Can aerobic exercise protect against dementia?

There are more than 36 million people in the US over the age of 65, and all of them are impacted by the cognitive decline and brain atrophy associated with normal aging and dementia-causing conditions like Alzheimer's disease, Lewy body disease, and vascular dementia. Recently, moderate exercise and improved fitness have been shown to enhance cognition in cognitively normal older persons as well as in individuals who complain of memory difficulty. Additionally, fitness correlates with brain volume in persons who are cognitively normal and those with Alzheimer's disease. Exercise in mouse models causes neurogenesis in the dentate gyrus. This review will discuss animal experiments, epidemiology, limited prospective studies, and biomarker data that make the case that prospective blinded studies are urgently needed to evaluate the role of aerobic exercise in protecting against dementia

Brain MR Spectroscopy Changes Precede Frontotemporal Lobar Degeneration Phenoconversion in Mapt Mutation Carriers.

Background and purposeThe objective of this study was to longitudinally investigate the trajectory of change in 1 H MRS measurements in asymptomatic MAPT mutation carriers who became symptomatic during follow-up, and to determine the time at which the neurochemical alterations accelerated during disease progression.MethodsWe identified eight MAPT mutations carriers who transitioned from asymptomatic to symptomatic disease during follow-up. All participants were longitudinally followed with an average of 7.75 years (range 4-11 years) and underwent two or more single voxel 1 H MRS examinations from the posterior cingulate voxel, with a total of 60 examinations. The rate of longitudinal change for each metabolite was estimated using linear mixed models. A flex point model was used to estimate the flex time point of the change in slope.ResultsThe decrease in the NAA/mI ratio accelerated 2.09 years prior to symptom onset, and continued to decline. A similar trajectory was observed in the presumed glial marker mI/Cr ratio accelerating 1.86 years prior to symptom onset.ConclusionsOur findings support the potential use of longitudinal 1 H MRS for monitoring the neurodegenerative progression in MAPT mutation carriers starting from the asymptomatic stage

A nonsense mutation in PRNP associated with clinical Alzheimer's disease

AbstractHere, we describe a nonsense haplotype in PRNP associated with clinical Alzheimer's disease. The patient presented an early-onset of cognitive decline with memory loss as the primary cognitive problem. Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes

Neuropathologic basis of frontotemporal dementia in progressive supranuclear palsy.

BackgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by neuronal loss in the extrapyramidal system with pathologic accumulation of tau in neurons and glia. The most common clinical presentation of PSP, referred to as Richardson syndrome, is that of atypical parkinsonism with vertical gaze palsy, axial rigidity, and frequent falls. Although cognitive deficits in PSP are often ascribed to subcortical dysfunction, a subset of patients has dementia with behavioral features similar to the behavioral variant of frontotemporal dementia. In this study we aimed to identify the clinical and pathological characteristics of PSP presenting with frontotemporal dementia.MethodsIn this study, we compared clinical and pathologic characteristics of 31 patients with PSP with Richardson syndrome with 15 patients with PSP with frontotemporal dementia. For pathological analysis, we used semiquantitative methods to assess neuronal and glial lesions with tau immunohistochemistry, as well image analysis of tau burden using digital microscopic methods.ResultsWe found greater frontal and temporal neocortical neuronal tau pathology in PSP with frontotemporal dementia compared with PSP with Richardson syndrome. White matter tau pathology was also greater in PSP with frontotemporal dementia than PSP with Richardson syndrome. Genetic and demographic factors were not associated with atypical distribution of tau pathology in PSP with frontotemporal dementia.ConclusionsThe results confirm the subset of cognitive-predominant PSP mimicking frontotemporal dementia in PSP. PSP with frontotemporal dementia has distinct clinical features that differ from PSP with Richardson syndrome, as well as differences in distribution and density of tau pathology. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Evaluation of temporomandibular disorders before and after orthognathic surgery: therapeutic considerations on a sample of 76 patients

Temporomandibular disorders may be associated with dental and facial malformations. The aim of this study is to record the prevalence of TMDs in patients scheduled for orthognathic surgery, reporting the development of TMDs and symptoms during the entire period of the treatment, and demonstrating the benefits of a team effort on this population. MATERIALS AND METHODS: Assessment of temporomandibular status was performed using the RDC/TMD criteria at T0 (prior to orthodontic therapy), T1 (3 months after the surgery), and T2 post-therapeutic cycle (6 to 12 months postoperatively). A total of 76 participants were included in the study; all the patients underwent surgical treatment: 12 had bilateral sagittal split osteotomy, 6 with condylar position devices; 64 had Le Fort I + bilateral sagittal split osteotomy, and 15 with condylar position devices. Results were evaluated with a paired-sample t-test and segmentation analysis. RESULTS: Forty-seven patients were affected by TMDs. At T0, 25 patients experienced TMJ pain, 27 had muscular pain, 31 suffered headaches, 42 had disc dislocation with reduction, and 5 were affected by disc dislocation without reduction. Thirty-five patients had occlusal signs of parafunctions, 8 reported tinnitus, and 7 dizziness. At T1, TMJ pain changed from 33.3% to 4.44%, muscular pain changed from 35.5% to 11.1%, headaches improved from 40% to 6.67%, and disc dislocation from 55.2% to 17.7%. Segmentation analysis highlighted improvement after therapy; 57 patients were considered recovered, 14 improved, none were considered stable, whereas 5 patients demonstrated some worsening, 3 of whom had not presented disc dislocation before surgery. At T2, 71 patients were considered completely recovered or improved. CONCLUSIONS: Our data indicates beyond any doubt that both functional status and pain levels related to TMDs can be significantly improved with a multi-disciplinary approach. We concluded that surgeon's intervention need to be modified in the presence of presurgical TMDs

New insights into atypical Alzheimer's disease in the era of biomarkers

Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease

Normal pressure hydrocephalus, or Hakim syndrome: review and update

This review makes the case that idiopathic normal pressure hydrocephalus (iNPH) is an outdated term because new information indicates that the syndrome is less idiopathic and that the cerebrospinal fluid (CSF) pressure of normal individuals is affected by several factors such as body mass index, age, and sex. Our review updates the epidemiology of iNPH and provides a clinical approach to the management of these patients. All the clinical features of iNPH are common in older individuals, and each has many causes, so the diagnosis is difficult. The first step in reaching an accurate diagnosis is to address the possible contributory factors to the gait abnormality and determine what if any role iNPH may be playing. The two best diagnostic tests are neuroimaging and cerebrospinal fluid (CSF) diversion (large volume lumbar puncture or external lumbar drainage) with pre/post gait evaluation. This review provides an update on the growing evidence that vascular disease, impaired CSF absorption, congenital, and genetic factors all contribute to the pathogenesis of iNPH. We suggest replacing the term iNPH with the term Hakim syndrome (HS) in acknowledgement of the first person to describe this syndrome. Lastly, we discuss the improvements in shunt technology and surgical techniques that have decreased the risks and long-term complications of shunt surgery

Realist evaluation comparison of dementia-friendly communities in England and Netherlands

IntroductionDementia-friendly communities coordinate activities and events which offer social inclusion and participation of people with dementia. Initiatives can include memory cafés, sports, tourist and heritage visits. This study explored how dementia-friendly initiatives are developed and sustained in England drawing comparisons with an equivalent case-study in the Netherlands. MethodsWe present a case study of dementia-friendly initiatives, of one city in England. Selection of this case study was on the basis of being a leading dementia-friendly community. We interviewed a variety of stakeholders, including people with dementia and their care partners, volunteers and staff. Semi-structured interviews were recorded, and transcripts were analysed using qualitative analysis software using a realist evaluation interpretation. Realist theories described within this English case study were compared with those described within the Dutch cases studies.FindingsFive context mechanism outcome configurations were described. The dementia action alliance for the city was a coordinator of initiatives and provided funding and resources. The alliance facilitated advocates to partner with organisations with a shared commitment to plan activities. On the level of individual interactions, staff or volunteers were involved in communicating with local community members which may lead to improvement in awareness. Initiatives had various ways to listen and incorporate views of people with dementia. The five mechanisms identified within the English case study resonated with mechanisms identified within the larger Dutch case study, with differences in contexts due to local policies and practices.ConclusionStrategic coordination is an important factor for development and sustainability. The national policy in England has set the pattern for local structures, while the Dutch approach is ‘bottom-up’ with local leadership. Community advocates and public support were important factors in development of dementia-friendly initiatives in both countries

Intonational Impairment Following Naturally Occurring Callosal Disconnection

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