Teaching Neuro Images: Nonfluent variant primary progressive aphasia: A distinctive clinico-Anatomical syndrome

A 66-year-old woman presented with 4 years of progressive speech difficulty. She had nonfluent speech with phonemic errors but intact single-word comprehension and object knowledge. Her grammar was impaired in both speech and writing, and she exhibited orofacial apraxia. A clinico-radiologic (see figure) diagnosis of nonfluent variant primary progressive aphasia was made

Teaching NeuroImages: Nonfluent variant primary progressive aphasia: A distinctive clinico-anatomical syndrome

A 66-year-old woman presented with 4 years of progressive speech difficulty. She had nonfluent speech with phonemic errors but intact single-word comprehension and object knowledge. Her grammar was impaired in both speech and writing, and she exhibited orofacial apraxia. A clinico-radiologic (see figure) diagnosis of nonfluent variant primary progressive aphasia was made

Hearing and dementia: from ears to brain

The association between hearing impairment and dementia has emerged as a major public health challenge, with significant opportunities for earlier diagnosis, treatment and prevention. However, the nature of this association has not been defined. We hear with our brains, particularly within the complex soundscapes of everyday life: neurodegenerative pathologies target the auditory brain, and are therefore predicted to damage hearing function early and profoundly. Here we present evidence for this proposition, based on structural and functional features of auditory brain organization that confer vulnerability to neurodegeneration, the extensive, reciprocal interplay between ‘peripheral’ and ‘central’ hearing dysfunction, and recently characterized auditory signatures of canonical neurodegenerative dementias (Alzheimer’s disease, Lewy body disease and frontotemporal dementia). Moving beyond any simple dichotomy of ear and brain, we argue for a reappraisal of the role of auditory cognitive dysfunction and the critical coupling of brain to peripheral organs of hearing in the dementias. We call for a clinical assessment of real-world hearing in these diseases that moves beyond pure tone perception to the development of novel auditory ‘cognitive stress tests’ and proximity markers for the early diagnosis of dementia and management strategies that harness retained auditory plasticit

Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

PURPOSE OF REVIEW: The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable challenges to clinicians and researchers. RECENT FINDINGS: Here, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering 'fragmentary' syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed. New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies

Agnosia for bird calls

The cognitive organisation of nonverbal auditory knowledge remains poorly defined. Deficits of environmental sound as well as word and visual object knowledge are well-recognised in semantic dementia. However, it is unclear how auditory cognition breaks down in this disorder and how this relates to deficits in other knowledge modalities. We had the opportunity to study a patient with a typical syndrome of semantic dementia who had extensive premorbid knowledge of birds, allowing us to assess the impact of the disease on the processing of auditory in relation to visual and verbal attributes of this specific knowledge category. We designed a novel neuropsychological test to probe knowledge of particular avian characteristics (size, behaviour [migratory or nonmigratory], habitat [whether or not primarily water-dwelling]) in the nonverbal auditory, visual and verbal modalities, based on a uniform two-alternative-forced-choice procedure. The patient's performance was compared to healthy older individuals of similar birding experience. We further compared his performance on this test of bird knowledge with his knowledge of familiar human voices and faces. Relative to healthy birder controls, the patient showed marked deficits of bird call and bird name knowledge but relatively preserved knowledge of avian visual attributes and retained knowledge of human voices and faces. In both the auditory and visual modalities, his knowledge of the avian characteristics of size and behaviour was intact whereas his knowledge of the associated characteristic of habitat was deficient. This case provides further evidence that nonverbal auditory knowledge has a fractionated organisation that can be differentially targeted in semantic dementia

From principles to practice: a spatial approach to systematic conservation planning in the deep sea

Increases in the demand and price for industrial metals, combined with advances in technological capabilities have now made deep-sea mining more feasible and economically viable. In order to balance economic interests with the conservation of abyssal plain ecosystems, it is becoming increasingly important to develop a systematic approach to spatial management and zoning of the deep sea. Here, we describe an expert-driven systematic conservation planning process applied to inform science-based recommendations to the International Seabed Authority for a system of deep-sea marine protected areas (MPAs) to safeguard biodiversity and ecosystem function in an abyssal Pacific region targeted for nodule mining (e.g. the Clarion-Clipperton fracture zone, CCZ). Our use of geospatial analysis and expert opinion in forming the recommendations allowed us to stratify the proposed network by biophysical gradients, maximize the number of biologically unique seamounts within each subregion, and minimize socioeconomic impacts. The resulting proposal for an MPA network (nine replicate 400 × 400 km MPAs) covers 24% (1 440 000 km(2)) of the total CCZ planning region and serves as example of swift and pre-emptive conservation planning across an unprecedented area in the deep sea. As pressure from resource extraction increases in the future, the scientific guiding principles outlined in this research can serve as a basis for collaborative international approaches to ocean management

Teaching NeuroImages: Nonfluent variant primary progressive aphasia A distinctive clinico-anatomical syndrome

The Dementia Research Centre is grateful for the support of the NIHR Queen Square Dementia Biomedical Research Unit. The Article Processing Charge was paid by Wellcome Trust

Frontotemporal Dementia: A Clinical Review.

Frontotemporal dementias are a clinically, neuroanatomically, and pathologically diverse group of diseases that collectively constitute an important cause of young-onset dementia. Clinically, frontotemporal dementias characteristically strike capacities that define us as individuals, presenting broadly as disorders of social behavior or language. Neurobiologically, these diseases can be regarded as "molecular nexopathies," a paradigm for selective targeting and destruction of brain networks by pathogenic proteins. Mutations in three major genes collectively account for a substantial proportion of behavioral presentations, with far-reaching implications for the lives of families but also potential opportunities for presymptomatic diagnosis and intervention. Predicting molecular pathology from clinical and radiological phenotypes remains challenging; however, certain patterns have been identified, and genetically mediated forms of frontotemporal dementia have spearheaded this enterprise. Here we present a clinical roadmap for diagnosis and assessment of the frontotemporal dementias, motivated by our emerging understanding of the mechanisms by which pathogenic protein effects at the cellular level translate to abnormal neural network physiology and ultimately, complex clinical symptoms. We conclude by outlining principles of management and prospects for disease modification

Inappropriate trusting behaviour in dementia

BACKGROUND: Inappropriate trusting behaviour may have significant social, financial and other consequences for people living with dementia. However, its clinical associations and predictors have not been clarified. Here we addressed this issue in canonical syndromes of frontotemporal dementia (FTD) and Alzheimer’s disease (AD). METHODS: In 34 patients with AD and 73 with FTD (27 behavioural variant (bv)FTD, 22 semantic variant primary progressive aphasia (svPPA), 24 nonfluent/agrammatic variant (nfv)PPA) we recorded inappropriate trusting and other abnormal socio-emotional behaviours using a semi-structured caregiver survey. Patients were comprehensively characterised using a general cognitive assessment and the Revised Self-Monitoring Scale (RSMS; an informant index of socioemotional awareness). RESULTS: Inappropriate trusting was more frequent in svPPA (55%) and bvFTD (44%) than nfvPPA (17%) or AD (24%). After adjusting for age, sex, education and Mini-Mental State Examination (MMSE) score, inappropriate trusting was significantly more likely in svPPA (odds ratio 3.61; 95% confidence interval 1.41–8.75) and bvFTD (3.01, 1.23–6.65) than AD. Significant predictors of inappropriate trusting comprised apathy in svPPA, disinhibition and altered pain responsiveness in bvFTD, and lower MMSE and RSMS (self-presentation) scores in AD. CONCLUSION: Dementia syndromes vary in prevalence and predictors of abnormal trusting behaviour, with implications for clinical counselling and safeguarding