Defining the presymptomatic phase of frontotemporal dementia

PURPOSE OF REVIEW: Frontotemporal dementia (FTD) is a clinically, pathologically and genetically heterogeneous disorder. Whilst disease modifying therapies trials are mostly focused on the symptomatic phase, future studies will move earlier in the disease aiming to prevent symptom onset. This review summarizes the recent work to better understand this presymptomatic period. RECENT FINDINGS: The presymptomatic phase can be split into preclinical and prodromal stages. The onset of the preclinical phase is defined by the first presence of pathological inclusions of tau, TDP-43 or fused in sarcoma in the brain. Definitive biomarkers of these pathologies do not yet exist for FTD. The prodromal phase is defined by the onset of mild symptoms. Recent work has highlighted the wide phenotypic spectrum that occurs, with the concept of mild cognitive ± behavioural ± motor impairment (MCBMI) being put forward, and additions to scales such as the CDR plus NACC FTLD now incorporating neuropsychiatric and motor symptoms. SUMMARY: It will be important to better characterize the presymptomatic period moving forward and develop robust biomarkers that can be used both for stratification and outcome measures in prevention trials. The work of the FTD Prevention Initiative aims to facilitate this by bringing together data from natural history studies across the world

Study protocol: computerised cognitive testing in a cohort of people with frontotemporal dementia

Introduction: The term frontotemporal dementia (FTD) refers to a heterogeneous group of neurodegenerative disorders affecting the frontal and temporal lobes. Cognitively, impairment of executive function and social cognition predominates across the FTD spectrum, although other domains can be affected. Traditionally, cognition is tested through standard ‘pen and paper’ tasks in FTD. However, recent attempts have been made across other neurodegenerative disorders such as Alzheimer’s disease to develop computerised batteries that allow more accurate and sensitive detection of cognitive impairment. / Methods and analysis: This paper describes the development of a novel battery of tests for a tablet computer, particularly focused on FTD. It consists of 12 different tasks which aim to tap into information processing speed, various aspects of executive function, social cognition, semantic knowledge, calculation and visuospatial skills. Future studies will focus on validating the battery in a healthy control cohort, comparing it against a standard ‘pen and paper’ psychometric battery, and finally testing it within an FTD cohort, including those with genetic forms of FTD where we will be able to assess its ability to detect very early cognitive deficits prior to the onset of symptoms. / Ethics and dissemination: Normative data will be produced in the initial validation study (approved by the UCL Ethics Committee, project ID 17691/002) and will be made available online

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived. In fact, “poor” response to levodopa forms part of the NINDS-SPSP criteria for the diagnosis of PSP and consensus criteria for the diagnosis of CBD (Lang Mov Disord. 20 Suppl 1:S83–91, 2005; Litvan et al. Neurology. 48:119–25, 1997; Armstrong et al. Neurology. 80(5):496–503, 2013). There is some evidence that intrasalivery gland botulinum toxin is useful in managing problematic sialorrhea and that intramuscular botulinum toxin and baclofen are helpful in reducing dystonia, including blepharospasm. Benzodiazepines may also be useful in managing dystonia. Myoclonus may be managed using levetiracetam and benzodiazepines. Pharmacological agents licensed for Alzheimer’s disease (such as acetylcholinesterase inhibitors and N-Methyl-D-aspartate receptor antagonists) have been used off-label in PSP, CBD, and other tauopathies with the aim of improving cognition; however, there is limited evidence that they are effective and risk of adverse effects may outweigh benefits. The use of atypical antipsychotics for behavioural symptoms is not recommended in the elderly or those with demetia associated conditions and most antipsychotics will worsen Parkinsonism. Antidepressants may be useful for behavioral symptoms and depression but are often poorly tolerated due to adverse effects. In the absence of an effective drug treatment to target the underlying cause of CBD and PSP, management should focus on optimizing quality of life, relieving symptoms and assisting patients with their activities of daily living (ADL). Patients should be managed by a multidisciplinary team consisting of neurologists, physiotherapists (PT), occupational therapists (OT), speech and language therapists (SALT), dieticians, ophthalmologists, psychologists, and palliative care specialists

Structural neuroanatomy of face processing in frontotemporal lobar degeneration

Impairments of face processing occur frequently in frontotemporal lobar degeneration (FTLD) but the neuroanatomical basis for these deficits has seldom been studied systematically. Here a prospective voxel based morphometry study is described addressing the neuroanatomy of two key dimensions of face processing—face identification and facial emotion recognition—in a single cohort of 32 patients with FTLD (19 with frontal variant and 13 with temporal variant FTLD). For the FTLD group as a whole, face identification was positively associated with grey matter in the right anterior fusiform gyrus while recognition of angry expressions was positively associated with grey matter in the bilateral insula cortex. FTLD provides a perspective on the neuroanatomy of face processing that is complementary to focal lesion and normal functional imaging work

Exploring experiences and needs of spousal carers of people with behavioural variant frontotemporal dementia (bvFTD) including those with familial FTD (fFTD): a qualitative study

INTRODUCTION: Carers of people with frontotemporal dementia (FTD) experience greater challenges than carers of people with other dementias due to the younger age of onset and the challenging presentation of symptoms. The aim of the present study was to explore experiences of spousal carers of people with bvFTD, including those with the familial form of the disease (fFTD). METHOD: Fourteen qualitative interviews were analysed using an inductive approach to Thematic Analysis to understand experiences of spousal carers of people with bvFTD including those with fFTD. RESULTS: Five main themes were identified including: a) The "Constant Battle" - A journey toward an FTD diagnosis, b) Shock, Relief and Fear - Challenges persist post diagnosis, c) The "Life Altering" impact - The loss of the spousal relationship and shifting roles, d) Adapting, Managing Symptoms and Receiving Carer Support, e) Lack of General Knowledge - Barriers to support. CONCLUSIONS: Healthcare professionals should be educated on the initial presentations of FTD, to enable carers and families receive timely diagnosis and appropriate support. Future research should investigate the impact of fFTD on carers and families, to explore positive or meaningful experiences in caring, as well as theory-driven research to identify helpful coping strategies for carers of people with FTD

Looking beneath the surface: the importance of subcortical structures in frontotemporal dementia.

Funder: National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research UnitFunder: Alzheimer's Research UK, Brain Research Trust and The Wolfson FoundationFunder: Medical Research CouncilFunder: Alzheimer’s Society and Alzheimer’s Research UKFunder: NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research FacilityFunder: DRI LtdWhilst initial anatomical studies of frontotemporal dementia focussed on cortical involvement, the relevance of subcortical structures to the pathophysiology of frontotemporal dementia has been increasingly recognized over recent years. Key structures affected include the caudate, putamen, nucleus accumbens, and globus pallidus within the basal ganglia, the hippocampus and amygdala within the medial temporal lobe, the basal forebrain, and the diencephalon structures of the thalamus, hypothalamus and habenula. At the most posterior aspect of the brain, focal involvement of brainstem and cerebellum has recently also been shown in certain subtypes of frontotemporal dementia. Many of the neuroimaging studies on subcortical structures in frontotemporal dementia have been performed in clinically defined sporadic cases. However, investigations of genetically- and pathologically-confirmed forms of frontotemporal dementia are increasingly common and provide molecular specificity to the changes observed. Furthermore, detailed analyses of sub-nuclei and subregions within each subcortical structure are being added to the literature, allowing refinement of the patterns of subcortical involvement. This review focuses on the existing literature on structural imaging and neuropathological studies of subcortical anatomy across the spectrum of frontotemporal dementia, along with investigations of brain-behaviour correlates that examine the cognitive sequelae of specific subcortical involvement: it aims to 'look beneath the surface' and summarize the patterns of subcortical involvement have been described in frontotemporal dementia

Structural neuroanatomy of tinnitus and hyperacusis in semantic dementia

Introduction Tinnitus and hyperacusis are common symptoms of excessive auditory perception in the general population; however, their anatomical substrates and disease associations continue to be defined. Patients with semantic dementia (SemD) frequently repor