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Atrial fibrillation (AF) is associated with cognitive decline and dementia irrespective of AF-related ischemic stroke. We investigated whether AF burden after ablation in patients with symptomatic paroxysmal AF has an impact on cognitive function. After enrolment to the prospective MACPAF study, study patients received an insertable loop recorder (ILR) and underwent serial neurological/cognitive assessment. To compare cognitive function, the delta of baseline and six months test results (Δpre/post) and a score to assess overall cognitive performance were computed. Thirty patients (median age 65 years (IQR 57-69), 40% female) were divided into groups according to median AF burden (

Background/Objective: Apolipoprotein E (ApoE) has an active part in the pathogenesis of Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations have been reported in AD patients. In search of a biomarker potentially predictive of cognitive, functional, or motor decline, we analyzed the CSF to serum ratios of ApoE levels (CSF/serum ApoE) in AD patients in this regard. Methods: Subjects with newly diagnosed AD were followed within a longitudinal observational study (rpAD study). Annual neuropsychological testing and physical examination were performed. Multiple regression analyses were used to determine possible associations of the ApoE CSF/serum concentration ratios and velocity of decline on a variety of cognitive, functional and motor scales (MMSE, iADL, bADL, GDS, UPDRSIII) adjusted for relevant co-variables. Results: CSF/serum ratios of ApoE levels were associated with progression on the UPDRSIII (change of UPDRSIII slope [pt/yr] per unit of ApoE CSF/serum = –0.06, p < 0.01) and instrumental ADL scale (change of iADL slope [pt/yr] per unit of ApoE CSF/serum = 0.01, p = 0.01) (“the lower the ratio, the faster the deterioration” and vice versa). Secondarily, higher age at onset was associated with faster UPDRSIII progression, antidepressant use with faster iADL decline, and better baseline function with more rapid decline on either MMSE, iADL, or GDS scale. Conclusion: Here, CSF/serum ApoE at time of AD diagnosis was shown to be inversely associated with medium-term functional and motor progression. Whether this ratio qualifies for the use as a predictive biomarker must be validated in larger cohort studies over the long term.

Objective: Cerebral small vessel disease is the most common cause of vascular cognitive impairment and typically manifests with slowed processing speed. We investigated the impact of lesion location on processing speed in age-related small vessel disease. Methods: A total of 584 community-dwelling elderly underwent brain MRI followed by segmentation of white matter hyperintensities. Processing speed was determined by the timed measure of the Trail Making Test part B. The impact of the location of white matter hyperintensities was assessed by voxel-based lesion-symptom mapping and graph-based statistical models on regional lesion volumes in major white matter tracts. Results: Voxel-based lesion-symptom mapping identified multiple voxel clusters where the presence of white matter hyperintensities was associated with slower performance on the Trail Making Test part B. Clusters were located bilaterally in the forceps minor and anterior thalamic radiation. Region of interest–based Bayesian network analyses on lesion volumes within major white matter tracts depicted the same tracts as direct predictors for an impaired Trail Making Test part B performance. Conclusions: Our findings highlight damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in age-related small vessel disease.

A proportion of idiopathic Parkinson's disease patients (PDidiopathic ) with dementia show altered CSF profiles of amyloid β (Aβ) and Tau. PD patients with Glucocerebrosidase (GBA) mutations (PDGBA ) present with even more cognitive decline than seen in PDidiopathic .The objective of this study was to evaluate whether CSF profiles of Aβ and tau are associated with the prominent cognitive impairment in PDGBA .CSF levels of Aβ1-42 , t-Tau, p-Tau, and total alpha-synuclein were assessed in 479 participants (50 PDGBA , 308 PDidiopathic , 121 healthy controls).Older age was associated with cognitive impairment in PDGBA and PDidiopathic . Despite prominent cognitive impairment, PDGBA showed similar CSF levels of Aβ1-42 , t-Tau, and p-Tau as seen in healthy controls. In contrast, lower levels of Aβ1-42 and higher levels of t-Tau and p-Tau were associated with worse cognitive performance in PDidiopathic .The prominent cognitive impairment in PDGBA seems not primarily associated with Aβ and Tau profiles in CSF. © 2017 International Parkinson and Movement Disorder Society.

Background Mild parkinsonian signs (MPS) are common in older people and are associated with an increased risk of different neurodegenerative diseases. This study prospectively evaluates the longitudinal course of cognitive performance in older individuals with MPS. Methods From the TREND study, 480 individuals neurologically healthy at baseline, aged between 50 and 80 years, with complete follow-up data for three assessments within a mean of 43.8 months, were included in this analysis. Participants underwent a detailed cognitive test battery, evaluation of prodromal markers for neurodegenerative diseases and history of vascular diseases at each study visit. In addition, plasma levels of amyloid-beta (Aβ)1–40 and Aβ1–42 were evaluated longitudinally. Results In 52 (11 %) of the 480 participants, MPS could be detected at baseline. These individuals had cognitive deficits significantly more often compared with controls at each time point and their cognitive performance showed a steeper decline during follow-up. In addition, their levels of plasma Aβ1–42 were significantly lower than those of controls, and declined more rapidly over time. Conclusions This longitudinal study shows that MPS are associated with cognitive decline and decrease in plasma Aβ1–42, possibly indicating an ongoing neurodegenerative process. Electronic supplementary material The online version of this article (doi:10.1186/s13195-016-0209-7) contains supplementary material, which is available to authorized users.

Objectives: To examine the effect of cardiovascular and metabolic diseases on initial cognitive test performance and rate of change in three cognitive measures. Design: Prospective cohort study. Setting: General practices in six towns throughout Germany. Participants: Three thousand three hundred twenty-seven participants aged 75 and older (average 79.7 ± 3.6). Measurements: Data were collected during home visits every 18 months and included sociodemographic variables, depression, disease status, drug intake, and cognition. Results: Although the presence of transient ischemic attack (TIA) or stroke and diabetes mellitus was related to poor initial cognitive test performance, the presence of those and other far-reaching chronic diseases or a higher disease burden were not related to the rate of change in cognition over time. Conclusion: Diabetes mellitus, stroke and TIA affect cognitive test performance beyond well-known sociodemographic variables and depressive symptoms, although none of these diseases contributed to cognitive decline over time. In practical terms, prevention and diagnosis of cardiovascular and metabolic diseases may be essential to cognitively healthy aging.

The study aims to report service use and costs for patients with Alzheimer's disease (AD) and to explore the incremental influence of sociodemographic and illness-related determinants in ambulatory and inpatient settings within the German health care system. 395 patients with dementia were recruited at the following sites: 1) University hospital, 2) general practitioners' offices, 3) office-based neurologists, 4) a regional psychiatric hospital, and 5) nursing homes. Sociodemographic, economic, and clinical parameters were assessed using a standardized questionnaire. Informal care was not evaluated. Disease severity was measured using the Mini-Mental Status Examination and the Alzheimer's Disease Assessment Scale - Cognitive Subscale. Neuropsychiatric status was assessed using the Geriatric Depression Scale, the Neuropsychiatric Inventory, and the Alzheimer's Disease Cooperative-Study-Activities of Daily Living. Annual total costs were estimated to be €13,080 per patient. The most important cost component was (long-term) care, constituting about 43% of total costs. Indirect costs comprised about 18% of total costs and were mainly due to reductions in working time of caregivers. Poorer functional status was associated with higher total and caregiving costs. In multivariate analyses, we identified younger age, female gender, and impaired activities of daily living as independent predictors of higher costs. Given that care for patients with AD is complex and expensive, our models were only able to explain about 17-43% of the variability in total costs. This suggests that further social and individual factors considerably influence the costs associated with AD. Direct medical care costs and long-term care costs related differently to the patient's clinical characteristics. Longitudinal and population-based studies are necessary for thoroughly evaluating the burden of disease.

Objective: To evaluate whether there exists distinct characteristics in glucocerebrosidase ( GBA )–associated Parkinson disease (PD) with regard to motor and nonmotor symptoms as well as imaging characteristics assessed by transcranial sonography (TCS). Methods: Twenty patients with PD with heterozygous GBA mutations (N370S, L444P) (GBA-PD) in comparison to 20 patients with sporadic PD negative for GBA mutations (sPD) were included. We assessed motor impairment with the Unified Parkinson’s Disease Rating Scale–III. Nonmotor symptoms were evaluated using the Montreal Cognitive Assessment, Neuropsychiatric Inventory, revised form of the Beck Depression Inventory, Parkinson Disease Sleep Scale, Sniffin’ Sticks, and Unified Multiple System Atrophy Rating Scale items 9–12. TCS imaging was used to detect morphologic characteristics. Results: Patients with GBA-PD more often had a variety of nonmotor symptoms, namely dementia, neuropsychiatric disturbances, and autonomic dysfunction, and had more severe cases, than patients with sPD. They also demonstrated a higher prevalence of a reduced echogenicity of the brainstem raphe assessed by TCS. Conclusions: Especially nonmotor symptoms seem to be very common in GBA-PD. Further studies are needed to validate these observations in order to better understand the pathogenesis of GBA-PD and develop specific therapeutic concepts.

This editorial refers to ‘High-sensitivity cardiac troponin T and cognitive function and dementia risk: the atherosclerosis risk in communities study’, by A.L.C. Schneider et al . on page doi:10.1093/eurheartj/ehu124. The term ‘cardiogenic dementia’ was first introduced in the Lancet some 25 years ago and was used to describe reduced cognitive function in the presence of cardiac failure.1 Schneider and colleagues now present novel data on the association of cardiac troponin T (cTnT) and cognitive function. High-sensitivity cTnT (hs-cTnT) assays were used to detect even minor elevations indicating subclinical myocardial damage.2 The authors evaluated serum samples available from 9472 individuals (mean age 63 years) of the ‘Atherosclerosis Risk in Communities (ARIC)’ population cohort without coronary heart disease, myocardial infarction, heart failure, or stroke at baseline. Strikingly, as many as two-thirds of all participants had hs-cTNT levels above the lower limit of detection (≥3 ng/L) while only 7% reached the higher pre-defined concentration (≥14 ng/L). The study combines two separate designs (i.e. cross-sectional and prospective) with the following two major findings: (i) elevations in hs-cTnT were associated with lower scores in memory and executive function tests independent of traditional risk factors; (ii) elevated hs-cTNT was also predictive for incident hospitalization with an ICD-9 (International Classificiation of Diseases 9th revision) code for dementia during a median of 13 years of follow-up. These findings were robust through several elaborate sensitivity analyses and adjustments for several potential confounders.2 The authors have to be commended for their work. They present data on a large patient sample, used specific and highly sensitive assays, state-of-the-art statistical evaluation, and comprehensive measurement …

Importance: Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood. Objective: To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis. Design, Setting, and Participants: A cross-sectional study was conducted at the Departments of Neurology at Charite-Universitaetsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015. Main Outcomes and Measures: Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy). Results: Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P

Alzheimer's disease (AD) is the most common cause of cognitive decline in the elderly and is characterized by massive neuronal loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. Decreased SCF plasma levels have been described in AD patients. Whether SCF plasma levels are also associated with the rate of cognitive decline in AD patients has not been reported so far. In the present study, we demonstrate that SCF plasma levels are significantly decreased in AD patients with fast cognitive decline (decrease of Mini-Mental State Examination (MMSE) score > 4 after one year; n = 12) compared to AD patients with slow cognitive decline (decrease of MMSE score ≤ 4 after one year; n = 28) (fast versus slow cognitive decline: mean ± SD: 1051.1 ± 178.7 versus 1237.9 ± 274.2 pg/ml; p = 0.037). Moreover, SCF plasma levels correlated with the rate of cognitive decline after one year follow-up period (r = 0.315; p = 0.048). In a multiple linear regression analysis, independent predictors of the rate of cognitive decline in our study cohort were age, MMSE scores at baseline, SCF plasma levels, as well as brain-derived neurotrophic factor and activated glycoprotein (GP) IIb/IIIa. These results suggest that lower SCF plasma levels are associated with a higher rate of cognitive decline in AD patients. Thus, treatment strategies increasing SCF plasma levels could be useful for delaying the progression of AD. Further prospective studies are needed to elucidate the value of plasma SCF in a multimarker approach determining AD prognosis.

Recent studies have provided evidence that uric acid (UA), a natural antioxidant, may play a role in the development and progression of Parkinson's disease (PD) and of dementia. In this clinical study we were therefore interested in the role of UA in Lewy body disorders (LBD), which includes Parkinson's disease (PD) and a common form of neurodegenerative dementias, dementia with Lewy bodies (DLB). Ninety-five LBD patients (55 non-demented PD patients, PDND; 20 PD patients with dementia, PDD; and 20 DLB patients) and 76 controls underwent clinical and biochemical analyses including, from a subcohort, cerebrospinal fluid (CSF) analyses, and analysis of three single nucleotide polymorphisms (SNPs) known to be associated with altered serum UA levels. We confirmed previous findings of lowered serum UA levels in LBD patients compared to controls. In CSF, UA levels were significantly higher in PDND patients (median 0.7 mg/dl) compared only to demented LBD patients (0.4 mg/dl; p = 0.03), but not to controls (0.5 mg/dl; p = 0.12). CSF UA levels correlated positively with CSF Aβ42 levels. This correlation was highest in controls (ρ = 0.67), intermediate in PDND (ρ = 0.49), but not observable in demented LBD patients (ρ = 0.10). These findings suggest an involvement of serum UA in LBD occurrence, and an involvement of CSF UA in cognitive decline in LBD, possibly through the Aβ pathway. SNP rs1165205 (SLC17A3) was weakly associated with altered CSF UA levels. Taken together, our results provide first evidence for disease-relevant but potentially distinct roles of UA in the blood and CSF compartment, respectively, in LBD.

Introduction Mutations of Tau are associated with several neurodegenerative disorders. Recently, the Tau mutation A152T was described as a novel risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease. In vitro Tau-A152T shows a decreased binding to microtubules and a reduced tendency to form abnormal fibers. Results To study the effects of this mutation we generated a mouse model expressing human full-length Tau with this mutation (hTau40AT). At young age (2–3 months) immunohistological analysis reveals pathological Tau conformation and Tau-hyperphosphorylation combined with Tau missorting into the somatodendritic compartment of neurons. With increasing age there is Tau aggregation including co-aggregates of endogenous mouse Tau and exogenous human Tau, accompanied by loss of synapses (especially presynaptic failure) and neurons. From ~10 months onwards the mice show a prominent neuroinflammatory response as judged by activation of microglia and astrocytes. This progressive neuroinflammation becomes visible by in vivo bioluminescence imaging after crossbreeding of hTau40AT mice and Gfap-luciferase reporter mice. In contrast to other Tau-transgenic models and Alzheimer disease patients with reduced protein clearance, hTau40AT mice show a strong induction of autophagy. Although Tau-hyperphosphorylation and aggregation is also present in spinal cord and motor cortex (due to the Thy1.2 promoter), neuromotor performance is not affected. Deficits in spatial reference memory are manifest at ~16 months and are accompanied by neuronal death. Conclusions The hTau40AT mice mimic pathological hallmarks of tauopathies including a cognitive phenotype combined with pronounced neuroinflammation visible by bioluminescence. Thus the mice are suitable for mechanistic studies of Tau induced toxicity and in vivo validation of neuroprotective compounds. Electronic supplementary material The online version of this article (doi:10.1186/s40478-016-0281-z) contains supplementary material, which is available to authorized users.