Comprehension of acoustically degraded speech in Alzheimer’s disease and primary progressive aphasia (preprint)

ABSTRACT Successful communication in daily life frequently depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, daily hearing measures (such as degraded speech comprehension) in these diseases remain poorly defined. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer’s disease (AD) and 31 patients representing canonical syndromes of primary progressive aphasia (PPA), in relation to 25 healthy age-matched controls. As a model paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into a variable number of frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility. We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients’ brain MR images) were also assessed. Compared with healthy older controls, all patient groups had a significantly higher mean noise-vocoded speech intelligibility threshold, particularly marked in logopenic variant and nonfluent-agrammatic variant PPA and significantly higher in AD than in semantic variant PPA (all p<0.05). Noise-vocoded intelligibility threshold discriminated dementia syndromes (in particular, Alzheimer’s disease) well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with measures of peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in pre-defined regions of interest, impaired noise-vocoded speech comprehension across dementia syndromes was significantly associated (p<0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network widely implicated in processing degraded speech signals. Taken together, our findings suggest that the comprehension of acoustically altered speech captures a central process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications.

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barre syndrome (preprint)

Background Reports of Guillain-Barre Syndrome (GBS) have emerged during the Coronavirus Disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. Methods The epidemiology of GBS cases reported via the UK National Immunoglobulin Database were studied from 2016-2019 and compared to cases reported during the COVID-19 pandemic. For the cohort study, members of the British Peripheral Nerve Society reported all cases of GBS during the pandemic. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases were compared. Results The UK GBS incidence from 2016-2019 was 1.65-1.88 per 100,000 people per year. GBS and COVID-19 incidence varied between regions and did not correlate (r = 0.06, 95% CI -0.56 to 0.63, p=0.86). GBS incidence fell between March and May 2020 compared to the same months of 2016-2019. Forty-seven GBS cases were included in the cohort study (13 definite, 12 probable COVID-19 and 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome. Intubation was more frequent in the COVID-19+ve cohort (7/13, 54% vs 5/22, 23% in COVID negative) thought to be related directly to COVID-19 pulmonary involvement. Conclusions This study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.