on the behavioral level (e.g. cognitive deficits) are modulated by the individual's cognitive reserve. From a clinical standpoint these observations are in line with the hypothesis that the onset and course of AD is influenced by a number of peristatic factors which are partly conceptualized in the concepts of brain and/or cognitive reserve. These complex interactions have to be considered when using the presence of hippocampal atrophy in the routine diagnostic procedure of AD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance., Methods: Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T., Results: The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001)., Conclusions: The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

We tested the effects of variation of stimulus onset asynchrony (SOA) on visual working memory (WM) performance across different load levels and the underlying brain activation patterns using functional magnetic resonance imaging (fMRI) in 48 healthy participants. Participants were instructed to memorise arrays of coloured squares and had to perform a match/non-match judgement on a probe stimulus after a jittered delay. We presented visual pattern masks at four SOAs after the offset of the memory array (100 ms, 200 ms, 400 ms, and 800 ms). Memory performance decreased with increased load and shortened SOA. Brain activation data showed significant effects of load (during encoding and retrieval), SOA (retrieval) and an interaction of load by SOA (encoding), mainly in frontal and parietal areas. There was also a direct relationship between successfully stored items and activation in the right inferior parietal lobule and the left middle frontal gyrus. The neurobehavioral results suggest that the frontal regions, together with the inferior parietal lobe, are associated with successful WM performance, especially under the most challenging conditions of high load and short SOAs., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Episodic memory dysfunction, commonly assessed with word list recall, is the main characteristic of amnestic Mild Cognitive Impairment (aMCI). While brain pathology underlying this kind of memory impairment is well established in aMCI, little is known about the effect of neurodegeneration on autobiographical memory. The present study investigated neuronal correlates of autobiographical memory in aMCI patients (n=12) and healthy elderly controls (n=13) using functional magnetic resonance imaging (fMRI). Additionally, voxel-based morphometry (VBM) was employed to reveal brain pathology in aMCI patients. Neuropsychological assessment showed significant impairment in episodic memory tasks (immediate and delayed word list recall) in aMCI patients. Moreover, VBM revealed significantly reduced gray matter concentration, which was most pronounced in the temporal lobes of aMCI patients. Despite episodic memory impairment and atrophy in areas that are associated with encoding and recall of episodic memories, aMCI patients showed no alterations in brain activation associated with autobiographical memory retrieval. These findings could suggest that autobiographical memory is subserved by a different neuronal network than episodic memory and that the two memory systems are differently affected by aMCI., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Manual segmentation from magnetic resonance imaging (MR) is the gold standard for evaluating hippocampal atrophy in Alzheimer's disease (AD). Nonetheless, different segmentation protocols provide up to 2.5-fold volume differences. Here we surveyed the most frequently used segmentation protocols in the AD literature as a preliminary step for international harmonization. The anatomical landmarks (anteriormost and posteriormost slices, superior, inferior, medial, and lateral borders) were identified from 12 published protocols for hippocampal manual segmentation ([Abbreviation] first author, publication year: [B] Bartzokis, 1998; [C] Convit, 1997; [dTM] deToledo-Morrell, 2004; [H] Haller, 1997; [J] Jack, 1994; [K] Killiany, 1993; [L] Lehericy, 1994; [M] Malykhin, 2007; [Pa] Pantel, 2000; [Pr] Pruessner, 2000; [S] Soininen, 1994; [W] Watson, 1992). The hippocampi of one healthy control and one AD patient taken from the 1.5T MR ADNI database were segmented by a single rater according to each protocol. The accuracy of the protocols' interpretation and translation into practice was checked with lead authors of protocols through individual interactive web conferences. Semantically harmonized landmarks and differences were then extracted, regarding: (a) the posteriormost slice, protocol [B] being the most restrictive, and [H, M, Pa, Pr, S] the most inclusive; (b) inclusion [C, dTM, J, L, M, Pr, W] or exclusion [B, H, K, Pa, S] of alveus/fimbria; (c) separation from the parahippocampal gyrus, [C] being the most restrictive, [B, dTM, H, J, Pa, S] the most inclusive. There were no substantial differences in the definition of the anteriormost slice. This survey will allow us to operationalize differences among protocols into tracing units, measure their impact on the repeatability and diagnostic accuracy of manual hippocampal segmentation, and finally develop a harmonized protocol.

Magnetic resonance imaging (MRI)-based volumetry of medial temporal lobe regions is among the best established biomarker candidates of Alzheimer's disease (AD) to date. This study assessed the effect of multicentre variability of MRI-based hippocampus and amygdala volumetry on the discrimination between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and on the association of morphological changes with ApoE4 genotype and cognition. We studied 113 patients with clinically probable AD and 150 patients with amnestic MCI using high-resolution MRI scans obtained at 12 clinical sites. We determined effect sizes of group discrimination and random effects linear models, considering multicentre variability. Hippocampus and amygdala volumes were significantly reduced in AD compared with MCI patients using data pooled across centres. Multicentre variability did not significantly affect the power to detect a volume difference between AD and MCI patients. Among cognitive measures, delayed recall of verbal and non-verbal material was significantly correlated with hippocampus and amygdala volumes. Amygdala and hippocampus volumes were not associated with ApoE4 genotype in AD or MCI. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for cross-sectional diagnostic studies, and they replicate essential findings from smaller scale monocentre studies.

Purpose: Objective quantification of brain structure can aid diagnosis and therapeutic monitoring in several neuropsychiatric disorders. In this study, we aimed to compare direct and indirect quantification approaches for hippocampal formation changes in patients with mild cognitive impairment and Alzheimer's disease (AD)., Methods and Materials: Twenty-one healthy volunteers (mean age: 66.2), 21 patients with mild cognitive impairment (mean age: 66.6), and 10 patients with AD (mean age: 65.1) were enrolled. All subjects underwent extensive neuropsychological testing and were imaged at 1.5T (Vision, Siemens, Germany; T1w coronal TR=4 ms, Flip=13 degrees , FOV=250 mm, Matrix=256 x 256, 128 contiguous slices, 1.8mm). Direct measurement of the hippocampal formation was performed on coronal slices using a standardized protocol, while indirect temporal horn volume (THV) was calculated using a watershed algorithm-based software package (MeVis, Germany). Manual tracing took about 30 min, semi-automated measurement less than 3 min time., Results: Successful direct and indirect quantification was performed in all subjects. A significant volume difference was found between controls and AD patients (p<0.001) with both the manual and the semi-automated approach. Group analysis showed a slight but not significant decrease of hippocampal volume and increase in temporal horn volume (THV) for subjects with mild cognitive impairment compared to volunteers (p<0.07). A significant correlation (p<0.001) of direct and indirect measurement was found., Conclusion: The presented indirect approach for hippocampus volumetry is equivalent to the direct approach and offers the advantages of observer independency, time reduction and thus usefulness for clinical routine.

Recent studies indicate that morphological and functional abnormalities of the cerebellum are associated with schizophrenia. Since the cerebellum is crucial for motor coordination, one may ask whether the respective changes are associated with motor dysfunction in the disease. To test these hypotheses in a clinical study, we investigated cerebellar volumes derived from volumetric magnetic resonance imaging of 37 first-episode patients with schizophrenia, schizophreniform or schizoaffective disorder and 18 healthy controls matched for age, gender and handedness. To control for potential interindividual differences in head size, intracranial volume was entered as a covariate. Neurological soft signs (NSS) were examined after remission of acute symptoms. Compared with the controls, patients had significantly smaller cerebellar volumes for both hemispheres. Furthermore, NSS in patients were inversely correlated with tissue volume of the right cerebellar hemisphere partialling for intracranial volume. No associations were detected between cerebellar volumes and psychopathological measures obtained at hospital admission when patients were in the acute psychotic state or after remission, treatment duration until remission, treatment response or prognostic factors, respectively. These findings support the hypothesis of cerebellar involvement in schizophrenia and indicate that the respective changes are associated with NSS.

ObjectiveThe pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).MethodsTemporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aβ, and tau burden for each hippocampal subfield were obtained.ResultsWe found significant correlations between hippocampal volume and Braak and Braak staging (ρ = -0.75, P = .001), tau (ρ = -0.53, P = .034), Aβ burden (ρ = -0.61, P = .012), and neuronal count (ρ = 0.77, P < .001). Exploratory subfield-wise significant associations were found for Aβ in Cornu Ammonis (CA)1 (ρ = -0.58, P = .019) and subiculum (ρ = -0.75, P = .001), tau in CA2 (ρ = -0.59, P = .016), and CA3 (ρ = -0.5, P = .047), and neuronal count in CA1 (ρ = 0.55, P = .028), CA3 (ρ = 0.65, P = .006), and CA4 (ρ = 0.76, P = .001).ConclusionsThe observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.

Background: Alzheimer's disease (AD) pathology is present many years before the onset of clinical symptoms. AD dementia cannot be treated. Timely and early detection of people at risk of developing AD is key for primary and secondary prevention. Moreover, understanding the underlying pathology that is present in the earliest stages of AD, and the genetic predisposition to that might contribute to the development of targeted disease-modifying treatments. Objectives: In this study, we aimed to explore whether genetic disposition to AD in asymptomatic individuals is associated with altered intrinsic functional connectivity as well as cognitive performance on neuropsychological tests. Methods: We examined 136 cognitively healthy adults (old group: mean age = 69.32, SD = 4.23; young group: mean age = 31.34, SD = 13.12). All participants had undergone resting-state functional magnetic resonance imagining (fMRI), DNA genotyping to ascertain polygenic risk scores (PRS), and neuropsychological testing for global cognition, working memory, verbal fluency, and executive functions. Results: Two-step hierarchical regression analysis revealed that higher PRS was significantly associated with lower scores in working memory tasks [Letter Number Span: Δ R 2 = 0.077 (p < 0.05); Spatial Span: Δ R 2 = 0.072 (p < 0.05)] in older adults (>60 years). PRS did not show significant modulations of the intrinsic functional connectivity of the posterior cingulate cortex (PCC) with other regions of interest in the brain that are affected in AD. Conclusion: Allele polymorphisms may modify the effect of other AD risk factors. This potential modulation warrants further investigations, particularly in cognitively healthy adults. [ABSTRACT FROM AUTHOR]

Background: Dietary lipids (omega-3 polyunsaturated fatty acids (n-3) PUFAs) and saturated fatty acids (SFA) seem to play an important role in brain health. (n-3) PUFAs have been shown to improve cerebral perfusion and to promote synaptogenesis. In this study, we investigated the relationship between dietary fat composition, cognitive performance and brain morphology in cognitively healthy individuals. Methods: A total of 101 cognitively healthy participants (age: 42.3 ± 21.3 years, 62 females) were included in this study. Verbal memory was assessed using the California Verbal Learning Test (CVLT). Intake of (n-3) PUFA and SFA was calculated from food-frequency questionnaire-derived data (EPIC-FFQ). Magnetic resonance imaging (MRI) data were obtained (Siemens Trio 3T scanner) and grey matter volumes (GMV) were assessed by voxel-based morphometry (VBM/SPM8). We examined the association of SFA/(n-3) PUFA ratio and memory performance as well as GMV using regression models adjusted for age, sex, education, body mass index, apolipoprotein E (APOE) status and alcohol consumption. For VBM data, a multiple regression analysis was performed using the same covariates as mentioned before with intracranial volume as an additional covariate. Results: A high SFA/(n-3) PUFA ratio was significantly (p < 0.05) correlated with poorer verbal memory performance and with lower GMV in areas of the left prefrontal cortex that support memory processes. Conclusions: These findings suggest that a diet rich in PUFAs is likely to exert favourable effects on brain morphology in brain areas important for memory and executive functions. This could constitute a possible mechanism for maintaining cognitive health in older age. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) often precedes Alzheimer's Dementia (AD), and in a high proportion of individuals affected by MCI, there are already neuropathological processes ongoing that become more evident when patients progress to AD. Accordingly, there is a need for reliable biomarkers to distinguish between normal aging and incipient AD. Recent research suggests that, in addition to established biomarkers such as CSF Aß42, total tau and hyperphosphorylated tau, resting state connectivity established by functional magnetic resonance imaging might also be a feasible biomarker for prodromal stages of AD. In order to explore this possibility, we investigated resting state functional connectivity as well as cerebrospinal fluid (CSF) biomarker profiles in patients with MCI (n = 30; age 66.43 ± 7.06 years) and cognitively healthy controls (n = 38; age 66.89 ± 7.12 years). CSF Aß42, total tau and hyperphosphorylated tau concentrations were correlated with measures of cognitive performance (immediate and delayed recall, global cognition, processing speed). Moreover, MCI-related alterations in intrinsic functional connectivity within the default mode network were investigated using functional resting state MRI. As expected, MCI patients showed decreased CSF Aß42 and increased total tau concentrations. These alterations were associated with cognitive performance. However, there were no differences between MCI patients and cognitively healthy controls regarding intrinsic functional connectivity. In conclusion, our results indicate that CSF protein profiles seem to be more closely related to cognitive decline than alterations in resting state activity. Thus, resting state connectivity might not be a reliable biomarker for early stages of AD. [ABSTRACT FROM AUTHOR]

Exercise has been shown to counteract age‐related volume decreases in the human brain, and in this imaging study, we ask whether the same holds true for the microstructure of the cortex. Healthy older adults (n = 47, 65–90 years old) either exercised three times a week on a stationary bike or maintained their usual physical routine over a 12‐week period. Quantitative longitudinal relaxation rate (R1) magnetic resonance imaging (MRI) maps were made at baseline and after the 12‐week intervention. R1 is commonly taken to reflect cortical myelin density. The change in R1 (ΔR1) was significantly increased in a region of interest (ROI) in the primary motor cortex containing motor outputs to the leg musculature in the exercise group relative to the control group (p =.04). The change in R1 in this ROI correlated with an increase in oxygen consumption at the first ventilatory threshold (VT1) (p =.04), a marker of improvement in submaximal aerobic performance. An exploratory analysis across the cortex suggested that the correlation was predominately confined to the leg representation in the motor cortex. This study suggests that microstructural declines in the cortex of older adults may be staved off by exercise. [ABSTRACT FROM AUTHOR]

The apolipoprotein E (ApoE) ɛ4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ4 carriers. The increased BOLD response in old ɛ4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age. [ABSTRACT FROM AUTHOR]

Background: Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear. Objective: We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI). Design: In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n = 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure. Results: MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P = 0.014) and recognition performance (P = 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P = 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects. Conclusions: Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. [ABSTRACT FROM AUTHOR]

Introduction: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer's disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD. Methods: WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE Ɛ4 risk allele) was determined globally as well as regionally with voxelbased lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network. Results: WM hyperintensity volume was significantly greater in non-carriers of the APOE Ɛ4 allele. Lesion distribution was similar among Ɛ4 carriers and non-carriers. Only Ɛ4 non-carriers showed a correlation between lesion volume and cognitive performance. Conclusion: The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE Ɛ4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE Ɛ4-mediated risk. [ABSTRACT FROM AUTHOR]

Background: The E4 isoform of the APOE genotype is the most significant genetic risk factor for sporadic Alzheimer's disease (AD) and has recently been found to modulate disease expression in patients with AD. Objective: To investigate APOE-dependent cognitive and structural phenotypes in subjects with mild cognitive impairment who converted to AD within the following three years. Methods: Subjects converting to AD (n = 63) were compared to a control group with stable mild cognitive impairment (n = 131). Clinical, neuropsychological, and MRI data were obtained by the German Dementia Competence Network. Subgroups of converting and stable APOE E4 carriers and non-carriers were investigated longitudinally with MRI to examine structural correlates of conversion. Voxel-based morphometry was applied to investigate gray matter distribution. Results: At baseline, executive performance correlated with global and bilateral prefrontal gray matter volume and predicted conversion only among non-carriers. Converting carriers and non-carriers presented distinct patterns of brain atrophy on longitudinal analysis, in line with a dissociation between more pronounced occipital atrophy in carriers and more frontoparietal volume loss in non-carriers at follow-up. Conclusions: The current findings suggest that in APOE E4 non-carriers with AD, executive dysfunction is closely linked to frontal gray matter atrophy and predictive of progression to dementia. The results are consistent with APOE genotype-dependent profiles of structural damage and cognitive decline in patients with imminent conversion to AD. [ABSTRACT FROM AUTHOR]

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Abstract: Background: There are many studies on life events in depression and also several studies examining brain structural changes in the hippocampus of depressed patients. However, only few studies have focused on the association of life events and hippocampal volume in depression. The hypothesis of a significant negative association between life events and hippocampal volumes in first episode depression was examined. Methods: 28 in-patients with a first episode of major depression were examined with high-resolution magnetic resonance imaging measuring hippocampal volumes. The precourse of depression was assessed with the Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses (IRAOS) and life events by using the Munich Interview for the Assessment of Life Events and Conditions (MEL). Results: A significant negative correlation between major life events three month before the onset of depression and the left hippocampal volume was found for male patients. In female patients no significant association between major life events and hippocampal volumes could be found. Conclusions: The results support the hypothesis that the hippocampus plays a crucial role in the pathogenesis of major depression in the early phase of the disorder particularly for male patients. [Copyright &y& Elsevier]

Background: Although previous studies demonstrate significant atrophy of the corpus callosum (CC) in patients with Alzheimer’s disease (AD), CC alterations in mild cognitive impairment have not been investigated yet. Methods: 21 subjects with mild cognitive impairment, 10 with AD and 21 healthy controls were investigated using magnetic resonance imaging. In the mid-sagittal slice the CC was traced manually. Additionally, voxel-based morphometry (VBM) was performed. Results: The CC was significantly smaller in patients with AD compared to healthy controls in both manual tracing and VBM. The atrophy was prominent in rostral parts of the CC. In subjects with mild cognitive impairment, the two rostral CC segments were smaller compared to controls when manually traced. In contrast, VBM revealed no significant difference between subjects with mild cognitive impairment and controls. Conclusion: Manual tracing was more sensitive in detecting discrete structural CC changes than VBM. Alterations of the CC in mild cognitive impairment rank in between normal aging and AD, supporting the hypothesis that mild cognitive impairment most often represents a preclinical stage of AD. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Neuropsychological deficits were investigated with respect to regional distribution of cerebral atrophy as assessed by volumetric magnetic resonance imaging (MRI) in 50 patients with Alzheimer''s dementia (AD; NINCDS-ADRDA criteria) and 20 healthy volunteers. When compared between groups, test performance of all investigated neuropsychological domains including declarative memory, language, praxia, psychomotor speed, as well as attention and concentration was significantly impaired. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala–hippocampus complex correlated with declarative memory performance, whereas volumes of the left temporo-parietal regions correlated with performance in naming and praxia. Furthermore, left frontal lobe atrophy was associated with verbal fluency. Our data confirm the central role that medial temporal atrophy plays for declarative memory deficits in AD and indicate that additional changes in the parietal, temporal and frontal lobes are responsible for further neuropsychological deficits characteristic of this disorder. [Copyright &y& Elsevier]

Increased tau levels are a well-established finding in Alzheimer''s disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables, type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset. [Copyright &y& Elsevier]

Although the hippocampus has been found to be smaller in people with depression, the clinical relevance of this is unclear. We investigated hippocampal volume (using high-resolution magnetic resonance imaging) and 2-year outcome in 57 patients with major depression. The left and right hippocampal volumes of patients with a depression relapse were significantly smaller than those of healthy controls. Our results support the hypothesis that the hippocampus is crucial in the outcome of depression. [ABSTRACT FROM AUTHOR]