Ming Chyi Pai

Gait and balance analysis for patients with Alzheimer's disease using an inertial-sensor-based wearable instrument

Despite patients with Alzheimers disease (AD) were reported of revealing gait disorders and balance problems, there is still lack of objective quantitative measurement of gait patterns and balance capability of AD patients. Based on an inertial-sensor-based wearable device, this paper develops gait and balance analyzing algorithms to obtain quantitative measurements and explores the essential indicators from the measurements for AD diagnosis. The gait analyzing algorithm is composed of stride detection followed by gait cycle decomposition so that gait parameters are developed from the decomposed gait details. On the other hand, the balance is measured by the sway speed in anterior-posterior (AP) and medial-lateral (ML) directions of the projection path of bodys center of mass (COM). These devised gait and balance parameters were explored on twenty-one AD patients and fifty healthy controls (HCs). Special evaluation procedure including single-task and dual-task walking experiments for observing the cognitive function and attention is also devised for the comparison of AD and HC groups. Experimental results show that the wearable instrument with the designed gait and balance analyzing system is a promising tool for automatically analyzing gait information and balance ability, serving as assistant indicators for early diagnosis of AD.

Cognitive map in patients with mild Alzheimer's disease: A computer-generated arena study

OBJECTIVE In addition to memory impairment, a tendency to get lost is among the initial symptoms in patients with Alzheimer disease (AD). At least two kinds of wayfinding strategies, egocentric and allocentric, have been proposed. It is believed that people may form a cognitive map after repeated movement in a specific environment, and are able to use it as an aid to navigation. In the present study, we investigated the cognitive maps in early AD patients and their application in a computer-generated arena (CGA). METHODS We invited very mild AD (CDR 0.5) patients and normal controls (NCs) to participate in the current study. Hand-drawing tests were used to assess their supposedly previously formed cognitive maps of familiar environments, and CGA was used to measure their new environment learning as well as the application of the old map. RESULTS Nineteen patients (8 females, mean age 67.6 years old, education 9.7 years, and MMSE 24) and 18 NCs (10 females, mean age 66.4 years old, education 8.8 years, and MMSE 27) completed the study. In the hand-drawing map part, both groups did equally well. In the new environment learning, NCs did better than the AD group on the third of six trials. As for the old environment navigation experiment, the AD group spent more time than the NCs in finding the target, but showed no difference to NC regarding the path traveled in the target quadrant. CONCLUSION Early AD patients maintain their ability to use a cognitive map and keep pretty good allocentric representation of their familiar environments as well as NC do, but probably both groups do not routinely use their cognitive map to navigate in everyday life properly.

Gait analysis for patients with Alzheimer'S disease using a triaxial accelerometer

This paper presents an inertial-sensor-based wearable device and its associated stride detection algorithm to analyze gait information for patients with Alzheimers disease (AD). The wearable gait analysis device is composed of a triaxial accelerometer, a microcontroller, and an RF wireless transmission module. To validate the effectiveness of the proposed device and algorithm, nine AD patients and three healthy controls were recruited to participate a gait analysis experiment. They were asked to mount the device on their foot and walk along a straight line of 40 meters at normal speed. The stride detection algorithm, consisting of procedures of data collection, signal preprocessing, and stride detection, has been developed for acquiring gait feature information from acceleration signals. The advantages of this wearable gait analysis device include the following: 1) It can be used anywhere without any external device, and 2) the stride detection algorithm can acquire gait feature information from acceleration signals automatically and effectively. Experimental results show that the AD patients exhibited a significantly shorter mean stride length and slower mean gait speed than those of the healthy controls. No significant differences in mean stride frequency and mean cadence were observed in the two groups. The variability in the percentage of the stance phase of the AD patients was slightly greater than that of the healthy controls. Based on the above results and discussions with physicians, we conclude that the proposed wearable gait analysis device is a promising tool for automatically analyzing gait information which can serve as indicators for early diagnosis of AD.

Apolipoprotein C-III is an amyloid-β-binding protein and an early marker for Alzheimer's disease

It has been demonstrated that peripheral injection of anti-amyloid-β (Aβ) antibodies to patients with Alzheimers disease (AD) and AD transgenic mice facilitate Aβ clearance. We hypothesized that peripheral circulating Aβ-binding proteins also possess the ability to enhance Aβ clearance and the levels of circulating Aβ-binding proteins could serve as early AD biomarkers. Circulating Aβ-binding proteins were isolated from plasma and identified by LC-MS/MS. Their levels were compared among non-demented individuals without AD family history (ND), with AD family history (ND-FH), and patients with mild AD. The results showed that most of the identified Aβ-binding proteins were apolipoproteins, i.e., apoA-I, apoB-100, apoC-III, and apoE. Aβ bound preferentially to apoA-I-enriched HDL, followed by apoC-III- and apoE-enriched VLDL, and bound less favorably to apoB-100-enriched LDL. Levels of apoA-I were reduced in AD patients and could be used to discriminate AD from ND groups (AUC: 0.93); whereas levels of apoC-III were reduced in both ND-FH and AD groups and could be used to differentiate ND-FH from ND individuals (AUC: 0.81). Both the levels of apoA-1 and apoC-III positively correlated with CASI and MMSE scores. In conclusion, these results suggest that plasma apoA-I could be a sensitive AD biomarker and individuals with low plasma levels of apoC-III are at risk for AD.

Development of a Questionnaire on Everyday Navigational Ability to Assess Topographical Disorientation in Alzheimer's Disease

We developed a Questionnaire on Everyday Navigational Ability (QuENA) to detect topographical disorientation (TD) in patients with Alzheimer’s disease (PwAD). In the QuENA, 3 items were designed to assess landmark agnosia, 2 for egocentric disorientation, 3 for heading disorientation, and 2 for inattention. The PwAD and their caregivers rated QuENA according to which TD symptoms would occur. Regarding the construct validity, confirmatory factor analysis showed that the caregiver version of the QuENA fits the proposed TD model well but the patient version does not. Regarding the internal consistency, the Cronbach’s α for the caregiver version was 0.91 and that for the patient version was 0.87. A discrepancy existed between the appraisal of navigational abilities by PwAD and by caregivers, and it was correlated with the number of getting lost (GL) events. The caregiver version of QuENA is a feasible, reliable, and valid instrument to assess TD and it also discriminates well between the PwAD with GL and those without.

Montreal Cognitive Assessment and Mini-Mental State Examination performance in patients with mild-to-moderate dementia with Lewy bodies, Alzheimer's disease, and normal participants in Taiwan

BACKGROUND The aim of this study was to examine and test the sensitivity, specificity, and threshold scores of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) and determine those that best correspond to a clinical diagnosis of dementia with Lewy bodies (DLB). METHODS Sixty-seven Alzheimers disease (AD), 36 DLB, and 62 healthy participants without dementia (NC), aged 60 to 90, were enrolled. All three groups took the MoCA and MMSE tests at the same time. The Cochran-Mantel-Haenszel tests and receiver operating characteristics curve analysis were used to compare the different neuropsychological test results among the groups. RESULTS The cut-off point of the MoCA for AD was 21/22 with a sensitivity of 95.5% and a specificity of 82.3% (area under the curve (AUC): 0.945), and the cut-off point for DLB was 22/23 with a sensitivity of 91.7% and a specificity of 80.6% (AUC: 0.932). For the MMSE, the cut-off points for AD and for DLB from NC were all 24/25, with a sensitivity of 88.1% and a specificity of 85.5% for AD (AUC: 0.92), and a sensitivity of 77.8% and a specificity of 85.5% for DLB (AUC: 0.895). After controlling sex, age, and education, AD and DLB had lower scores in all MoCA subscales than the NC group (p < 0.05), except for the orientation and naming in DLB. In addition, AD had a lower score in the MoCA orientation (p = 0.03) and short-term memory (p = 0.02) than did DLB. CONCLUSIONS The MoCA is a more sensitive instrument than the MMSE to screen AD or DLB patients from non-dementia cases.

Impaired translation of spatial representation in young onset Alzheimer's disease patients

BACKGROUND Many early-stage Alzheimers disease (AD) patients suffer from spatial navigational impairment even in familiar environments. Growing evidence shows that the retrosplenial cortex (RSC) is more damaged in young-onset AD patients (YOAD, onset age before 65) than in late-onset AD (LOAD) in the early-stage of AD. Impaired translation between egocentric and allocentric representations of the environment, as a cause for spatial navigational impairment, usually occurs in people with lesions in the RSC. OBJECTIVE To test translational ability between spatial representations in early-stage YOAD and LOAD patients. METHODS Tests deemed sensitive to translation of spatial representations were used to evaluate 29 AD (14 YOAD, 15 LOAD) and 27 cognitively healthy controls (14 younger NC and 13 older NC). RESULTS Younger NC outperformed YOAD in the tests of translation of spatial representations in spite of their equal basic visuoperceptual abilities and distance estimation. No such difference existed between LOAD and older NC. CONCLUSION The translation of egocentric-allocentric representation ability, as a principal function of RSC, does not deteriorate equally in early-stage AD patients of different onset age. That early-stage YOAD show more deviations in translation of their spatial representation ability deserves our attention because it may endanger their daily activities.

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE−BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

Economic impact of dementia by disease severity: exploring the relationship between stage of dementia and cost of care in Taiwan

Objective Given the shortage of cost-of-illness studies in dementia outside of the Western population, the current study estimated the annual cost of dementia in Taiwan and assessed whether different categories of care costs vary by severity using multiple disease-severity measures. Methods This study included 231 dementia patient–caregiver dyads in a dementia clinic at a national university hospital in southern Taiwan. Three disease measures including cognitive, functional, and behavioral disturbances were obtained from patients based on medical history. A societal perspective was used to estimate the total costs of dementia according to three cost sub-categories. The association between dementia severity and cost of care was examined through bivariate and multivariate analyses. Results Total costs of care for moderate dementia patient were 1.4 times the costs for mild dementia and doubled from mild to severe dementia among our community-dwelling dementia sample. Multivariate analysis indicated that functional declines had a greater impact on all cost outcomes as compared to behavioral disturbance, which showed no impact on any costs. Informal care costs accounted for the greatest share in total cost of care for both mild (42%) and severe (43%) dementia patients. Conclusions Since the total costs of dementia increased with severity, providing care to delay disease progression, with a focus on maintaining patient physical function, may reduce the overall cost of dementia. The greater contribution of informal care to total costs as opposed to social care also suggests a need for more publicly-funded long-term care services to assist family caregivers of dementia patients in Taiwan.

The Incidence and Recurrence of Getting Lost in Community-Dwelling People with Alzheimer’s Disease: A Two and a Half-Year Follow-Up

Getting lost (GL) is a serious problem for people living with Alzheimer’s disease (PwAD), causing psychological distress in both PwAD and caregivers, and increasing the odds of being institutionalized. It is thus important to identify risk factors for the GL events in PwAD. Between April 2009 and March 2012, we invited 185 community-dwelling PwAD and their caregivers to participate in this study. At the baseline, 95 had experienced GL (Group B); the remaining 90 (Group A) had not. We focused on the incidence of GL events and the associated factors by way of demographic data, cognitive function assessed by the Cognitive Ability Screening Instrument (CASI), and spatial navigation abilities as assessed by the Questionnaire of Everyday Navigational Ability (QuENA). After a 2.5-year period, the incidence of GL in Group A was 33.3% and the recurrence of GL in Group B was 40%. Multiple logistic regression analysis revealed that the inattention item on the QuENA and orientation item on the CASI had independent effects on the GL incidence, while the absence of a safety range was associated with the risk of GL recurrence. During the 2.5 years, the PwAD with GL incidence deteriorated more in the mental manipulation item on the CASI than those without. We suggest that before the occurrence of GL, the caregivers of PwAD should refer to the results of cognitive assessment and navigation ability evaluation to enhance the orientation and attention of the PwAD. Once GL occurs, the caregivers must set a safety range to prevent GL recurrence, especially for younger people.