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OBJECTIVE: To compare the time taken to establish a clinical diagnosis of Frontotemporal dementia (FTD) relative to a diagnosis of early onset Alzheimer's dementia (AD). METHODS: The data came from 89 patients under the age of 65 years, 52 of whom met the Manchester-Lund criteria for Frontotemporal dementia; 20 of these came from Lund University Hospital in Sweden. The other 32 patients with FTD along with 37 subjects who fulfilled the ICD-10 criteria for early onset Alzheimer's disease were recruited from four memory clinics and two neurology departments in Norway. RESULTS: For FTD patients in Norway it took 59.2 months (SD 36.1) from the onset of illness until a clinical FTD diagnosis was made. The corresponding time period for FTD patients in Sweden is 49.5 months (SD 24.5) and for AD patients in Norway 39.1 months (SD 19.9). The time from the first visit to a medical doctor until a diagnosis was made for the FTD patients in Norway was 34.5 months (SD 22.6), for the Swedish FTD patients 23.1 months (SD 22.4) and for the AD patients 25.9 months (SD 13.1). In all, 71% of FTD patients and 30% of AD patients initially received a non-dementia diagnosis. CONCLUSION: More knowledge about early presenting cognitive and behavioural signs of FTD is needed in both primary and secondary health care to reduce the time period needed to establish a clinical diagnosis of FTD. Copyright (c) 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

AIMS: To study cardio-cerebrovascular disease and clinical features, such as falls, dizziness/unsteadiness, urinary incontinence, hallucinations/delusions and delirium in neuropathologically defined subgroups of vascular Dementia (VaD): pure Small Vessel Dementia (SVD), combined SVD and Alzheimer's disease (SVD-AD), pure Large Vessel Dementia (LVD) and pure Hypoxic Hypoperfusive Dementia (HHD), and to analyse the clinical differences between these groups. MATERIALS AND METHODS: From 175 consecutive cases with neuropathologically verified VaD cases with pure SVD (n = 36) and SVD-AD (n = 38) with varying severity of AD pathology were selected and studied with respect to cardio-cerebrovascular and other clinical features. Furthermore, a comparison between pure SVD, pure LVD (n = 7) and pure HHD (n = 6) was made. RESULTS: Neither cardiovascular symptoms, hypertension, Transitoric Ischemic Attacks (TIA) nor complete cerebrovascular lesions (CVL) differed significantly between the pure SVD and SVD-AD groups. However, a wide variation of clinical features were reported. The prevalence of cardiovascular features varied markedly in the pure groups, with the highest prevalence consistently found in the LVD group. Hypertension was common in the pure LVD and SVD-groups, while it was a rare finding in the HHD-group. TIA and/or CVL were, as expected, most common in the LVD-group. CONCLUSION: In conclusion, this longitudinal and retrospective study of VaD shows important clinical similarities as well as differences between pathologically defined subgroups. Hopefully these findings will contribute to a better understanding of etiopathogenetic and diagnostic issues and form a solid basis for possible treatment strategies in VaD. [ABSTRACT FROM AUTHOR]

Background: This study examines relations between regional cerebral blood flow (rCBF) and neuropsychological test results, age at onset and duration of disease in patients with frontotemporal-type dementia (FTD).Method: Sixteen patients with a diagnosis of probable FTD were examined using single photon emission computerised tomography (SPECT) with 99mTc-HMPAO as the tracer. The rCBF of 14 regions of interest relative to cerebellar blood flow was calculated. Psychological tests assessing language, verbal fluency, memory and visuospatial constructive ability were given.Results: Correlations were demonstrated between a global impairment score and relative blood flow in lateral frontal, medial frontal and left orbital frontal areas. Verbal fluency scores correlated with left lateral frontal, medial frontal and left anterior inferior temporal blood flow. No relationships between decrease in CBF and age at onset or duration of disease, or between impaired cognitive function and age at onset or duration of disease were found.Conclusions: The present study demonstrates a close coupling between reduced rCBF and specific neuropsychological deficits in FTD. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) constitutes a spectrum of neurodegenerative disorders associated with degeneration of, predominantly, the frontal and temporal lobes. The clinical heterogeneity is evident, and early diagnosis is a challenge. The primary objectives were to characterize psychotic symptoms, initial clinical diagnoses and family history in neuropathologically verified FTD-patients and to analyze possible correlations with different neuropathological findings., Methods: The medical records of 97 consecutive patients with a neuropathological diagnosis of frontotemporal lobar degeneration (FTLD) were reevaluated. Psychotic symptoms (hallucinations, delusions, paranoid ideas), initial diagnosis and family history for psychiatric disorders were analyzed., Results: Psychotic symptoms were present in 31 patients (32%). There were no significant differences in age at onset, disease duration or gender between patients with and without psychotic symptoms. Paranoid ideas were seen in 20.6%, and hallucinations and delusions in 17.5% in equal measure. Apart from a strong correlation between psychotic symptoms and predominantly right-sided brain degeneration, the majority of patients (77.4%) were tau-negative. Only 14.4% of the patients were initially diagnosed as FTD, while other types of dementia were seen in 34%, other psychiatric disorders in 42%, and 9.2% with other cognitive/neurological disorders. The patients who were initially diagnosed with a psychiatric disorder were significantly younger than the patients with other initial clinical diagnoses. A positive heredity for dementia or other psychiatric disorder was seen in 42% and 26% of the patients respectively., Conclusions: Psychotic symptoms, not covered by current diagnostic criteria, are common and may lead to clinical misdiagnosis in FTD.

Frontotemporal dementia (FTD) is associated with a broad spectrum of clinical characteristics. The objective of this study was to analyze the prevalence of unexplained somatic complaints in neuropathologically verified FTD. We also examined whether the somatic presentations correlated with protein pathology or regional brain pathology and if the patients with these somatic features showed more depressive traits. Ninety-seven consecutively neuropathologically verified FTLD patients were selected. All 97 patients were part of a longitudinal study of FTD and all medical records were systematically reviewed. The somatic complaints focused on were headache, musculoskeletal, gastro/urogenital and abnormal pain response. Symptoms of somatic character (either somatic complaints and/or abnormal pain response) were found in 40.2%. These patients did not differ from the total group with regard to gender, age at onset or duration. Six patients showed exaggerated reactions to sensory stimuli, whereas three patients showed reduced response to pain. Depressive traits were present in 38% and did not correlate with somatic complaints. Suicidal behavior was present in 17 patients, in 10 of these suicidal behavior was concurrent with somatic complaints. No clear correlation between somatic complaints and brain protein pathology, regional pathology or asymmetric hemispherical atrophy was found. Our results show that many FTD patients suffer from unexplained somatic complaints before and/or during dementia where no clear correlation can be found with protein pathology or regional degeneration. Somatic complaints are not covered by current diagnostic criteria for FTD, but need to be considered in diagnostics and care. The need for prospective studies with neuropathological follow up must be stressed as these phenomena remain unexplained, misinterpreted, bizarre and, in many cases, excruciating.

Background: In 2011 the C9ORF72 repeat expansion was identified as the most frequent genetic mutation underlying FTD and ALS. The main aim of this study was to investigate clinical characteristics in a large C9ORF72-positive FTD family, and to compare these with the neuropathological findings., Methods: The clinical records of 12 related FTD patients were thoroughly evaluated. The five neuropathologically examined cases were revised using additional TDP-43 immuno-stainings. Four cases were screened for the C9ORF72 expansion., Results: All 12 patients fulfilled the criteria for bvFTD. Restlessness and social neglect were often among the first reported symptoms. Psychotic symptoms were reported in 8 patients. Somatic complaints were seen in 7 cases. All the neuropathologically examined cases were TDP-43 positive., Conclusions: The phenotype of this C9ORF72 hexanucleotide expansion carrier family was bvFTD. The clinical symptom profile was strikingly homogenous. Psychotic symptoms and somatic complaints were observed in most of the cases.

Background: Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype., Methods: We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed., Result: NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017)., Conclusions: The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values.

The aim of this study was to analyze the medical history, with regards to previous remote depression, in patients with neuropathologically verified Alzheimer's disease (AD), vascular dementia (VaD) and mixed AD/VaD. The 201 patients included (115 AD, 44 VaD and 42 mixed AD/VaD) had been referred to the Psychogeriatric/Psychiatric Department, Lund University Hospital, for psychogeriatric investigation and were followed-up with clinical records and detailed information on psychiatric history prior to the onset of dementia. Depression was considered to exist when the patient had consulted a psychiatrist or physician and had been diagnosed with a "depressive episode" or "depression" and when anti-depressants and/or other specific treatments had been prescribed. Twenty patients (10%) had suffered from depression earlier in life well before the onset of dementia. Eight of the 9 AD patients with a previous diagnosis of depression had suffered from only one depressive episode and all had responded well to treatment, with complete recovery. In the VaD group, 8 out of 9 patients suffered two or more depressive episodes and only two recovered completely. Events with a possible significant relationship to depression were seen in 8 of the 9 AD patients but in only 1 of the 9 VaD patients. Psychotic symptoms were more common in VaD than in the AD group. The treatment modality of depression was similar in the groups. In conclusion, a history of depression prior to dementia is more common and more therapy-resistant in VaD than in AD., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Frontotemporal dementia (FTD) as an important clinical entity was rediscovered in Lund and Manchester in the early 1990s. Here we show that the large Lund pedigree with behavioral variant of frontotemporal dementia previously described with this disorder has an expansion in the recently described C9ORF72 locus on chromosome 9., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Previous publications have shown a high diagnostic sensitivity and specificity of three short clinical rating scales for Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VaD) validated against neuropathological (NP) diagnoses. In this study, the aim was to perform an exploratory factor analysis of the items in these clinical rating scales. The study included 190 patients with postmortem diagnoses of AD (n = 74), VaD (n = 33), mixed AD/VaD (n = 31), or FTD (n = 52). The factor analysis produced three strong factors. Factor 1 contained items describing cerebrovascular disease, similar to the Hachinski Ischemic Score. Factor 2 enclosed major clinical characteristics of FTD, and factor 3 showed a striking similarity to the AD scale. A fourth symptom cluster was described by perception and expression of emotions. The factor analyses strongly support the construct validity of the diagnostic rating scales.

The aims were to evaluate the cognitive performance and clinical diagnosis in patients (<75 years) seeking help for subjective memory complaints, to determine the prevalence of certain psychiatric symptoms and to conduct follow-up examinations. At baseline 41% showed normal cognitive performance (subjective memory impairment; SMI), 37% fulfilled criteria for mild cognitive impairment (MCI) and 22% were classified as dementia. There were significant associations between the three groups and experiences of psychosocial stress and feelings of anxiety. The proportion of psychosocial stress was significantly higher in SMI vs. MCI and SMI vs. dementia. Feelings of anxiety were significantly higher in SMI vs. MCI. At the 3-year follow-up, 88% of the SMI patients remained stable SMI and 60% of the MCI patients remained stable. There was a significant reduction of psychosocial stress and moderate reduction of feelings of anxiety among the SMI patients. The findings indicate that the risk of patients with SMI developing dementia is small within a 3-year span. We propose that subjective memory complaints might be influenced by the presence of psychosocial stress and feelings of anxiety disturbing the memory processes and interfering with the patients' evaluation of their memory function., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD., Design: A prospective longitudinal clinical work-up with postmortem NP examination., Participants: Two hundred nine patients with dementia referred for clinical evaluation and follow-up., Methods: The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses., Results: The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales., Conclusions: All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings.

The objectives of this study were to examine potential clinical and neuropsychological changes over time in non-demented patients with subjective memory complaints (

Background: Clinical dementia diagnoses are not always consistent with neuropathological findings. As correct diagnosis is important for treatment and care, new diagnostic possibilities for dementia are in demand. Cerebrospinal fluid biomarkers should ideally be able to identify ongoing processes in the brain, but need to be further compared with neuropathological findings for evaluation of their diagnostic validity., Methods: This study included 43 patients with a clinical dementia disorder. All patients were neuropathologically examined at the University Hospital in Lund, Sweden, during the years 2001-2008, and all had a lumbar puncture carried out as part of the clinical investigation during the time of cognitive impairment., Results: Of eight patients, five with Alzheimer's disease had elevated total tau protein (T-tau) and decreased amyloid beta 1-42 protein (Abeta42), while both values for the other three patients were normal. Slightly elevated T-tau and/or decreased Abeta42 were also seen in several patients with other dementia diagnoses such as Lewy body disease, frontotemporal lobar degeneration and vascular dementia. Furthermore, T-tau levels did not differ markedly between patients with morphologically tau-positive and tau-negative frontotemporal lobar degeneration. Also, seven of nine patients with Creutzfeldt-Jacob disease exhibited pronounced elevation in T-tau concentration., Conclusion: From this rather limited study, being the first of its kind in Sweden, we may conclude that there is no perfect concordance between cerebrospinal fluid biomarker levels and pathological findings, which should be taken into account in the clinical diagnostic setting., (2010 The Alzheimer's Association. All rights reserved.)