Driving Automation for Older Adults with Preclinical Alzheimer's Disease.

INTRODUCTION: Older adults with preclinical Alzheimer's disease (AD) show changes in on-road driving performance. The impact of preclinical AD on using automated vehicle (AV) technology is unknown. The aim was to evaluate safety and cognitive workload while operating AV technology in drivers with preclinical AD. INTRODUCTION: This cross-sectional study included 40 participants: 19 older adults (age 74.16 ± 4.78; MOCA scores 26.42 ± 2.52) with preclinical AD, evidenced by elevated cortical beta-amyloid; and 21 controls (age 73.81 ± 5.62; MOCA scores 28.24 ± 1.67). All participants completed two scenarios in a driving simulator. Scenario 1 included conditional automation with an emergency event that required a manual take-over maneuver. Scenario 2 was identical but with a cognitive distractor task. Emergency response time was the main safety outcome measure. Cognitive workload was calculated using moment-to-moment changes in pupillary size and converted into an Index of Cognitive Activity (ICA). Mann-Whitney U and independent t tests were used to compare group differences. RESULTS: Emergency response times were similar between drivers with preclinical AD and controls in scenario 1 (20.85 s ± 1.08 vs. 20.52 s ± 3.18; p = 0.83) and scenario 2 (14.83 s ± 7.37 vs. 13.45 s ± 10.43; p = 0.92). Likewise, no differences were found in ICA between drivers with preclinical AD and controls in scenario 1 (0.34 ± 0.08 vs. 0.33 ± 0.17; p = 0.74) or scenario 2 (0.30 ± 0.07 vs. 0.29 ± 0.17; p = 0.93). CONCLUSIONS: Older drivers with preclinical AD may safely operate AV technology, without increased response times or cognitive workload. Future on-road studies with AV technology should confirm these preliminary results in drivers with preclinical AD.

Effect of Cognitive Reserve on Physiological Measures of Cognitive Workload in Older Adults with Cognitive Impairments.

BACKGROUND: Cognitive reserve may protect against cognitive decline. OBJECTIVE: This cross-sectional study investigated the association between cognitive reserve and physiological measures of cognitive workload in older adults with cognitive impairment. METHODS: 29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MoCA: 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MoCA: 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve. Linear mixed models evaluated the main effects of cognitive status, CRIq, and the interaction effect of CRIq by cognitive status on ERP and ICA. RESULTS: The interaction effect of CRIq total score by cognitive status on P3 ERP and ICA was not significant. However, higher CRIq total scores were associated with lower ICA (p = 0.03). The interaction effects of CRIq subscores showed that Work Activity affected P3 amplitude (p = 0.03) and ICA (p = 0.03) differently between older adults with and without cognitive impairments. Similarly, Education affected ICA (p = 0.02) differently between the two groups. No associations were observed between CRIq and P3 latency. CONCLUSION: Specific components of cognitive reserve affect cognitive workload and neural efficiency differently in older adults with and without cognitive impairments.

EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid.

BACKGROUND: Although growing evidence links beta-amyloid (Aß) and neuronal hyperexcitability in preclinical mouse models of Alzheimer's disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aß (Aß+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event-related power between CNAß+ and CNAß-. METHODS: Seventeen CNAß+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAß- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget-target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 amplitude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aß standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. RESULTS: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAß+ group (P = 0.048). Similarly, power was lower in the delta band for nontargets at Fz in the CNAß+ participants (P = 0.04). The CNAß+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aß SUVR and the latency of the 1-back (r = - 0.69; P = 0.003) and 2-back (r = - 0.69; P = 0.004) of the task difference effect at channel Fz in the CNAß+ group. CONCLUSIONS: Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.

Exercise interventions for older adults with Alzheimer's disease: a systematic review and meta-analysis protocol.

BACKGROUND: The growing societal and economic impact of Alzheimer's disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations. METHODS: This systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol. DISCUSSION: This review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020175016 .

Psychometric Properties of NASA-TLX and Index of Cognitive Activity as Measures of Cognitive Workload in Older Adults.

Cognitive workload is increasingly recognized as an important determinant of performance in cognitive tests and daily life activities. Cognitive workload is a measure of physical and mental effort allocation to a task, which can be determined through self-report or physiological measures. However, the reliability and validity of these measures have not been established in older adults with a wide range of cognitive ability. The aim of this study was to establish the test-retest reliability of the National Aeronautics and Space Administration Task Load Index (NASA-TLX) and Index of Cognitive Activity (ICA), extracted from pupillary size. The convergent validity of these measures against event-related potentials (ERPs) was also investigated. A total of 38 individuals with scores on the Montreal Cognitive Assessment ranging between 17 and 30 completed a working memory test (n-back) with three levels of difficulty at baseline and at a two-week follow-up. The intraclass correlation coefficients (ICC) values of the NASA-TLX ranged between 0.71 and 0.81, demonstrating good to excellent reliability. The mean ICA scores showed fair to good reliability, with ICCs ranging between 0.56 and 0.73. The mean ICA and NASA-TLX scores showed significant and moderate correlations (Pearson's r ranging between 0.30 and 0.33) with the third positive peak of the ERP at the midline channels. We conclude that ICA and NASA-TLX are reliable measures of cognitive workload in older adults. Further research is needed in dissecting the subjective and objective constructs of cognitive workload.

Reliability of P3 Event-Related Potential During Working Memory Across the Spectrum of Cognitive Aging.

Event-related potentials (ERPs) offer unparalleled temporal resolution in tracing distinct electrophysiological processes related to normal and pathological cognitive aging. The stability of ERPs in older individuals with a vast range of cognitive ability has not been established. In this test-retest reliability study, 39 older individuals (age 74.10 (5.4) years; 23 (59%) women; 15 non ß-amyloid elevated, 16 ß-amyloid elevated, 8 cognitively impaired) with scores on the Montreal Cognitive Assessment (MOCA) ranging between 3 and 30 completed a working memory (n-back) test with three levels of difficulty at baseline and 2-week follow-up. The main aim was to evaluate stability of the ERP on grand averaged task effects for both visits in the total sample (n = 39). Secondary aims were to evaluate the effect of age, group (non ß-amyloid elevated; ß-amyloid elevated, cognitively impaired), cognitive status (MOCA), and task difficulty on ERP reliability. P3 peak amplitude and latency were measured in predetermined channels. P3 peak amplitude at Fz, our main outcome variable, showed excellent reliability in 0-back (intraclass correlation coefficient (ICC), 95% confidence interval = 0.82 (0.67-0.90) and 1-back (ICC = 0.87 (0.76-0.93), however, only fair reliability in 2-back (ICC = 0.53 (0.09-0.75). Reliability of P3 peak latencies was substantially lower, with ICCs ranging between 0.17 for 2-back and 0.54 for 0-back. Generalized linear mixed models showed no confounding effect of age, group, or task difficulty on stability of P3 amplitude and latency of Fz. By contrast, MOCA scores tended to negatively correlate with P3 amplitude of Fz (p = 0.07). We conclude that P3 peak amplitude, and to lesser extent P3 peak latency, provide a stable measure of electrophysiological processes in older individuals.

Artificial neural networks in neurorehabilitation: A scoping review.

BACKGROUND: Advances in medical technology produce highly complex datasets in neurorehabilitation clinics and research laboratories. Artificial neural networks (ANNs) have been utilized to analyze big and complex datasets in various fields, but the use of ANNs in neurorehabilitation is limited. OBJECTIVE: To explore the current use of ANNs in neurorehabilitation. METHODS: PubMed, CINAHL, and Web of Science were used for the literature search. Studies in the scoping review (1) utilized ANNs, (2) examined populations with neurological conditions, and (3) focused on rehabilitation outcomes. The initial search identified 1,136 articles. A total of 19 articles were included. RESULTS: ANNs were used for prediction of functional outcomes and mortality (n = 11) and classification of motor symptoms and cognitive status (n = 8). Most ANN-based models outperformed regression or other machine learning models (n = 11) and showed accurate performance (n = 6; no comparison with other models) in predicting clinical outcomes and accurately classifying different neurological impairments. CONCLUSIONS: This scoping review provides encouraging evidence to use ANNs for clinical decision-making of complex datasets in neurorehabilitation. However, more research is needed to establish the clinical utility of ANNs in diagnosing, monitoring, and rehabilitation of individuals with neurological conditions.

The effects of cognitively demanding dual-task driving condition on elderly people's driving performance; Real driving monitoring.

BACKGROUND: Using in-vehicle audio technologies such as audio systems and voice messages is regarded as a common secondary task. Such tasks, known as the sources of non-visual distraction, affect the driving performance. Given the elderly drivers' cognitive limitations, driving can be even more challenging to drivers. The current study examined how listening to economic news, as a cognitively demanding secondary task, affects elderly subjects' driving performance and whether their comprehension accuracy is associated with these effects. METHODS: Participants of the study (N=22) drove in a real condition with and without listening to economic news. Measurements included driving performance (speed control, forward crash risk, and lateral lane position) and task performance (comprehension accuracy). RESULTS: The mean driving speed, duration of driving in unsafe zones and numbers of overtaking decreased significantly when drivers were engaged in the dual-task condition. Moreover, the cognitive secondary task led to a higher speed variability. Our results demonstrate that there was not a significant relationship between the lane changes and the activity of listening to economic news. However, a meaningful difference was observed between general comprehension and deep comprehension on the one hand and driving performance on the other. Another aspect of our study concerning the drivers' ages and their comprehension revealed a significant relationship between age above 75 and comprehension level. Drivers aging 75 and older showed a lower level of deep comprehension. CONCLUSION: Our study demonstrates that elderly drivers compensated driving performance with safety margin adoption while they were cognitively engaged. In this condition, however, maintaining speed proved more demanding for drivers aging 75 and older.