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.
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.
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).
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.
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.
To explore the current use of ANNs in neurorehabilitation.
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.
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.
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.
Although growing evidence links beta-amyloid (Aβ) 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 Aβ (Aβ+) 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 CNAβ+ and CNAβ-.
Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment MoCA score 26 ± 2) and 17 CNAβ- 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 Aβ 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.
The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Similarly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ 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 Aβ 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 CNAβ+ group.
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.
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 β-amyloid elevated, 16 β-amyloid elevated, 8 cognitively impaired) with scores on the Montreal Cognitive Assessment (MOCA) ranging between 3 and 30 completed a working memory (
-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 (
= 39). Secondary aims were to evaluate the effect of age, group (non β-amyloid elevated; β-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 (
= 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.
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 (
-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.
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.
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.
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.
PROSPERO CRD42020175016 .
Background
Emerging evidence from animal and human studies shows that beta‐amyloid (Aβ) may induce neuronal hyperexcitability in the early stage of Alzheimer’s disease (AD). Electroencephalography ...(EEG) offers unparalleled temporal resolution in tracing distinct neurophysiological processes even in preclinical AD. The aim of this pilot study was to determine the relationship of Aβ accumulation and event‐related potential (ERP) in cognitively normal older adults.
Method
Aβ accumulation was characterized with 18F Florbetapir positron emission tomography (PET) scans. Global Aβ burden was assessed by taking the mean standard uptake value ratios (SUVR) of 6 predefined regions: anterior cingulate, posterior cingulate, precuneus, inferior medial frontal, lateral temporal, and superior parietal cortex. All participants completed a working memory task with three levels of difficulty (0‐,1‐,2‐back). ERP P3 peak amplitude and latency were extracted from the task effect (non‐target minus target). We used Pearson r to calculate associations between mean SUVR and P3 ERP at the midline channels Fz and Cz. Since the working memory task induced frontal cortical activity, we also explored the relationship between SUVR in the inferior medial frontal cortex and the frontal channels Fz, F3, and F4.
Result
Twenty‐seven (age: 73.9 ± 5.5; MOCA: 27.37 ± 2.0) completed both PET and EEG scans. Mean SUVR ranged from 0.95 to 1.60 and correlated negatively with P3 latency of the 2‐back at Cz (r = ‐0.40; p = 0.04) and Fz (r = ‐0.58; p = 0.002). SUVR in the inferior medial frontal cortex correlated negatively with P3 peak latency of 1‐back at Fz (r = ‐0.42; p = 0.03) and F3 (r = ‐0.49; p = 0.009), and of 2‐back at Fz (‐0.54; p = 0.004) and F3 (r = ‐0.40; p = 0.045). No correlations were found between global Aβ burden and P3 peak amplitude.
Conclusion
The negative relationship between Aβ accumulation and P3 latency provides preliminary support for the neuronal hyperexcitability hypothesis in preclinical AD. However, these findings need to be confirmed in a longitudinal cohort study with larger sample size.
Background
The P3 event‐related potential (ERP) is typically reduced and delayed in patients with Alzheimer’s disease (AD). The hippocampus is a core regulator of the P3 ERP. The aim of this study ...was to investigate the relationship between hippocampal volume and P3 peak amplitude and latency in cognitively normal older adults with (Aβ+) and without elevated amyloid (Aβ‐).
Method
Aβ was assessed using a Florbetapir F‐18A positron emission tomography scan. No participants showed cognitive impairments based on performance on neuropsychological tests. Hippocampal volume was measured from T1‐weighted magnetic resonance imaging using Freesurfer. 256‐channel high‐definition electroencephalography (EEG) was used to record brain activity while completing a working memory (1‐back) test. The 1‐back test consisted of 120 non‐targets and 60 targets and lasted about 7 minutes. P3 amplitude and latency of the task effect (non‐target – target) was extracted using EEGlab software. Midline (Fz, Cz, Pz) and frontal (F3, F4) were identified a priori as channels of interest.
Result
We assessed 12 Aβ‐ participants (age 75.0 ± 6.4; MOCA 27.8 ±1.4; 6 (50%) women) and 11 Aβ+ participants (age 71.8 ± 5.6; MOCA 27.7 ± 2.0; 8 (72% women). Pearson r correlations for the total group (n = 23) demonstrated significant and positive correlations between both left and right hippocampal volume (L/R HV) and peak P3 amplitude at Fz (L HV, r = 0.55, p = 0.006); R HV, r = 0.52, p = 0.01), Cz (L HV, r = 0.55, p = 0.006; R HV, r = 0.53, p = 0.01), F3 (L HV, r = 0.50, p = 0.01; R HV, r = 0.44, p = 0.03), F4 (L HV, r = 0.57, p = 0.004; R HV, r = 0.55, p = 0.007), but not with Pz (L HV, r = 0.24, p = 0.26; R HV, r = 0.33, p = 0.12). Hippocampal volume did not correlate with any P3 peak latencies.
Conclusion
Our preliminary findings suggest a relationship between hippocampal volume and P3 peak amplitude in the frontocentral channels in cognitively normal older adults. Further research will reveal the putative mechanisms of neurophysiological changes in preclinical AD.
•EEG measures may serve to reflect driver state during autonomous driving.•Older adults with cognitive impairment may benefit from autonomous driving.•Older adults with cognitive impairment exhibit ...greater changes in frontal theta power during take-over events compared to neurotypical older adults.
Automated vehicle (AV) technology may potentially improve road safety, independence, and mobility in older drivers with cognitive impairment (CI). Physiological sensors will be useful to provide feedback of the driver state to the AV controller system. The aim of this study was to compare changes in cortical activity recorded using electro-encephalography (EEG) during conditional automation between older adults with normal cognition (NC) and CI.
Fourteen older adults (age 72.43 (6.00); 10 (71%) women; nine with NC and five with CI) completed two driving simulator scenarios. Scenario 1 included conditional automated driving with an emergency take-over request (TOR) at the end of the drive. Scenario 2 was identical but with an additional non-driving related task (NDRT). EEG was recorded in three driver tasks: resting; automation; and TOR. The interaction effect of driver task (resting state – automated driving – TOR) and cognitive status (CI – NC) on frontal theta power was calculated using linear mixed models.
A significant interaction effect of driver task*cognitive status on frontal theta power was found in the scenario without NDRT (F = 5.85; p = 0.001). Post-hoc effects showed that older adults with CI showed greater changes in frontal theta power from resting state to the TOR event (β = 16.44 ± 6.35; p = 0.01) and from automated driving to the TOR event (β = 17.91 ± 6.11; p = 0.006) compared to controls. No interaction effects were found on frontal theta power in the scenario with NDRT.
Our study provides proof-of-concept that older adults with CI show increased cortical activity while engaging with AV technology compared to neurotypical older adults.
Background
The third positive peak of the event‐related potential (ERP P3) is understood to reflect neural resource utilization during working memory. We previously showed lower P3 ERP amplitude of ...the task effect in older adults with preclinical Alzheimer’s disease (AD). The aim of this study was to compare changes from baseline to 1‐year follow‐up in P3 ERP between older adults with and without preclinical AD.
Method
Cognitively normal, beta‐amyloid positive (CNAβ+, n = 14) participants and beta‐amyloid negative (CNAβ‐, n = 15) controls completed a working memory task (n‐back) with three levels of difficulty (0, 1, 2) at baseline and 1‐year follow‐up. ERP P3 peak amplitude and latency of the task effect (non‐target minus target) were extracted from continuous electroencephalography recording. The frontal midline channel Fz was identified a priori as the main channel of interest. Aβ accumulation was characterized with 18F Florbetapir positron emission tomography scans. Independent t‐tests, Fisher’s Exact, or Mann‐Whitney U tests were employed to compare baseline characteristics between groups. Linear mixed models with random intercept were used to compare changes in P3 peak amplitude and latency. Group (CNAβ+ vs CNAβ‐), time (baseline, 1‐year), and n‐back (0, 1, 2) were entered as main effects. The main analysis of interest was the interaction between group and time.
Result
Baseline age, sex, MOCA scores, and n‐back accuracy and response times did not differ (p>0.11) between CNAβ+ and CNAβ‐ groups Table 1. Additionally, no longitudinal changes in MOCA scores or n‐back performance were observed between groups (p>0.41). A significant group by time interaction effect in P3 peak amplitude at Fz was found between CNAβ+ and CNAβ‐ participants (p = 0.049). The P3 peak amplitude increased by 48% in CNAβ+ participants, whereas only a 19% increase was observed in CNAβ‐ participants.
Conclusion
The ERP revealed significant changes over time in P3 amplitude for the CNAβ+ participants compared to the CNAβ‐ controls. The greater increase of CNAβ+ task effect amplitude likely represents a growing imbalance in task specific resource allocation. Further investigation of this phenomenon is warranted to evaluate neuronal activity of preclinical AD and the use of P3 ERP as a potential screening tool.
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