A visual [18F]FDG-PET rating scale for the differential diagnosis of frontotemporal lobar degeneration.

This study presents a visual rating scale for the assessment of cerebral [(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) scans to characterize typical findings in dementias associated with frontotemporal lobar degeneration (FTLD) and to differentiate individual patients with FTLD compared to Alzheimer's disease (AD) and mild cognitive impairment (MCI). A total of 43 cerebral PET scans from patients with FTLD (n = 16, mean age 58.4 years), AD (n = 16, 59.9 years) and MCI (n = 11, 57.9 years) were analysed. Every PET data set was visually rated for seven brain regions on each hemisphere (frontal lobe, temporal lobe, parietal lobe, occipital lobe, basal ganglia, thalamus and cerebellum). The extent of the impairment in metabolism was classified as absent, mild, medium or strong. Using this four-stage visual rating scale, characteristic profiles of metabolic impairment in FTLD, AD, MCI and the FTLD-subgroup FTD (n = 9) could be demonstrated. Patients with FTLD showed a significantly lower metabolism in the left frontal lobe and in the left basal ganglia when compared to AD and to MCI. Complementary analyses using statistical parametric mapping (SPM2) supported the findings of the visual analysis. In detecting FTLD with visual rating, sensitivity/specificity was 81/94% compared to AD and 81/64% compared to MCI. Patients with FTD were correctly attributed to a diagnosis of FTLD with a sensitivity of 89%. This visual rating scale may facilitate the differential diagnosis of FTLD in clinical routine.

Memory performance correlates with gray matter density in the ento-/perirhinal cortex and posterior hippocampus in patients with mild cognitive impairment and healthy controls--a voxel based morphometry study.

Voxel based morphometry (VBM) is a useful tool to assess differences in brain morphology between groups of patients and healthy controls. In addition, VBM enables the performance of regression analyses to determine potential correlations between performance on cognitive tests and variations in local brain morphology. Prior VBM studies investigating patients with mild cognitive impairment (MCI) have revealed different patterns of local brain atrophy. In order to extend previous findings, we investigated 18 patients with MCI and 18 age- and gender-matched healthy controls. All participants underwent extensive neuropsychological testing in addition to undergoing anatomical scanning with magnetic resonance imaging (MRI). Cohort analysis revealed bilateral decreases in gray matter density in the medial temporal lobes (MTLs) and neocortical regions of the temporal lobes in patients with MCI. Moreover, regression analyses demonstrated a correlation between immediate verbal recall and gray matter density in the left perirhinal/entorhinal cortex, while delayed free recall correlated with gray matter density in the left hippocampus. It has been proposed that performance in the immediate recall is supported by the so-called "episodic buffer", a component of working memory that contributes to the maintenance of integrated memory traces. Accordingly, our results suggest that anatomical regions associated with verbal long-term and verbal working memory are structurally segregated within the left MTL.

Cerebrospinal fluid tau and beta-amyloid in Alzheimer patients, disease controls and an age-matched random sample.

We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)-beta-amyloid1-42 (Abeta42), -total-tau (tau) and -phosphorylated-tau181 (p-tau181) as measured by sandwich ELISAs in the clinical routine of a community state hospital to discriminate between patients with Alzheimer's disease (AD), healthy controls (HC), non-AD-dementias, a group composed of various psychiatric disorders (non-AD-dementias, mental diseases) and an age-matched random sample (RS) (total N=219). By comparing patients with AD to HC as reference, tau revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau(181) 88%/80%, tau/Abeta42-ratio 81%/85% and phospho-tau(181)/Abeta42-ratio 81%/78%. Discriminative power between HC and all dementias under investigation was estimated lower for tau (78%/77%) and p-tau(181) (73%/79%). Relative to patients with AD, ROC analysis for the RS revealed highest sens/spec for p-tau181 (79%/77%) and p-tau181/Abeta42 ratio (78%/75%). Differentiation between AD versus a group made of patients with various psychiatric disorders was optimised by using CSF-p-tau181 (80%/77%). Under clinical routine conditions current CSF-biomarkers show a substantial capacity to discriminate between AD and HC as reference and to mark off AD patients from RS and heterogeneous diagnostic groups composed of non-AD dementias and other psychiatric conditions. Despite a residual substantial overlap between the groups, we conclude that current CSF markers are well suited to support AD-related diagnostic procedures in every-day clinics.

[Genetic tau-variants in patients with frontotemporal dementia]. / Tau-assoziierte genetische Polymorphismen bei frontotemporaler Demenz.

OBJECTIVE: [corrected] To evaluate tau-associated genetic polymorphisms in patients with sporadic frontotemporal dementia (FTD) and healthy control subjects. METHOD: Tau-gene sequence of 30 patients with FTD and 30 healthy controls was analysed by polymerase-chain-reaction (PCR). Subsequent sequencing was performed to identify exonic and intronic differences between both groups. RESULTS: The following polypmorphisms, which are localized closely to each exon-intron-border, have been identified: In 37 % (n = 11) of the control subjects three different intronic polymorphisms occur simultaneously (Intron 2, 263, C --> Y; Intron 3, 590, A --> R; Intron 11, 150, G --> A). In the FTD group, this coexistance has been observed only in 17 % (n = 5). CONCLUSIONS: In how far there exists a significant correlation between the newly identified triple polymorphism in the Tau gene and an alternated risk for FTD must be evaluated in a lager population. The proximity of these polymorphisms to the exon-intron border would facilitate functional influences on gene expression patterns. These preliminary results described, above potentially point to further pathogenetic factors in the genesis of FTD.

[Differences in cerebral glucose metabolism between frontotemporal lobar degeneration and Alzheimer's disease]. / Unterschiede im zerebralen Glukosestoffwechsel zwischen frontotemporaler lobärer Degeneration und der Alzheimer-Krankheit.

OBJECTIVE: To describe differences in cerebral glucose metabolism between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). METHODS: 14 patients with FTLD (7 f/7 m, mean age 60.1 years) and 14 patients with AD (7 f/7 m, mean age 59.5 years) were examined. [18F]FDG positron emission tomography (PET) scans were analysed with statistical nonparametric mapping (SnPM) and statistical parametric mapping (SPM99). RESULTS: Significant decreases in glucose metabolism in FTLD compared to AD were detected in the left insula/left inferior frontal gyrus (Brodman area [BA]13, 45 and 47) and in the medial frontal gyrus bilaterally (BA10). A significant decrease in AD compared to FTLD was identified in the right middle temporal gyrus (BA39). CONCLUSION: Cerebral PET could be a promising tool to discriminate FTLD from AD.