Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia

Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials

Linguistic biomarkers for the detection of Mild Cognitive Impairment

A timely diagnosis of the prodromal stages of dementia remains a big challenge for healthcare systems: many assessment tools have been proposed over recent years, but the commonest screening instruments are largely unreliable for detecting subtle changes in cognition. The scientific literature contains a rising number of reports about language disturbances at the earliest stages of dementia, a clinical syndrome known as “Mild Cognitive Impairment" (MCI). Here we take advantage of these findings to develop a novel NLP method capable of identifying cognitive frailty at a very early stage by processing Italian spoken productions. This study constitutes a first step in the creation of an automatic tool for non-intrusive, low-cost dementia screening exploiting linguistic biomarkers. Our findings show that acoustic features (i.e., fluency indexes and spectral properties of the voice) are the most reliable parameters for MCI early identification. Moreover, lexical and syntactic features, grabbing the erosion of verbal abilities caused by the pathology, emerge as statistically significant and can support speech traits in the classification process

LANGUAGE DYSFUNCTION IN MOTOR NEURON DISEASE: COGNITIVE FEATURES AND SCREENING SENSITIVITY

Motor neuron disease (MND) is a set of neuromuscular diseases that affect the upper and/or lower motor neurons, resulting in progressive disability. Amyotrophic lateral sclerosis (ALS) and Primary lateral sclerosis (PLS) are two forms of MND that both involve upper motor neuron degeneration, which can also accompany extra-motor changes in cognitive, behavioral, and/or emotional functioning for some individuals. Characterization of the cognitive profile of MND is still evolving, with growing interest in cognitive subtypes. The development of cognitive screens targeted to the MND cognitive profile aim to provide efficient and accurate brief assessments. However, empirical evaluation of tailored MND cognitive screens is needed for cross-validation independent of tests’ original developers. The present study addresses the cognitive profile of MND and the utility of brief cognitive screens with a focus on impairments in the language domain. The two primary aims include: (1) comprehensive assessment and characterization of language dysfunction in MND, and (2) empirical evaluation of brief cognitive screens with regard to detecting language impairments. Forty-one patients with MND (ALS n = 36; PLS n = 5) were administered a comprehensive language battery to classify cognitive impairment (MND/ALSci; Strong et al., 2017) in the language domain and/or verbal fluency. Patients also completed two tailored cognitive screens [ALS Cognitive Behavioral Screen (ALS-CBS), Edinburgh Cognitive and Behavioral ALS Screen (ECAS)] and one general screen (Montreal Cognitive Assessment; MoCA). The current preliminary results suggest language dysfunction in MND is characterized by prominent difficulties with word retrieval (confrontation naming) and/or syntax comprehension. However, evidence of reduced word production resembling nonfluent/agrammatic aphasia was not found. In total, 19.5% of the sample met criteria for MND/ALSci in the language domain (n = 8, all ALS); 22.0% met criteria for MND/ALSci in the verbal fluency domain (n = 9). Patients were classified into three subgroups, those with broad language impairments (ALSci-L n = 4, 9.8%), phonemic fluency impairments (MNDci-VF n = 5, 12.2%), or both impairments (ALSci-L+VF n = 4, 9.8%). Results also revealed existing challenges in accurately classifying patients with language dysfunction using brief cognitive screens. The ECAS Language subscore offered limited classification of broad language impairments in the present MND sample (sensitivity 50%, specificity 70%). Among the broader cognitive screens, sensitivities to language impairments were: ALS-CBS (100%), ECAS ALS-Specific Score (75%), and MoCA (71%). Convergent validity was demonstrated between outcomes on the ALS-CBS and ECAS ALS-Specific Score (rФ = .59). Discriminant validity was also demonstrated between outcomes on ALS-CBS compared to the MoCA (rФ = .11). Future research is needed to assess whether language dysfunction reflects a distinct MND cognitive phenotype(s) and potential relationships with disease prognosis. Naming and syntax comprehension may be fruitful language screening targets for future research

Investigating speech and language impairments in delirium: a preliminary case-control study

<div><p>Introduction</p><p>Language impairment is recognized as as part of the delirium syndrome, yet there is little neuropsychological research on the nature of this dysfunction. Here we hypothesized that patients with delirium show impairments in language formation, coherence and comprehension.</p><p>Methods</p><p>This was a case-control study in 45 hospitalized patients (aged 65–97 years) with delirium, dementia without delirium, or no cognitive impairment (N = 15 per group). DSM-5 criteria were used for delirium. Speech was elicited during (1) structured conversational questioning, and (2) the "Cookie Theft" picture description task. Language comprehension was assessed through standardized verbal and written commands. Interviews were audio-recorded and transcribed.</p><p>Results</p><p>Delirium and dementia groups scored lower on the conversational assessment than the control group (p<0.01, moderate effect sizes (r) of 0.48 and 0.51, resp.). In the Cookie Theft task, the average length of utterances (i.e. unit of speech), indicating language productivity and fluency, distinguished patients with delirium from those with dementia (p<0.01, r = 0.50) and no cognitive impairment (p<0.01, r = 0.55). Patients with delirium performed worse on written comprehension tests compared to cognitively unimpaired patients (p<0.01, r = 0.63), but not compared to the dementia group.</p><p>Conclusions</p><p>Production of spontaneous speech, word quantity, speech content and verbal and written language comprehension are impaired in delirious patients compared to cognitively unimpaired patients. Additionally, patients with delirium produced significantly less fluent speech than those with dementia. These findings have implications for how speech and language are evaluated in delirium assessments, and also for communication with patients with delirium. A study limitation was that the delirium group included patients with co-morbid dementia, which precludes drawing conclusions about the specific language profile of delirium.</p></div

Connected speech as a marker of disease progression in autopsy-proven Alzheimer's disease.

Although an insidious history of episodic memory difficulty is a typical presenting symptom of Alzheimer's disease, detailed neuropsychological profiling frequently demonstrates deficits in other cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer's disease. The aim of the present study was to identify features of connected speech that could be used to examine longitudinal profiles of impairment in Alzheimer's disease. Samples of connected speech were obtained from 15 former participants in a longitudinal cohort study of ageing and dementia, in whom Alzheimer's disease was diagnosed during life and confirmed at post-mortem. All patients met clinical and neuropsychological criteria for mild cognitive impairment between 6 and 18 months before converting to a status of probable Alzheimer's disease. In a subset of these patients neuropsychological data were available, both at the point of conversion to Alzheimer's disease, and after disease severity had progressed from the mild to moderate stage. Connected speech samples from these patients were examined at later disease stages. Spoken language samples were obtained using the Cookie Theft picture description task. Samples were analysed using measures of syntactic complexity, lexical content, speech production, fluency and semantic content. Individual case analysis revealed that subtle changes in language were evident during the prodromal stages of Alzheimer's disease, with two-thirds of patients with mild cognitive impairment showing significant but heterogeneous changes in connected speech. However, impairments at the mild cognitive impairment stage did not necessarily entail deficits at mild or moderate stages of disease, suggesting non-language influences on some aspects of performance. Subsequent examination of these measures revealed significant linear trends over the three stages of disease in syntactic complexity, semantic and lexical content. The findings suggest, first, that there is a progressive disruption in language integrity, detectable from the prodromal stage in a subset of patients with Alzheimer's disease, and secondly that measures of semantic and lexical content and syntactic complexity best capture the global progression of linguistic impairment through the successive clinical stages of disease. The identification of disease-specific language impairment in prodromal Alzheimer's disease could enhance clinicians' ability to distinguish probable Alzheimer's disease from changes attributable to ageing, while longitudinal assessment could provide a simple approach to disease monitoring in therapeutic trials