The Reliability and Clinical Validation of Automatically-Derived Verbal Memory Features of the Verbal Learning Test in Early Diagnostics of Cognitive Impairment.

BACKGROUND: Previous research has shown that verbal memory accurately measures cognitive decline in the early phases of neurocognitive impairment. Automatic speech recognition from the verbal learning task (VLT) can potentially be used to differentiate between people with and without cognitive impairment. OBJECTIVE: Investigate whether automatic speech recognition (ASR) of the VLT is reliable and able to differentiate between subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: The VLT was recorded and processed via a mobile application. Following, verbal memory features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to distinguish between participants with SCD versus MCI/dementia. RESULTS: The ICC for inter-rater reliability between the clinical and automatically derived features was 0.87 for the total immediate recall and 0.94 for the delayed recall. The full model including the total immediate recall, delayed recall, recognition count, and the novel verbal memory features had an AUC of 0.79 for distinguishing between participants with SCD versus MCI/dementia. The ten best differentiating VLT features correlated low to moderate with other cognitive tests such as logical memory tasks, semantic verbal fluency, and executive functioning. CONCLUSIONS: The VLT with automatically derived verbal memory features showed in general high agreement with the clinical scoring and distinguished well between SCD and MCI/dementia participants. This might be of added value in screening for cognitive impairment.

Contributions of Vascular Burden and Amyloid Abnormality to Cognitive Decline in Memory Clinic Patients.

Background: Alzheimer's disease pathology and vascular burden are highly prevalent and often co-occur in elderly. It remains unclear how both relate to cognitive decline. Objective: To investigate whether amyloid abnormality and vascular burden synergistically contribute to cognitive decline in a memory clinic population. Methods: We included 227 patients from Maastricht and Aachen memory clinics. Amyloid abnormality (A+) was defined by CSF Aß42 using data-driven cut-offs. Vascular burden (V+) was defined as having moderate to severe white matter hyperintensities, or any microbleeds, macrohemorrhage or infarcts on MRI. Longitudinal change in global cognition, memory, processing speed, executive functioning, and verbal fluency was analysed across the A-V-, A-V+, A+V-, A+V+ groups by linear mixed models. Additionally, individual MRI measures, vascular risk and vascular disease were used as V definitions. Results: At baseline, the A+V+ group scored worse on global cognition and verbal fluency compared to all other groups, and showed worse memory compared to A-V+ and A-V- groups. Over time (mean 2.7+ - 1.5 years), A+V+ and A+V- groups showed faster global cognition decline than A-V+ and A-V- groups. Only the A+V- group showed decline on memory and verbal fluency. The A-V+ group did not differ from the A-V- group. Individual MRI vascular measures only indicated an independent association of microbleeds with executive functioning decline. Findings were similar using other V definitions. Conclusions: Our study demonstrates that amyloid abnormality predicts cognitive decline independent from vascular burden in a memory clinic population. Vascular burden shows a minor contribution to cognitive decline in these patients. This has important prognostic implications.

Transferring people with dementia to severe challenging behavior specialized units, an in-depth exploration.

OBJECTIVES: One of the main reasons for people with dementia to move to a dementia special care unit of a nursing home is challenging behavior. This behavior is often difficult to manage, and in the Netherlands, residents are sometimes relocated to a severe challenging behavior specialized unit. However, relocation often comes with trauma and should be prevented if possible. This study aimed to investigate the patient- and context-related reasons for these relocations. METHODS: Qualitative multiple case study using individual (n = 15) and focus group interviews (n = 4 with n = 20 participants) were held with elderly care physicians, physician assistants, psychologists, nursing staff members, and relatives involved with people with dementia and severe challenging behavior who had been transferred to a severe challenging behavior specialized unit. Audio recordings were transcribed and analyzed with thematic analysis, including directed content analysis. RESULTS: After five cases, data-saturation occurred. The thematic analysis identified three main processes: increasing severity of challenging behavior, increasing realization that the clients' needs cannot be met, and an increasing burden of nursing staff. The interaction between these processes, triggered mainly by a life-threatening situation, led to nursing staff reaching their limits, resulting in relocation of the client. CONCLUSION: Our study resulted in a conceptual framework providing insight into reasons for relocation in cases of severe challenging behavior. To prevent relocation, the increasing severity of challenging behavior, increasing burden on nursing staff, and increasing realization that the clients' needs cannot be met need attention.

Validation of an Automated Speech Analysis of Cognitive Tasks within a Semiautomated Phone Assessment.

Introduction: We studied the accuracy of the automatic speech recognition (ASR) software by comparing ASR scores with manual scores from a verbal learning test (VLT) and a semantic verbal fluency (SVF) task in a semiautomated phone assessment in a memory clinic population. Furthermore, we examined the differentiating value of these tests between participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We also investigated whether the automatically calculated speech and linguistic features had an additional value compared to the commonly used total scores in a semiautomated phone assessment. Methods: We included 94 participants from the memory clinic of the Maastricht University Medical Center+ (SCD N = 56 and MCI N = 38). The test leader guided the participant through a semiautomated phone assessment. The VLT and SVF were audio recorded and processed via a mobile application. The recall count and speech and linguistic features were automatically extracted. The diagnostic groups were classified by training machine learning classifiers to differentiate SCD and MCI participants. Results: The intraclass correlation for inter-rater reliability between the manual and the ASR total word count was 0.89 (95% CI 0.09-0.97) for the VLT immediate recall, 0.94 (95% CI 0.68-0.98) for the VLT delayed recall, and 0.93 (95% CI 0.56-0.97) for the SVF. The full model including the total word count and speech and linguistic features had an area under the curve of 0.81 and 0.77 for the VLT immediate and delayed recall, respectively, and 0.61 for the SVF. Conclusion: There was a high agreement between the ASR and manual scores, keeping the broad confidence intervals in mind. The phone-based VLT was able to differentiate between SCD and MCI and can have opportunities for clinical trial screening.

The Accuracy of Speech and Linguistic Analysis in Early Diagnostics of Neurocognitive Disorders in a Memory Clinic Setting.

OBJECTIVE: To investigate whether automatic analysis of the Semantic Verbal Fluency test (SVF) is reliable and can extract additional information that is of value for identifying neurocognitive disorders. In addition, the associations between the automatically derived speech and linguistic features and other cognitive domains were explored. METHOD: We included 135 participants from the memory clinic of the Maastricht University Medical Center+ (with Subjective Cognitive Decline [SCD; N = 69] and Mild Cognitive Impairment [MCI]/dementia [N = 66]). The SVF task (one minute, category animals) was recorded and processed via a mobile application, and speech and linguistic features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to differentiate SCD and MCI/dementia participants. RESULTS: The intraclass correlation for interrater reliability between the clinical total score (golden standard) and automatically derived total word count was 0.84. The full model including the total word count and the automatically derived speech and linguistic features had an Area Under the Curve (AUC) of 0.85 for differentiating between people with SCD and MCI/dementia. The model with total word count only and the model with total word count corrected for age showed an AUC of 0.75 and 0.81, respectively. Semantic switching correlated moderately with memory as well as executive functioning. CONCLUSION: The one-minute SVF task with automatically derived speech and linguistic features was as reliable as the manual scoring and differentiated well between SCD and MCI/dementia. This can be considered as a valuable addition in the screening of neurocognitive disorders and in clinical practice.

The Role of Vascular Risk Factors in Biomarker-Based AT(N) Groups: A German-Dutch Memory Clinic Study.

BACKGROUND: The relation between vascular risk factors (VRFs) and Alzheimer's disease (AD) is important due to possible pathophysiological association. OBJECTIVE: To assess the prevalence of VRFs in biomarker-based AT(N) groups and the associations between VRFs, AD cerebrospinal fluid (CSF) biomarkers, brain magnetic resonance imaging (MRI), and cognition in clinical context. METHODS: We included patients from two memory clinics in University Hospital Aachen (Germany) and Maastricht University Medical Centre (The Netherlands). Subjects were older than 45 years and had available data on demographics, VRFs, CSF AD biomarkers, and MRI. We categorized individuals in normal AD biomarkers, non-AD change, and AD-continuum groups based on amyloid (A), tau (T), and neurodegeneration (N) status in CSF and MRI. Regression models were corrected for age, sex, and site. RESULTS: We included 838 participants (mean age 68.7, 53.2% male, mean MMSE 24.9). The most common VRFs were smoking (60.9%), hypertension (54.6%), and dyslipidemia (37.8%). Alcohol abuse and smoking were most frequent in the non-AD-change group, and coronary heart disease and carotid artery stenosis in the AD continuum group. Higher rates of depression were found in the normal AD biomarkers group. Parietal atrophy and cortical microbleeds were specific for the AD continuum group. Carotid artery stenosis was associated with pathological Aß42 and T-tau values, and diabetes and alcohol abuse were associated with worse medial temporal atrophy and atrial fibrillation, with worse cognition. CONCLUSION: VRFs are common in memory clinic patients, showing differences across the AT(N) biomarker groups. This is important for prevention and individualized treatment of dementia.

Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer's disease dementia.

OBJECTIVES: To examine trajectories of depression and apathy over a 5-year follow-up period in (prodromal) Alzheimer's disease (AD), and to relate these trajectories to AD biomarkers. METHODS: The trajectories of depression and apathy (measured with the Neuropsychiatric Inventory or its questionnaire) were separately modeled using growth mixture models for two cohorts (National Alzheimer's Coordinating Center, NACC, n = 22 760 and Alzheimer's Disease Neuroimaging Initiative, ADNI, n = 1 733). The trajectories in ADNI were associated with baseline CSF AD biomarkers (Aß42, t-tau, and p-tau) using bias-corrected multinomial logistic regression. RESULTS: Multiple classes were identified, with the largest classes having no symptoms over time. Lower Aß42 and higher tau (ie, more AD pathology) was associated with increased probability of depression and apathy over time, compared to classes without symptoms. Lower Aß42 (but not tau) was associated with a steep increase of apathy, whereas higher tau (but not Aß42 ) was associated with a steep decrease of apathy. DISCUSSION: The trajectories of depression and apathy in individuals on the AD spectrum are associated with AD biomarkers.

The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum.

OBJECTIVE: To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. METHODS: Data from two large cohort studies, the Dutch Parelsnoer Institute - Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N = 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of Aß42, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. RESULTS: Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF Aß42, higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF Aß42 and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. CONCLUSION: The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.

Determinants of Cross-Sectional and Longitudinal Health-Related Quality of Life in Memory Clinic Patients Without Dementia.

OBJECTIVE: To identify determinants within 3 different domains (ie, somatic comorbidities, cognitive functioning, and neuropsychiatric symptoms [NPS]) of health-related quality of life (HRQoL) over time in memory clinic patients without dementia. METHODS: This longitudinal multicenter cohort study with a 3-year observation period recruited 315 individuals (age: 69.8 ± 8.6, 64.4% males, Mini-Mental State Examination score 26.9 ± 2.6). A multivariable explanatory model was built using linear mixed effects models (forward selection per domain) to select determinants for self-perceived HRQoL over time, as measured by the EuroQoL-5D visual analogue scale (EQ VAS). RESULTS: Mean HRQoL at study entry was 69.4 ± 15.6. The presence of agitation, appetite and eating abnormalities, and eyes/ears/nose (ie, sensory impairment) comorbidities were associated with a change in HRQoL over time. Agitation was most strongly associated with HRQoL over time. CONCLUSIONS: The association of somatic comorbidities and NPS in memory clinic patients with course of HRQoL shows that these should receive more awareness, detection, and monitoring by clinicians.

Affective symptoms and AT(N) biomarkers in mild cognitive impairment and Alzheimer's disease: A systematic literature review.

INTRODUCTION: Alzheimer's disease (AD) biomarkers such as amyloid, p-tau and neuronal injury markers have been associated with affective symptoms in cognitively impaired individuals, but results are conflicting. METHODS: CINAHL, Embase, PsycINFO and PubMed were searched for studies evaluating AD biomarkers with affective symptoms in mild cognitive impairment and AD dementia. Studies were classified according to AT(N) research criteria. RESULT: Forty-five abstracts fulfilled eligibility criteria, including in total 8,293 patients (41 cross-sectional studies and 7 longitudinal studies). Depression and night-time behaviour disturbances were not related to AT(N) markers. Apathy was associated with A markers (PET, not CSF). Mixed findings were reported for the association between apathy and T(N) markers; anxiety and AT(N) markers; and between agitation and irritability and A markers. Agitation and irritability were not associated with T(N) markers. DISCUSSION: Whereas some AD biomarkers showed to be associated with affective symptoms in AD, most evidence was inconsistent. This is likely due to differences in study design or heterogeneity in affective symptoms. Directions for future research are given.

Working Memory Training in Professional Football Players: A Small-Scale Descriptive Feasibility Study-The Importance of Personality, Psychological Well-Being, and Motivational Factors.

BACKGROUND: Working memory training (WMT) programs can improve working memory (WM). In football players, this could lead to improved performance on the pitch. METHOD: Eighteen professional football players of Maatschappelijke Voetbal Vereniging Maastricht (MVV) participated and followed an online, computerized WMT program. Neuropsychological performance, psychological wellbeing, self-efficacy, and football skills (Loughborough Soccer Passing Test; LSPT) were assessed at three time points, before and after WMT and at three-month follow-up. Descriptive data are reported. RESULTS: Baseline characteristics were roughly similar for both groups. Participants performed better on the trained WM tasks, but performance for other neuropsychological test measures or the LSPT did not change. Low compliance rates were observed, showing differences in personality and well-being between compliers and non-compliers. CONCLUSIONS: WMT is not a feasible and effective strategy to improve non-trained cognitive measures and football performance. However, this study indicates that it is important to take individual characteristics into account.

Apolipoprotein E and affective symptoms in mild cognitive impairment and Alzheimer's disease dementia: A systematic review and meta-analysis.

OBJECTIVE: APOE status has been associated to affective symptoms in cognitively impaired subjects, with conflicting results. METHODS: Databases CINAHL, Embase, PsychINFO and PubMed were searched for studies evaluating APOE genotype with affective symptoms in MCI and AD dementia. Symptoms were meta-analyzed separately and possible sources of heterogeneity were examined. RESULTS: Fifty-three abstracts fulfilled the eligibility criteria. No association was found between the individual symptoms and APOE ε4 carriership or zygosity. For depression and anxiety, only pooled unadjusted estimates showed positive associations with between-study heterogeneity, which could be explained by variation in study design, setting and way of symptom assessment. CONCLUSIONS: There is no evidence that APOE ε4 carriership or zygosity is associated with the presence of depression, anxiety, apathy, agitation, irritability or sleep disturbances in cognitively impaired subjects. Future research should shift its focus from this single polymorphism to a more integrated view of other biological factors.