M N Rossor

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..CONCLUSIONS: The PSEN1 L153V mutation lies in the main mutation cluster of PSEN1 in the second transmembrane domain. It causes early-onset FAD with clinical features similar to those of other reported FAD pedigrees...

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..In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role...

..001). There was no correlation between age at disease onset, disease severity or length of illness. The increased concentration of CSF S100beta seen in frontotemporal dementia may reflect the marked astrocytosis seen in this condition...

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..Longitudinal MRI, neuropsychological and clinical data are presented over the decade preceding this man's diagnosis, through the asymptomatic and prodromal preludes to his presentation with MCI and on to eventual conversion to AD...

..This methodology whereby data from patients falling to floor on a given test may be included and accounted for, rather than discarded, may find broader application in clinical studies incorporating neuropsychometric outcomes...

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..CONCLUSIONS: Metabolic changes are detectable in presymptomatic mutation carriers years before expected onset of Alzheimer disease. Their magnitude is related to proximity of expected age at onset...

..The results also suggest that nominal function may be preserved in some cases with inherited prion disease...

..Screening for PSEN1 mutations may be appropriate in cases of familial dementia even where the clinical phenotype is not typical of AD...

..Fluid registered MRI may be a useful technique in assessing patterns of focal atrophy in vivo and demonstrating the progression of degenerative diseases...

..Increased rates of whole-brain atrophy did not discriminate AD from FTD, but analysis of regional atrophy rates revealed marked differences between patient groups...

..We used an imaging technique known as voxel-compression mapping to localise progressive atrophy in patients with preclinical Alzheimer's disease...

..To determine rates of cerebral atrophy in individuals with symptoms of memory loss but no objective cognitive impairment (SNCI) and their association with future cognitive decline...

..They are, however, consistent with the reported clinical phenotype in the majority of PSEN1 exon 6 mutations so far reported...

..We used automated cortical thickness (CTh) measurement to compare the grey matter of such a group with cognitively normal controls...

..This may have implications for the detection and treatment of Alzheimer's disease at an early stage...

..In neither disease did CSF tau correlate with disease severity as assessed by the Mini Mental State Examination score (MMSE). This study shows that CSF tau is significantly raised in patients with frontotemporal dementia...

..Two subtypes commonly present with a language disorder: semantic dementia (SemD) and progressive nonfluent aphasia (PNFA)...

..There was no significant difference in the severity of EEG abnormality between the FTLD and AD patient groups. These data suggest a need for reappraisal of the role of the EEG in the diagnostic differentiation of FTLD from AD...

..This study provides further evidence of the heterogeneity of the disease process...

..We suggest that although this finding may favor a diagnosis of dementia with Lewy bodies, it is not necessary for diagnosis...

..We conclude that sample sizes required in short interval therapeutic trials using cerebral atrophy as an outcome measure may be reduced if multiple serial MRI is performed...

..There may be a further genetic factor involved in the etiology of autosomal dominant early onset AD...

..We argue that cognitive and behavioural features in patients with brainstem lesions reflect remote effects of brainstem structures on frontal lobe and limbic regions, as a consequence of disruption to ascending neurotransmitter pathways...

..This review presents an approach to the diagnosis, investigation, and management of patients with young onset dementia, with particular reference to common and treatable causes...

..This study assessed the value of measuring MTR in addition to volumetric MR in differentiating patients with AD from control subjects...

..Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder...

..Scanning of asymptomatic at-risk individuals reveals a similar, but quantitatively less severe, pattern of hypometabolism...

..An EU-funded consortium has examined a retrospective series of neuropathologically confirmed Pick's disease cases to explore potential clinical diagnostic features. From these, draft clinical criteria have been developed...

..Significant resolution occurred once treatment was discontinued. Caution is required when prescribing memantine to patients with possible DLB...

..Reported are MRI findings of a Phase IIa immunotherapy trial in AD prematurely terminated owing to meningoencephalitis in a subset of patients...

..53, P<0.001). No such correlation was found for FTLD patients. This study supports the concept that S100B is of pathological relevance for degeneration of the central nervous system in AD...

..This cutoff level was confirmed in a prospective audit (n=100). As demand for CSF tau levels will increase globally, the accuracy of local CSF hTau cutoff levels can be compared against this benchmark...

..To determine the prevalence of dementia in people under the age of 65 in a large catchment area, and use these figures to estimate the number of younger people affected by dementia in the UK...

..CONCLUSION: A central immune response can occur in primary neurodegenerative dementias, albeit uncommonly...

..We suggest that neuroleptics should be used cautiously in FTLD and treatment should be started at low doses avoiding depot preparations until further prospective studies have been performed...

..MRI features described previously in PSP correspond to regions of pathological involvement demonstrated in separate studies, but serial MRI with pathological follow up has not been undertaken...

..Loss of cortical neurons is a key pathological feature in neurodegenerative dementias. Cerebrospinal fluid (CSF) neurofilaments (Nf) are a biomarker for neuronal death and axonal loss...

..Also, although plasma-derived SAP is always present in the cerebral and cerebrovascular amyloid lesions of AD, there was insufficient accumulation of injected labeled SAP to be detected by the present routine methodology...

..To describe the clinical features of nine British families with neuropathologically verified frontotemporal dementia (FTD) due to the intronic tau exon 10(+16) mutation...

..The magnitude of metabolite abnormalities in the thalami in moderately advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols allow the measurement of MI, which adds discriminant power to the MRS examination...

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..CONCLUSIONS: These findings suggest that, although not the presenting feature, mild cognitive decline may be evident in the early stages of CJD associated with human cadaveric growth hormone treatment...

..In this review we discuss some historical aspects surrounding these reflexes, how they might be elicited and interpreted, and their potential clinical utility in modern neurological practice...

..Furthermore, these data suggest that there are at least 2 additional genes to be identified among families with autosomal dominant FTD...

..This has implications where shorter inter-scan intervals may be advantageous, such as rapid diagnosis, and tracking of disease progression including in a clinical trial...

..This study shows that familial FTDU has profound focal neuronal loss in multiple association areas that relate to the clinical symptoms characteristic of the disease...

..Our results suggest that PS-1 mutations affect cerebral accumulation of Abeta burden in a different fashion from APP717 mutations in their familial AD brains...

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..The SNCI group may represent a heterogeneous group with some individuals in the early stages of AD whilst others' memory complaints are more likely linked to anxiety or personality traits...

..Therefore in our brain bank series of frontotemporal degeneration, most cases were non-tauopathies with FTLD-U accounting for 62% of all the diagnoses...

..The clinical course of PLOSL has not been characterized in a series of patients with TREM2 mutations...

..This potential benefit must be balanced against the possibility that ventricular volumes may be more likely to be affected by factors other than neurodegeneration...

..By exon trapping, the mutation produced an increase in the splicing in of exon 10, indicating that it probably causes disease through an overproduction of four-repeat tau...

..Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome...

..This suggests that usually FTDP-17 and PSP, including the rare familial form of PSP, are likely to be separate conditions and that usually PSP and typical PSP-like syndromes are not due to mutations in tau...

..Another affected sibling also had MRI white matter abnormalities. The MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels...

..I143F shows incomplete penetration within the affected family. P436S is the most carboxy-terminal presenilin 1 mutation reported to date...

..There was no difference between the tau H2 haplotype or H2H2 genotype frequency in PiD cases and control subjects. No tau mutations were identified in pathologically typical cases of PiD, with antibody 12-E8-negative Pick bodies...

..We discuss this issue using three illustrative cases...

..An increasing number of recently described tau mutations show considerable clinical heterogeneity. The assessment of this phenotypic variation is of vital importance in the differential diagnosis of neurodegenerative diseases...

..05 > CI 95% > 1.85]). CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype...

..The APPAla692Gly (Flemish) mutation was reported in a family in which affected members developed hemorrhagic stroke, progressive dementia, or both...