Donepezil enhances understanding of degraded speech in Alzheimer's disease

Hardy, Chris; Hwang, Yun Tae; Bond, Rebecca L.; Marshall, Charles R.; Ridha, Basil H.; Crutch, Sebastian J.; Rossor, Martin N.; Warren, Jason D.

doi:10.1002/acn3.471

Cited by 15 publications

(26 citation statements)

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“…Perception of degraded speech is impaired in patients with nfvPPA, svPPA and tAD [ 14 , 15 ], whereas implicit auditory sequence learning and disambiguation of degraded speech are retained in nfvPPA [ 10 , 16 ], albeit with reduced flexibility in using contextual information. Processing degraded sensory stimuli taxes the functional integrity of cortical circuits [ 17 , 18 ], and disorders such as PPA and tAD constitute test cases for exposing such effects because they strike auditory processing networks early and relatively selectively.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, perceptual learning reflects functional brain reorganisation or plasticity; it might therefore help compensate for effects of neurodegeneration [ 19 ]. Adaptation to degraded speech engages areas (such as sensorimotor cortex) beyond classical language and auditory networks [ 20 , 21 ] and may be enhanced by cholinergic stimulation [ 15 ]. Taken together, these considerations suggest that understanding and perceptual learning of degraded speech might constitute a powerful and sensitive probe of neural network integrity and residual plasticity in neurodegenerative syndromes.…”

Section: Introductionmentioning

confidence: 99%

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Retained capacity for perceptual learning of degraded speech in primary progressive aphasia and Alzheimer’s disease

et al. 2018

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BackgroundProcessing of degraded speech is a promising model for understanding communication under challenging listening conditions, core auditory deficits and residual capacity for perceptual learning and cerebral plasticity in major dementias.MethodsWe compared the processing of sine-wave-degraded speech in 26 patients with primary progressive aphasia (non-fluent, semantic, and logopenic variants), 10 patients with typical Alzheimer’s disease and 17 healthy control subjects. Participants were required to identify sine-wave words that were more predictable (three-digit numbers) or less predictable (place names). The change in identification performance within each session indexed perceptual learning. Neuroanatomical associations of degraded speech processing were assessed using voxel-based morphometry.ResultsPatients with non-fluent and logopenic progressive aphasia and typical Alzheimer’s disease showed impaired identification of sine-wave numbers, whereas all syndromic groups showed impaired identification of sine-wave place names. A significant overall identification advantage for numbers over place names was shown by patients with typical Alzheimer’s disease, patients with semantic progressive aphasia and healthy control participants. All syndromic groups showed spontaneous perceptual learning effects for sine-wave numbers. For the combined patient cohort, grey matter correlates were identified across a distributed left hemisphere network extending beyond classical speech-processing cortices.ConclusionsThese findings demonstrate resilience of auditory perceptual learning capacity across dementia syndromes, despite variably impaired perceptual decoding of degraded speech and reduced predictive integration of semantic knowledge. This work has implications for the neurobiology of dynamic sensory processing and plasticity in neurodegenerative diseases and for development of novel biomarkers and therapeutic interventions.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0399-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retained capacity for perceptual learning of degraded speech in primary progressive aphasia and Alzheimer’s disease

et al. 2018

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“…Treatment mainly consists of cognition enhancing medications. These medications include donepezil, [ 9 – 11 ] galantamine, [ 12 – 13 ] memantine, [ 14 – 16 ] and rivastigmine. [ 17 , 18 ] However, all these medications can not cure AD completely.…”

Section: Introductionmentioning

confidence: 99%

Spore powder of Ganoderma lucidum for the treatment of Alzheimer disease

Wang

et al. 2018

Medicine

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Background:This study explored the feasible efficacy and safety of the Spore Powder of Ganoderma Lucidum (SPGL) for treating patients with Alzheimer disease (AD).Methods:Forty-two eligible patients with AD were recruited. These patients were randomly allocated to an intervention group and a control group equally. The patients in the intervention group underwent SPGL, whereas the subjects in the control received placebo. All patients were treated for a total of 6 weeks. The primary outcome was measured by Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog). The secondary outcomes were measured by the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Neuropsychiatric Index (NPI). The adverse events were also recorded during the treatment period.Results:At the end of the treatment, GLSP did not show more encouraging outcomes in symptoms improvement, measured by the ADAS-cog (P = .31), and NPI (P = .79); and quality of life enhancement, measured by the WHOQOL-BREF (physical, P = .62; psychological, P = .69; social relationships, P = .75; environment, P = .82; overall quality of life, P = .74), compared with the control group. In addition, all adverse events were mild, and no significant differences were found between 2 groups.Conclusion:The results of this study did not find the promising efficacy of SPGL for the treatment of AD after 6-week treatment. It may be because of the relative short-term of intervention. Future clinical trials with larger sample size and longer treatment period are urgently needed.

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“…Any attribution of “benefit” to DAF will need to take into account its translatability to natural communication in daily life. However, analogously with other forms of speech signal distortion 60 , DAF might constitute a novel target for cholinergic and other pharmacological manipulations designed to restore sensitivity to auditory feedback in the degenerating language network.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of Speech Output to Delayed Auditory Feedback in Primary Progressive Aphasias

Hardy¹,

Bond²,

Jaisin³

et al. 2018

Front. Neurol.

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Delayed auditory feedback (DAF) is a classical paradigm for probing sensori-motor interactions in speech output and has been studied in various disorders associated with speech dysfluency and aphasia. However, little information is available concerning the effects of DAF on degenerating language networks in primary progressive aphasia: the paradigmatic “language-led dementias.” Here we studied two forms of speech output (reading aloud and propositional speech) under natural listening conditions (no feedback delay) and under DAF at 200 ms, in a cohort of 19 patients representing all major primary progressive aphasia syndromes vs. healthy older individuals and patients with other canonical dementia syndromes (typical Alzheimer's disease and behavioral variant frontotemporal dementia). Healthy controls and most syndromic groups showed a quantitatively or qualitatively similar profile of reduced speech output rate and increased speech error rate under DAF relative to natural auditory feedback. However, there was no group effect on propositional speech output rate under DAF in patients with nonfluent primary progressive aphasia and logopenic aphasia. Importantly, there was considerable individual variation in DAF sensitivity within syndromic groups and some patients in each group (though no healthy controls) apparently benefited from DAF, showing paradoxically increased speech output rate and/or reduced speech error rate under DAF. This work suggests that DAF may be an informative probe of pathophysiological mechanisms underpinning primary progressive aphasia: identification of “DAF responders” may open up an avenue to novel therapeutic applications.

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Donepezil enhances understanding of degraded speech in Alzheimer's disease

Cited by 15 publications

References 20 publications

Retained capacity for perceptual learning of degraded speech in primary progressive aphasia and Alzheimer’s disease

Retained capacity for perceptual learning of degraded speech in primary progressive aphasia and Alzheimer’s disease

Spore powder of Ganoderma lucidum for the treatment of Alzheimer disease

Sensitivity of Speech Output to Delayed Auditory Feedback in Primary Progressive Aphasias

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