Search

Retention of 18F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if 18F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. All underwent 18F-Flortaucipir PET and MRI scanning. Data from 39 Alzheimer's Disease patients were used for comparison. PET tracer retention was assessed both at the region-of-interest (ROI) and at the voxel-level. Further, autoradiography using 3H-Flortaucipir was performed. SvPPA patients exhibited higher 18F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18F-Flortaucipir binding was slightly increased in the inferior frontal lobes in the ROI based analysis, but these results were not replicated in the voxel-based analysis. Autoradiography did not show specific binding in svPPA cases or in C9orf72-mutation carriers. In conclusion, temporal lobe 18F-Flortaucipir retention was observed in some cases of svPPA, but the uptake was of a lower magnitude compared to AD dementia. C9orf72-mutation carriers exhibited none or limited 18F-Flortaucipir retention, indicating that 18F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon. [ABSTRACT FROM AUTHOR]

Aim: To assess the merit of clinical assessment tools in a neurocognitive screening following out-of-hospital cardiac arrest (OHCA)., Methods: The neurocognitive screening that was evaluated included the performance-based Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT), the patient-reported Two Simple Questions (TSQ) and the observer-reported Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest (IQCODE-CA). These instruments were administered at 6-months in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. We used a comprehensive neuropsychological test battery from a TTM2 trial sub-study as a gold standard to evaluate the sensitivity and specificity of the neurocognitive screening., Results: In our cohort of 108 OHCA survivors (median age = 62, 88% male), the most favourable cut-off scores were: MoCA < 26; SDMT z ≤ -1; IQCODE-CA ≥ 3.04. The MoCA (sensitivity 0.64, specificity 0.85) and SDMT (sensitivity 0.59, specificity 0.83) had a higher classification accuracy than the TSQ (sensitivity 0.28, specificity 0.74) and IQCODE-CA (sensitivity 0.42, specificity 0.60). When using the cut-points for MoCA or SDMT in combination to identify neurocognitive impairment, sensitivity improved (0.81, specificity 0.74), area under the curve = 0.77, 95% CI [0.69, 0.85]. The most common unidentified impairments were within the episodic memory and executive functions domains, with fewer false negative cases on the MoCA or SDMT combined., Conclusion: The MoCA and SDMT have acceptable diagnostic accuracy for screening for neurocognitive impairment in an OHCA population, and when used in combination the sensitivity improves. Patient and observer-reports correspond poorly with neurocognitive performance., Clinicaltrials: gov Identifier: NCT03543371., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA., Methods: This was a prospective case-control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes., Results: Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ - 1 (at least borderline-mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ - 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = - 0.37, 95% confidence intervals [- 0.61, - 0.12]), verbal (MD = - 0.34 [- 0.62, - 0.07]), and visual/constructive functions (MD = - 0.26 [- 0.47, - 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = - 0.44 [- 0.82, - 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance., Conclusions: In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue., Trial Registration: ClinicalTrials.gov, NCT03543371. Registered 1 June 2018., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The cerebellum plays a major role in balance, motor control and sensorimotor integration, but also in cognition, language, and emotional regulation. Several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as neurological diseases such as spinocerebellar ataxia type 3 (SCA3) are associated with differences in cerebellar function. Morphological abnormalities in different cerebellar subregions produce distinct behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. The specific contribution of the cerebellum to typical development may therefore involve the optimization of the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains. Here, we review cerebellar structural and functional differences between healthy and patients with ADHD, ASD, and SCA3, and explore how disruption of cerebellar networks affects the neurocognitive functions in these conditions. We discuss how cerebellar computations contribute to performance on cognitive and motor tasks and how cerebellar signals are interfaced with signals from other brain regions during normal and dysfunctional behavior. We conclude that the cerebellum plays a role in many cognitive functions. Still, more clinical studies with the support of neuroimaging are needed to clarify the cerebellum's role in normal and dysfunctional behavior and cognitive functioning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cundari, Vestberg, Gustafsson, Gorcenco and Rasmussen.)

Objective: To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods., Methods: An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest., Results: Among the long-term surviving participants ( N = 457), serum NFL ( n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1-2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]-TSQ) to strong (CPC-MMSE)., Conclusions: The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.

Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo, especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process., Competing Interests: HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is also a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS). These do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA., Methods: This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses., Discussion: In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA., Trial Registration: ClinicalTrials.gov, NCT03543371 . Registered 1 June 2018.

Background: Differentiating mild cognitive impairment (MCI) from subjective cognitive decline (SCD) is important because of the higher progression rate to dementia for MCI and when considering future disease-modifying drugs that will have treatment indications at the MCI stage., Objective: We examined if the two most widely-used cognitive tests, the Mini-Mental State Examination (MMSE) and clock-drawing test (CDT), and a test of attention/executive function (AQT) accurately can differentiate MCI from SCD., Methods: We included 466 consecutively recruited non-demented patients with cognitive complaints from the BioFINDER study who had been referred to memory clinics, predominantly from primary care. They were classified as MCI (n = 258) or SCD (n = 208) after thorough neuropsychological assessments. The accuracy of MMSE, CDT, and AQT for identifying MCI was examined both in training and validation samples and in the whole population., Results: As a single test, MMSE had the highest accuracy (sensitivity 73%, specificity 60%). The best combination of two tests was MMSE < 27 points or AQT > 91 seconds (sensitivity 56%, specificity 78%), but in logistic regression models, their AUC (0.76) was not significantly better than MMSE alone (AUC 0.75). CDT and AQT performed significantly worse (AUC 0.71; p < 0.001-0.05); otherwise no differences were seen between any combination of two or three tests., Conclusion: Neither single nor combinations of tests could differentiate MCI from SCD with adequately high accuracy. There is a great need to further develop, validate, and implement accurate screening-tests for primary care to improve accurate identification of MCI among individuals that seek medical care due to cognitive symptoms.

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD., Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset)., Results: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test ( r s =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri ( r s =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival., Conclusion: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities., Competing Interests: Competing interests: The authors report no conflicts of interest relevant to this study. LHHM is supported by Alzheimer Nederland (grant number WE.09 2014 04). ALB and JCR are supported by the NIH (U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983) and the Association for Frontotemporal Degeneration. ALB, JCR and LDK are supported by the Bluefield Project to Cure Frontotemporal Dementia. The Dementia Research Centre is supported by Alzheimer’s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility as well as an Alzheimer’s Society grant (AS-PG-16-007). JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). IOCW is supported by an MRC Clinical Research Training Fellowship (MR/M018288/1). AS is supported by the Swedish Society for Medical Research. CET is supported by ZonMW Memorabel Program (grant number 733050206). JCvS is supported by the Dioraphte Foundation., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The aim of this study was to assess the psychometric properties of a Swedish version of the Hayling test (HT-S) and its clinical utility in a group of patients with different frontotemporal dementia (FTD) syndromes. Early diagnosis of FTD is a challenge and requires a broad arsenal of assessment methods, neuropsychological tests not the least. The Hayling test assesses executive functions including initiation, efficiency and response inhibition., Methods: Seventy-six healthy controls were included as well as patients with the behavioral variant FTD (bvFTD; n = 17), semantic dementia (SD, n = 6), and progressive supranuclear palsy (n = 12). The Color Word Interference Test was administered to examine the construct validity., Results: Age showed a correlation with better performances in younger participants whereas the importance of sex and education were less evident. The split half reliability and internal consistency were equal to, or better, than reported for the original version. The interrater reliability was excellent. The construct validity was supported, nevertheless indicating partly different processes behind the performances of the two tests. The FTD group performed significantly worse than healthy controls on efficiency and response inhibition and there were also significant differences in performances between the syndromes despite small samples., Conclusions: The psychometric properties and clinical utility of the Swedish version are satisfactory for measuring efficiency and response inhibition with results indicating dissimilar profiles in the performances in the different syndromes. These results need to be corroborated in larger samples. (JINS, 2019, 25, 195-203).

Changes over time in information processing speed and executive functions (EFs) were studied in patients with suspected low-grade gliomas (LGG) 3 years after diagnosis. Using a person-oriented approach, the study aimed at focusing solely on two cognitive domains known to be significant in the understanding of the impact of white matter diseases. The Barkley's hybrid model of EFs was used as a theoretical framework for the evaluation of EFs. The majority of the patients showed a decline in at least one of these two cognitive domains indicating that the progress of diffuse brain injury cannot be neglected in understanding neuropsychological changes over time in patients with LGG. In our sample, higher age and radiological signs of radiotherapy-induced brain atrophy were seen in patients with a decline in both domains.

Aim: To examine the psychometric properties of a modified version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), for a cardiac arrest population (IQCODE-CA)., Methods: The IQCODE-CA, a 26-item observer-reported questionnaire, was completed by informants, defined as relatives or close friends, of 268 out-of-hospital cardiac arrest (OHCA) survivors who participated in the Target Temperature Management trial in a scheduled follow-up 180±14days after OHCA. Survivors completed the Mini Mental State Examination (MMSE), the Rivermead Behavioural Memory Test (RBMT) and the Hospital Anxiety and Depression Scale (HADS). An exploratory factor analysis was performed. Associations between IQCODE-CA results and demographic variables along with other instruments were calculated. Area under the curve (AUC) ratios were evaluated to examine discrimination., Results: The IQCODE-CA measured one factor, global cognitive decline, with high internal consistency (ordinal α=0.95). Age, gender or education did not influence the IQCODE-CA score. Associations with performance-based measures of global cognitive function as well as anxiety and depression ranged from small to moderate (r s =-0.29 to 0.38). AUC ratios ranged from fair to good (0.72-0.81). According to the MMSE and RBMT, the optimal cut-off score to identify cognitive decline on the IQCODE-CA was 3.04. Using this value, 53% of the survivors were under the cut-off., Conclusions: The IQCODE-CA identified a large amount of survivors with possible cognitive problems, making it useful when screening for cognitive decline post-CA. Due to lower AUC ratios than desired, additional performance-based measures should be used to improve the overall screening methodology., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the "prefrontal" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition., Materials and Methods: Magnetic resonance imaging scans from 28 patients with bvFTD and 26 healthy controls were manually traced using image analysis software (ITK-SNAP). The resulting 3-D objects underwent volumetric analysis and shape analysis, through spherical harmonic description with point distribution models (SPHARM-PDM). Correlations with size and shape were sought with clinical measures in the bvTFD group, including Frontal Behavioural Inventory, Clinical Dementia Rating for bvFTD, Color Word Interference, Hayling part B and Brixton tests, and Trail-Making Test., Results: Caudate nuclei and putamina were significantly smaller in the bvFTD group compared to controls (left caudate 16% smaller, partial eta squared 0.173, p=0.003; right caudate 11% smaller, partial eta squared 0.103, p=0.023; left putamen 18% smaller, partial eta squared 0.179, p=0.002; right putamen 12% smaller, partial eta squared 0.081, p=0.045), with global shape deflation in the caudate bilaterally but no localised shape change in putamen. In the bvFTD group, shape deflations on the left, corresponding to afferent connections from dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity. Global shape deflation in the putamen correlated with Frontal Behavioural Inventory scores-higher scoring on negative symptoms was associated with the left putamen, while positive symptoms were associated with the right. Other cognitive tests had poor completion rates., Conclusion: Behavioural symptoms and severity of bvFTD are correlated with abnormalities in striatal size and shape. This adds to the promise of imaging the striatum as a biomarker in this disease.

Importance: Before adding cerebrospinal fluid (CSF) biomarkers to the diagnostic workup of Alzheimer disease, it needs to be determined whether CSF biomarkers analyzed in routine clinical practice can reliably predict cortical β-amyloid (Aβ) deposition., Objectives: To study whether CSF biomarkers, analyzed consecutively in routine clinical practice during 2 years, can predict cortical Aβ deposition and to establish a threshold for Aβ42 abnormality., Design, Setting, and Participants: This cross-sectional study (The Swedish BioFINDER [Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably] Study) was conducted at 3 memory clinics. It involved consecutively referred, nondemented patients with mild cognitive symptoms (original cohort, n = 118; validation cohort, n = 38)., Exposures: Amyloid positron emission tomography imaging with 18F-flutemetamol., Main Outcomes and Measures: Analyses of CSF Aβ42, total tau, and phosphorylated tau using an enzyme-linked immunosorbent assay (INNOTEST) in clinical samples., Results: The agreement between Aβ classification with CSF Aβ42 and 18F-flutemetamol positron emission tomography was very high (κ = 0.85). Of all the cases, 92% were classified identically using an Aβ42 cutoff of 647 pg/mL or less. Cerebrospinal fluid Aβ42 predicted abnormal cortical Aβ deposition accurately (odds ratio, 165; 95% CI, 39-693; area under the receiver operating characteristic curve, 0.94; 95% CI, 0.88-0.97). The association was independent of age, sex, APOE (apolipoprotein E) genotype, hippocampal volume, memory, and global cognition (adjusted odds ratio, 169; 95% CI, 25-1143). Using ratios of CSF Aβ42:tau or Aβ42:phosphorylated tau did not improve the prediction of Aβ deposition. Cerebrospinal fluid Aβ42 correlated significantly with Aβ deposition in all cortical regions. The highest correlations were in regions with high 18F-flutemetamol retention (eg, posterior cingulum and precuneus, r = -0.72). 18F-flutemetamol retention, but not CSF Aβ42, correlated significantly with global cognition (r = -0.32), memory function (r = -0.28), and hippocampal volume (r = -0.36) among those with abnormal Aβ deposition. Finally, the CSF Aβ42 cutoff derived from the original cohort (≤647 pg/mL) had an equally high agreement (95%; κ = 0.89) with 18F-flutemetamol positron emission tomography in the validation cohort., Conclusions and Relevance: Cerebrospinal fluid Aβ42 analyzed consecutively in routine clinical practice at an accredited laboratory can be used with high accuracy to determine whether a patient has normal or increased cortical Aβ deposition and so can be valuable for the early diagnosis of Alzheimer disease. Abnormal 18F-flutemetamol retention levels correlate with disease stage in patients with mild cognitive symptoms, but this is not the case for CSF Aβ42 measurements.

Objectives: Frontotemporal dementia (FTD) is considered to be a mainly early-onset neurodegenerative disorder with a strong hereditary component. The aim of the study was to investigate age-related incidence and family history in FTD compared to other dementia disorders, especially Alzheimer's disease (AD)., Methods: The Swedish Dementia Registry (SveDem) registers all new cases of dementia diagnosed by the participating centres, including data on demographics, diagnosis, and investigations used. Data for the period 2008-2011 were extracted and compared with age-related population data on a regional and national level., Results: There were 20 305 patients registered in SveDem during 2008-2011, whereof 352 received a diagnosis of FTD. Mean age at diagnosis for FTD was 69.6 years and almost 70% of FTD cases were 65 years or older at the time of diagnosis. Both FTD and AD showed an increased incidence with age, which reached a maximum in the age group 80-84 years at 6.04 and 202 cases per 100 000 person-years, respectively. The proportion of cases with a positive family history was significantly lower in FTD than in AD., Conclusions: Contrary to general opinion within the field, data from SveDem show that the incidence of FTD increases with age, and that the majority of cases are diagnosed after the age of 65 years. In addition, data from SveDem might suggest that the importance of hereditary factors in general is similar in FTD and AD. The recognition of these findings has important consequences for the diagnosis, treatment and care of patients with FTD.

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.)

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

The aims are to study personality characteristics of patients with memory complaints and to assess the presence of objective (OMI) versus subjective (SMI) memory impairment, the affective status, as well as potential gender differences. The patients were assessed by means of a neuropsychiatric examination and a neuropsychological test-battery. The Swedish version of the revised NEO Personality Inventory (NEO PI-R) and the Hospital Anxiety and Depression Scale (HADS) were used. The 57 patients (38 women, 19 men, mean age 56.9) differed from the Swedish normative group in three of the five personality factors: neuroticism, extraversion and agreeableness. This was mainly because of the scores of the female patients. Approximately half of the patients had OMI. No differences regarding personality factors or affective status were found between OMI and SMI patients. The female patients scored significantly higher than the male patients on symptoms of anxiety and depression. Neuroticism and symptoms of depression interacted with memory performance and gender. Our findings demonstrate the importance of applying an objective assessment of memory functions and a gender perspective when studying patients with memory complaints.