We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG) for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations P CC 0 ij and their z-transforms z 0 ij between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z 0 ij successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sjögren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results..

Background Patients with Alzheimer’s disease (AD) are more prone to seizures and myoclonus, but relative risk of these symptoms among other dementia types is unknown. Objective To determine incidence of seizures and myoclonus in the three most common neurodegenerative dementias: AD, dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Methods Our institution’s medical records were reviewed for new-onset unprovoked seizures and myoclonus in patients meeting criteria for AD (n=1,320), DLB (n=178), and FTD (n=348). Cumulative probabilities of developing seizures and myoclonus were compared between diagnostic groups, whereas age-stratified incidence rates were determined relative to control populations. Results The cumulative probability of developing seizures after disease onset was 11.5% overall, highest in AD (13.4%) and DLB (14.7%) and lowest in FTD (3.0%). The cumulative probability of developing myoclonus was 42.1% overall, highest in DLB (58.1%). The seizure incidence rates, relative to control populations, were nearly 10 fold in AD and DLB, and 6 fold in FTD. Relative seizure rates increased with earlier age-at-onset in AD (age <50, 127 fold; 50–69, 21 fold; 70+, 2 fold) and FTD (age <50, 53 fold; 50–69, 9 fold), and relative myoclonus rates increased with earlier age-at-onset in all groups. Seizures began an average of 3.9 years after the onset of cognitive or motor decline, and myoclonus began 5.4 years after onset. Conclusions Seizures and myoclonus occur with greater incidence in patients with AD, DLB, and FTD than in the general population, but rates vary with diagnosis, suggesting varied pathomechanisms of network hyperexcitability. Patients often experience these symptoms early in disease, suggesting hyperexcitability could be an important target for interventions.

).Frontotemporal lobar degeneration (FTLD) is defined as a pathologic endophenotype characterized by atrophy of the frontal and temporal lobes leading to three clinical syndromes with partially overlapping microscopic pathology. These are jointly called frontotemporal dementia (FTD) and include the behavioral variant frontotemporal dementia (bvFTD) and two types of the primary progressive aphasias (PPA), 1 the nonfluent-agrammatic (nfvPPA) and the semantic (svPPA). The three syndromes are associated with variable impairment in behavioral, executive, language, and even motor functions early in the disease course. Each has a unique atrophy pattern on neuroimaging. Commonly, there is accumulation of tau, transactive response DNA binding protein 43 (TDP-43), fusion in sarcoma protein (FUS), and p62 dipeptides. 2In 2011, revised consensus criteria were created for both bvFTD and PPA to incorporate advances in imaging, pathology, and genetics, aiming to improve early diagnostic accuracy. AbstractIn this review, the authors outline a clinical approach to frontotemporal lobar degeneration (FTLD), a term coined to describe a pathology associated with atrophy of the frontal and temporal lobes commonly seen with abnormal protein aggregates. It accounts for $10% of pathologically confirmed dementias. The three clinical syndromes associated with FTLD are jointly classified as frontotemporal dementia (FTD) and include behavioral variant frontotemporal dementia (bvFTD), nonfluent-agrammatic primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA; left: l-svPPA and right: rsvPPA). All syndromes have differential impairment in behavioral (bvFTD; r-svPPA), executive (bvFTD; nfvPPA), and language (nfvPPA; svPPA) functions early in the disease course. With all three there is relative sparing of short-term memory and visuospatial abilities early on, and with the two language syndromes, nfvPPA and svPPA, behavior is also intact. Symptoms are associated with specific atrophy patterns, lending unique imaging signatures to each syndrome (frontal: bvFTD and nfvPPA; temporal: svPPA). Common proteinopathies involve accumulation of tau, transactive response DNA binding protein 43, and fusion in sarcoma protein. Parkinsonism presents in all syndromes, especially cases with tau pathology and MAPT or GRN mutations. nfvPPA often has corticobasal degeneration or progressive supranuclear palsy as the underlying neuropathological substrate. bvFTD co-occurs with motor neuron disease in $15% of cases, and many such cases are due to C9Orf72 mutations. Other common genetic mutations in FTLD involve GRN and MAPT. Behavioral symptoms are best managed by selective serotonin reuptake inhibitors, while atypical antipsychotics should be used with caution given side effects. Promising etiologic treatments include anti-tau antibodies, antisense oligonucleotides, and progranulin enhancers.

Sleep/waking regulation and REM sleep regulation are disrupted in PSP, leading to profound sleep deprivation without recuperation. Our findings suggest a diminished homeostatic sleep drive in PSP. This hyperaroused state is unique and is a severely disabling feature of PSP.

Although the diagnosis of dementia still is primarily based on clinical criteria, neuroimaging is playing an increasingly important role. This is in large part due to advances in techniques that can assist with discriminating between different syndromes. Magnetic resonance imaging remains at the core of differential diagnosis, with specific patterns of cortical and subcortical changes having diagnostic significance. Recent developments in molecular PET imaging techniques have opened the door for not only antemortem but early, even preclinical, diagnosis of underlying pathology. This is vital, as treatment trials are underway for pharmacological agents with specific molecular targets, and numerous failed trials suggest that earlier treatment is needed. This article provides an overview of classic neuroimaging findings as well as new and cutting-edge research techniques that assist with clinical diagnosis of a range of dementia syndromes, with an emphasis on studies using pathologically proven cases.

Background: Recent studies reveal an association between slow-wave sleep (SWS), amyloid- β aggregation, and cognition. Objective: This retrospective study examines whether long-term use of trazodone, an SWS enhancer, is associated with delayed cognitive decline. Methods: We identified 25 regular trazodone users (mean age 75.4±7.5; 9 women, 16 men) who carried a diagnosis of Alzheimer’s dementia, mild cognitive impairment, or normal cognition, and 25 propensity-matched trazodone non-users (mean age 74.5±8.0; 13 women, 12 men), accounting for age, sex, education, type of sleep deficit (hypersomnia, insomnia, parasomnia), diagnosis, and baseline Mini-Mental State Examination (MMSE). Longitudinal group differences in cognitive testing were evaluated through repeated measures tests over an average inter-evaluation interval of four years. Results: Trazodone non-users had 2.6-fold faster decline MMSE (primary outcome) compared to trazodone users, 0.27 (95% confidence interval [CI]: 0.07–0.48) versus 0.70 (95% CI: 0.50–0.90) points per year ( p = 0.023). The observed effects were especially associated with subjective improvement of sleep complaints in post-hoc analyses ( p = 0.0006). Secondary outcomes of other cognitive and functional scores had variable worsening in non-users and varied in significance when accounting for co-administered medications and multiple comparisons. Trazodone effects on MMSE remained significant within participants with AD-predicted pathology, with 2.4-fold faster decline in non-users ( p = 0.038). Conclusions: These results suggest an association between trazodone use and delayed cognitive decline, adding support for a potentially attractive and cost-effective intervention in dementia. Whether the observed relationship of trazodone to cognitive function is causal or an indirect marker of other effects, such as treated sleep disruption, and if such effects are mediated through SWS enhancement requires confirmation through prospective studies.

Insomnia is a common sleep disorder among older adults, and a risk factor for poor physical and mental health. However, the relationship between insomnia and cognitive health is not well understood. Here, we review observational studies that have investigated whether insomnia is associated with deficits in objective cognitive performance and an increased risk of dementia, magnetic resonance imaging studies that have assessed grey matter volumes and white matter microstructure, and interventional studies that have explored whether the treatment of insomnia can improve cognitive outcomes. There are inconsistent findings regarding impaired performance in objective cognitive tests and reduced grey matter volumes, and limited, emerging, evidence that suggests that insomnia is associated with an increased risk of dementia and reduced white matter integrity. Although the interventional literature is still in its infancy, there is some indication that treatment may have an impact on vigilance. Well-powered studies examining sources of heterogeneity are warranted.

Making an accurate diagnosis of schizophrenia and related psychoses early in the course of the disease is important for initiating treatment and counseling patients and families. In this study, we developed classification models for early disease diagnosis using structural MRI (sMRI) and neuropsychological (NP) testing. We used sMRI measurements and NP test results from 28 patients with recent-onset schizophrenia and 47 healthy subjects, drawn from the larger sample of the Mind Clinical Imaging Consortium. We developed diagnostic models based on Linear Discriminant Analysis (LDA) following two approaches; namely, (a) stepwise (STP) LDA on the original measurements, and (b) LDA on variables created through Principal Component Analysis (PCA) and selected using the Humphrey-Ilgen parallel analysis. Error estimation of the modeling algorithms was evaluated by leave-one-out external cross-validation. These analyses were performed on sMRI and NP variables separately and in combination. The following classification accuracy was obtained for different variables and modeling algorithms. sMRI only: (a) STP-LDA: 64.3% sensitivity and 76.6% specificity, (b) PCA-LDA: 67.9% sensitivity and 72.3% specificity. NP only: (a) STP-LDA: 71.4% sensitivity and 80.9% specificity, (b) PCA-LDA: 78.5% sensitivity and 91.5% specificity. Combined sMRI-NP: (a) STP-LDA: 64.3% sensitivity and 83.0% specificity, (b) PCA-LDA: 89.3% sensitivity and 93.6% specificity. (i) Maximal diagnostic accuracy was achieved by combining sMRI and NP variables. (ii) NP variables were more informative than sMRI, indicating that cognitive deficits can be detected earlier than volumetric structural abnormalities. (iii) PCA-LDA yielded more accurate classification than STP-LDA. As these sMRI and NP tests are widely available, they can increase accuracy of early intervention strategies and possibly be used in evaluating treatment response.