Japan-Multimodal Intervention Trial for the Prevention of Dementia: A randomized controlled trial.

INTRODUCTION: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI). METHODS: Participants aged 65-85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months. RESULTS: Of 531 participants, 406 completed the trial. The between-group difference in composite score changes was 0.047 (95% CI: -0.029 to 0.124). Secondary analyses indicated positive impacts of interventions on several secondary health outcomes. The interventions appeared to be particularly effective for individuals with high attendance during exercise sessions and those with the apolipoprotein E ε4 allele and elevated plasma glial fibrillary acidic protein levels. DISCUSSION: The multidomain intervention showed no efficacy in preventing cognitive decline. Further research on more efficient strategies and suitable target populations is required. HIGHLIGHTS: This trial evaluated the efficacy of multidomain intervention in individuals with MCI. The trial did not show a significant difference in preplanned cognitive outcomes. Interventions had positive effects on a wide range of secondary health outcomes. Those with adequate adherence or high risk of dementia benefited from interventions.

How patients with dementia influence caregiver burden using the Dementia Assessment Sheet for Community-based Integrated Care System-21 items (DASC-21) and Zarit Caregiver Burden Interview (ZBI).

BACKGROUND: Dementia is a disease that is frequently associated with significant caregiving burden. The present study was conducted on patients with dementia in order to investigate the causes of caregiver burden using the Dementia Assessment Sheet for Community-based Integrated Care System-21 items (DASC-21) and Zarit Caregiver Burden Interview (ZBI). METHODS: The study subjects consisted of 206 elderly patients (mean age: 80.9 ± 5.9 years) with dementia in an outpatient clinic. Current age, gender, type of dementia, Mini-Mental State Examination, Hasegawa Dementia Scale-Revised, Clinical Dementia Rating (CDR), Geriatric Depression Scale (GDS) and the DASC-21 were investigated. Caregiver burden was assessed by using the ZBI. Behavioural and Psychological Symptom of Dementia (BPSD) were evaluated by using the Neuropsychiatric Inventory (NPI). Simple regression analysis for the ZBI was performed with respective risk factors as independent variables. Thereafter, multiple regression analysis was performed. RESULTS: The mean ZBI score was 28.0 ± 18.1, whereas mean DASC-21 score was 44.4 ± 13.2. Simple regression analysis for the ZBI was performed with respective risk factors as independent variables. The DASC-21 (P < 0.001), CDR (P < 0.001), NPI (P < 0.001), and GDS (P = 0.034) were significantly associated with the ZBI. For each item of the DASC-21, Memory (P < 0.001), Orientation (P < 0.001), Solving issues/Common sense (P < 0.001), Instrumental activities of daily living (IADL) outside the home (P < 0.001), IADL inside the home (P < 0.001), Physical ADL① (P < 0.001) and Physical ADL② (P = 0.014) were also significantly associated with the ZBI. To find the independent association of the ZBI, multiple regression analysis was performed. The results showed that DASC-21 (P < 0.001) and NPI (P < 0.001) had significant correlation. For each item of the DASC-21, Memory (P = 0.014) and Solving issues/Common sense (P < 0.001) were also shown to have significant correlation. CONCLUSIONS: Both BPSD, cognition and IADL have affected caregiver burden. The DASC-21 is useful for determining the causes of caregiver burden of dementia patients.

Day service use and improved Serial 7 and Verbal fluency scores in patients with Alzheimer's disease.

BACKGROUND: Day services (DS) are provided as part of the Japanese public nursing care system. Recent studies have suggested a possible relationship between DS use and limited progression of Alzheimer's disease (AD). This study examined in detail the relationship between improvements in cognitive function and DS use in people with AD. METHODS: We retrospectively analysed Revised Hasegawa Dementia Scale (HDS-R) scores of 208 patients with AD at five memory clinics over a 6-month period. The patients were divided into a group that started using DS (n = 132) and a group that did not (n = 76) during the study period. We then compared each participant's total and item scores on the HDS-R between the first clinic visit and 6 months later also compared scores between DS users and non-users. RESULTS: DS non-users were younger, predominantly male, had longer school education, and better total HDS-R score at the first visit. After 6 months, DS users showed significantly improved total HDS-R score and individual Serial 7 and Verbal fluency scores. Immediate memory scores were comparable between the first visit and after 6 months. Among the DS users, more frequent participation in DS was significantly associated with improved total HDS-R score. CONCLUSIONS: DS use was significantly associated with improved HDS-R scores, especially for the Serial 7 and Verbal fluency tasks, and there was no deterioration in Immediate memory score. These results suggest the usefulness of DS participation as a non-pharmacological therapy.

Most families tend to realize progress of Alzheimer's disease when behavioural and psychological symptoms are obvious.

BACKGROUND: Alzheimer's disease (AD) is a common cognitive disease that can progress at an accelerating rate. Even with early diagnosis, the families might not recognize AD progressing unless behavioural and psychological symptoms of dementia (BPSD) develop. In many cases, discrepancies could exist between family-assessed AD stage and diagnosed AD stage. This study explored such discrepancies and potential clinical implications. METHODS: Participants were 161 new outpatients with AD or mild cognitive impairment at four memory clinics whose AD stage was diagnosed using the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental State Examination (MMSE). We classified patients into four groups according to AD severity. Family members completed the Functional Assessment Staging (FAST) scale during an interview. We then assigned patients to three groups according to discrepancies between family-assessed and diagnosed AD stage. Families also completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), which assesses 12 neuropsychiatric domains, in order to examine the presence of BPSD in relation to AD stage. RESULTS: Most families (74%-80%) assessed patients as having milder AD than the diagnosed stage. NPI-Q scores and duration of education significantly affected discrepancies with HDS-R and MMSE scores. The NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance significantly affected family-assessed FAST. Families of patients with more years of education assessed the AD stage as more advanced than the diagnosed stage. Surprisingly, living together did not significantly affect the discrepancy. CONCLUSIONS: Most families assessed AD as milder than the clinically diagnosed AD stage. In addition, high NPI-Q scores and more years of school education significantly affected the discrepancy. Family-assessed FAST was significantly affected by the NPI-Q domains of anxiety, apathy/indifference, aberrant motor behaviours, and appetite/eating disturbance. These results suggest that obvious BPSD are significant factors for Japanese families to recognize AD progress.

Clinical characteristics of participants enrolled in an early identification and healthcare management program for dementia based on cluster analysis and the effectiveness of associated support efforts.

OBJECTIVE: Although early identification and management services for dementia have become more widespread, their efficacy and the clinical characteristics of service have yet to be fully evaluated. Therefore, the objective of this study is to clarify these issues. MEASUREMENTS: The subjects were 164 Japanese users of an early identification and management program for dementia, known as the Initial-phase Intensive Support Team (IPIST), between 2013 and 2015. Nonhierarchical cluster analysis was used to derive subgroups based on cognitive status and ability in activities of daily living (ADL) and behavioral and psychological symptoms of dementia (BPSD). One-way analysis of variance was performed to evaluate differences among the groups derived by the cluster analysis. A paired t test was used to assess how the clinical status of the groups changed between baseline and follow-up. RESULTS: Four groups were identified by cluster analysis, i.e. a mild group, a moderate group, a BPSD group with moderate cognitive impairment and severe BPSD, and a severe group with severe cognitive impairment and severe BPSD. Although there were no significant improvements in cognitive impairment or ADL in any group, significant improvements were found in BPSD in the BPSD and severe BPSD groups. Caregiver burden was significantly lessened in all groups. Clinical diagnosis and long-term care insurance service utilization rates were significantly improved overall. CONCLUSION: The users of IPIST were classified into four subgroups based on their clinical characteristics. The IPIST program could improve the quality of life of people with dementia and their caregivers.

Use of day services improved cognitive function in patients with Alzheimer's disease.

AIM: Day services (DS) are part of the public nursing care system in Japan. The purpose of DS is to help elderly individuals maintain mental and physical functions, eliminate feelings of isolation among homebound users, and reduce the burden of care on family members. However, the relationship between DS and the progression of Alzheimer's disease (AD) remains unclear. METHODS: We retrospectively analyzed 161 AD patients based on available Mini-Mental State Examination (MMSE) scores. The patients were divided into two groups: those who started to use DS (n = 106) and those who did not use DS (n = 55). We then compared the groups' MMSE scores between the first memory clinic visit and the 6-month point. RESULTS: There were no significant differences between the two groups with regard to sex and the number of family members, but the non-DS group was younger, had more education, and had better MMSE scores at the first visit. At 6 months, we found a significant improvement in the MMSE scores of DS users, reflecting improved cognitive function. In addition, lower MMSE score at the first visit was associated with greater improvement in MMSE score at 6 months. Interestingly, the frequency of DS use had no significant effect on MMSE score. However, after approximately 6 months, DS use significantly improved the cognitive function of AD patients. CONCLUSIONS: DS use significantly improved the cognitive function of AD patients. However, most DS users in Japan are older and have severe dementia. Patients who are younger, have more education, or have mild dementia dislike using DS. As a significant difference was found in the MMSE scores between the two groups after 6 months, DS use appears to be a useful non-drug therapy.

Dementia Cafés as Hubs to Promote Community-Integrated Care for Dementia through Enhancement of the Competence of Citizen Volunteer Staff Using a New Assessment Tool.

INTRODUCTION: Dementia cafés have recently been attracting attention. The increased involvement of citizen volunteers and the competence of dementia café staff could enhance the potential of dementia cafés. The aim of the present study was to examine enhancement of the competence of citizen volunteers using a new assessment tool. METHODS: This cross-sectional analysis included 433 dementia café staff members, including medical and care professionals and citizen volunteers. A 20-item dementia café staff self-assessment (DCSA) instrument was newly developed. After confirmation of the reliability and validity of the instrument, DCSA scores among citizen volunteers were evaluated. RESULTS: DCSA showed very good psychometric properties. The mean (±SD) DCSA score was significantly higher for café staff with a medical and care professional background (n = 267) than for citizen volunteers (n = 166) (2.2±0.5 vs. 1.7±0.7, respectively; p < 0.001). The DCSA scores of citizen volunteers became significantly higher with increasing attendance (minimum: n = 24; 1.3±0.7; intermediate: n = 65; 1.6±0.6; and frequent: n = 77; 1.8±0.7; p < 0.01). CONCLUSION: Assessment of the competence of dementia café staff using the DCSA revealed the potential of citizen volunteers. This tool could also enhance the potential of dementia cafés.

Efficacy and safety of idalopirdine for Alzheimer's disease: a systematic review and meta-analysis.

OBJECTIVE: The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed. METHODS: We included RCTs of idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure. RESULTS: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) = -0.41, P = 0.32, I2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD = -2.15, P = 0.005, moderate AD subgroup: MD = -2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient, -0.0289), ADAS-cog at baseline (coefficient, -0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments. CONCLUSIONS: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.

Japanese Old Stories Cognitive Scale: a screening test to detect cognitive disease and prompt visiting a memory clinic.

BACKGROUND: Early detection and diagnosis is critical in enhancing treatment outcomes for those with cognitive disease. However, most Japanese patients are averse to visiting mental health clinics or taking cognitive screening examinations. A new simple screening test is needed that is acceptable to patients and encourages them to visit a memory clinic if indicated. METHODS: We developed a brief screening examination, consisting of four common Japanese old stories, for detection of cognitive disease. A total of 311 patients at three outpatient memory clinics completed the screening test, responding to a 10-question, fill-in-the-blanks assessment. Questions were read aloud to patients with visual impairment, and we transcribed the spoken responses of patients who were physically incapable of writing. The Hasegawa Dementia Scale-Revised (HDS-R) and Mini-Mental State Examination (MMSE) were administered at the same time. RESULTS: Using the developed Japanese Old Stories Cognitive Scale (JOSS), we found significant differences between dementia and control or mild cognitive impairment (MCI) groups. The JOSS was less affected by education level than the HDS-R or MMSE, possibly because Japanese old stories are usually learned from family members during preschool years. The JOSS may be able to detect remote memory disturbance in addition to other cognitive dysfunctions. CONCLUSIONS: Most patients with AD, even in advanced stages, are averse to visiting a memory clinic because it can be difficult to accept any resulting diagnosis of cognitive disease. JOSS is a quick and simple screening tool to gather evidence of cognitive dysfunction and prompt a referral to a memory clinic. Patients with cognitive disease found the JOSS acceptable, and its high specificity could be useful in encouraging patients to visit already-crowded memory clinics for formal diagnosis and intervention.

A comparative study: visual rating scores and the voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging among subjects with Alzheimer's disease, mild cognitive impairment, and normal cognition.

AIM: Hippocampal atrophy shown on magnetic resonance imaging can differentiate Alzheimer's disease (AD) patients from subjects with normal cognition (NC). Simplified automated methods that use volumetric analysis, such as as the voxel-based specific regional analysis system for AD, have become widely used in Japan. However, the diagnostic value of the voxel-based specific regional analysis system compared with visual rating scores for clinical diagnosis is unclear. METHODS: Study participants consisted of 37 AD patients, 29 mild cognitive impairment (MCI) patients, and 21 NC subjects. All participants underwent neuropsychological testing and magnetic resonance imaging. The imaging was scored visually for regional brain atrophy by two raters based on a newly developed visual rating score. The voxel-based specific regional analysis system for AD scores were calculated with the analysis system's advanced software. We analyzed whether these scores aid in discriminating among AD, MCI, and NC. RESULTS: The AD group had significantly different visual rating scores, regional analysis scores, and all neuropsychological test scores than the NC group. The AD group had significantly different visual rating scores than the MCI group, and a significant difference was observed between the MCI and NC groups on regional analysis scores. Both the visual rating and regional analysis scores showed equivalent correlations with the neuropsychological test scores. CONCLUSIONS: Both the visual rating and regional analysis scores are clinically useful tools for differentiating among AD, MCI, and NC.

A Dementia Café as a Bridgehead for Community-Inclusive Care: Qualitative Analysis of Observations by On-the-Job Training Participants in a Dementia Café.

BACKGROUND/AIMS: Dementia cafés are becoming widespread as a new approach to dementia care, but their operational procedures and significance have not been adequately studied. METHODS: On-the-job training (OJT) for professionals planning to operate a dementia café in the future was conducted in a pioneering dementia café in Japan. The reports of OJT trainees' observations and learning were analyzed qualitatively. RESULTS: Reports could be summarized in up to 9 themes: 2 related to the atmosphere and significance of the café, 3 related to the guests, such as people with dementia and their families, and 4 related to the café staff. DISCUSSION: The results of the present study identified the elements that make up dementia cafés and their significance and suggest that dementia cafés could be a new type of community resource for dementia care in the future.

Present status and road map to achieve inclusive and holistic care for dementia in a Japanese community: analysis using the Delphi method.

BACKGROUND/AIMS: Dementia is a priority issue in the public health realm. However, few reports address problems of dementia in the real world or provide comprehensive road maps to solve these problems. METHODS: Nine groups of questions covering 4 topics were discussed using the Delphi method, relating to (1) current achievements and challenges regarding inclusive and holistic care in the community, (2) patients who are at a high risk of being excluded from care, (3) suggestions for a road map for the establishment of better and more inclusive medical and social care, and (4) unmet needs of patients with dementia. RESULTS: In total, 477 opinions were obtained. Family issues, psychological/behavioral symptoms, and complications secondary to physical disorders are main factors for being excluded from care. To create a road map for care we have to address the topics of reaffirming care principles, multidisciplinary coalitions, and education for stakeholders. CONCLUSION: Further effective collaboration to promote dementia care is required.

Clinical characteristics of older patients with suspected or diagnosed dementia during hospitalization.

AIM: In Japan, an additional system for patients with suspected or diagnosed dementia during hospitalization for physical illness began in 2016. We examined the clinical characteristics of older patients with suspected or diagnosed dementia during hospitalization. METHODS: The study participants consisted of 569 patients. Current age, sex, comorbidities, causative disease for admission, body mass index (BMI), blood tests, environment before admission, prescription history before admission and rate of delirium were examined. Simple regression analysis for high-frequency diseases was carried out with the respective risk factors as independent variables. Multiple regression analysis was then carried out. RESULTS: Infection had the highest frequency in the causative diseases for admission. A total of 48% of patients had delirium during hospitalization. The delirium group had the highest frequency of being at home. In the infection group, BMI and serum albumin were lower in the non-infection group (BMI 19.0 ± 3.7 vs 20.4 ± 4.1; P < 0.001, albumin 2.1 ± 0.7 vs 3.3 ± 0.6 g/dL; P < 0.001 respectively). White blood cell count and C-reactive protein were higher than in the non-infection group, respectively (white blood cell count 11181.4 ± 6533.3 vs 8765.8 ± 111 424.3/µL; P = 0.007, C-reactive protein 8.6 ± 8.6 vs 3.0 ± 5.2 mg/dL; P < 0.001 respectively). Using independent factors associated with infection, multiple regression analysis was performed. BMI (P = 0.013), serum albumin (P < 0.001) and nursing home care before admission (P < 0.001) had significant correlations. CONCLUSIONS: Assessment of delirium and the environment before admission of older patients with suspected or diagnosed dementia when hospitalized are necessary. Furthermore, evaluation of nutrition might also contribute to reducing deterioration due to physical illness. Geriatr Gerontol Int 2024; 24: 641-645.

Characteristics of Changes in Caregiver Burden during Follow-up at a Memory Clinic: A Retrospective Cohort Study.

Background: Because dementia is a long-term condition, the appropriate involvement of health-care professionals is considered important. However, little is known about the factors associated with changes in family caregiver burden. Objective: To clarify changes in family caregiver burden and associated factors during follow-up at a memory clinic. Methods: A retrospective cohort study was conducted, enrolling 495 pairs of patients with dementia or mild cognitive impairment and their family caregivers. A total of 120 pairs completed the second evaluation. The caregiver burden was assessed using the Zarit Burden Interview (ZBI). Data at the initial visit and after an average follow-up of about 2 years were compared and analyzed. Results: At initial visit, the patients' mean age, Mini-Mental State Examination (MMSE) and ZBI scores were 78.6±5.6 years, 23.3±3.5, and 22.6±16.7, respectively. At follow-up, MMSE scores decreased (21.4±4.5, p < 0.001), but ZBI scores remained similar (22.5±13.6). When the difference in ZBI scores between the two time points was defined as ΔZBI, and the related factors were analyzed by multiple regression analysis, ZBI scores at the initial visit, start of psychotropic drug, and decrease of neuropsychiatric symptoms were identified as significant factors (p < 0.001, p = 0.003, p < 0.001, respectively). A significant negative correlation was found between ZBI scores at the initial visit and ΔZBI (r = -0.588, p < 0.001). Conclusions: These findings suggest the importance of assessing changes in the burden experienced by family caregivers during the disease follow-up.

Electroencephalography can Ubiquitously Delineate the Brain Dysfunction of Neurodegenerative Dementia by Both Visual and Automatic Analysis Methods: A Preliminary Study.

Introduction: The aim was to examine the differences in electroencephalography (EEG) findings by visual and automated quantitative analyses between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods: EEG data of 20 patients with AD and 24 with DLB/PDD (12 DLB and 12 PDD) were retrospectively analyzed. Based on the awake EEG, the posterior dominant rhythm frequency and proportion of patients who showed intermittent focal and diffuse slow waves (IDS) were visually and automatically compared between the AD and DLB/PDD groups. Results: On visual analysis, patients with DLB/PDD showed a lower PDR frequency than patients with AD. In patients with PDR <8 Hz and occipital slow waves or patients with PDR <8 Hz and IDS, DLB/PDD was highly suspected (PPV 100%) and AD was unlikely (PPV 0%). On automatic analysis, the findings of the PDR were similar to those on visual analysis. Comparisons between visual and automatic analysis showed an overlap in the focal slow wave commonly detected by both methods in 10 of 44 patients, and concordant presence or absence of IDS in 29 of 43 patients. With respect to PDR <8 Hz and the combination of PDR <8 Hz and IDS, PPV and NPV in DLB/PDD and AD were not different between visual and automatic analysis. Conclusions: As the noninvasive, widely available clinical tool of low expense, visual analysis of EEG findings provided highly sufficient information to delineate different brain dysfunction in AD and DLB/PDD, and automatic EEG analysis could support visual analysis especially about PD.

Health Care Resource Use and Social Costs in Mild Cognitive Impairment and Mild Alzheimer's Disease.

Background: As the number of patients with dementia increases, so do the social costs. In recent years, attempts have been made to reduce risk to be dementia and treat it from the early stages of the disease, making it important to estimate the costs of the early stages. Objective: To estimate the medical and social costs of the early stages of Alzheimer's disease (AD), which include mild cognitive impairment (MCI) due to AD and mild AD. Methods: Questionnaires were used to obtain basic information (e.g., age, cognitive function) and medical costs, social care costs, family caregiver medical costs, and family caregiver informal care costs from patients with MCI due to AD or mild AD who were attending a memory clinic. A comparison was then conducted between these two groups. Results: Patients with mild AD had higher total costs, patient medical costs, patient social care costs, and family caregiver informal care costs than did patients with MCI; however, only patient medical costs were significantly different (p = 0.022). A detailed analysis of patient medical costs revealed that anti-dementia drug treatment costs were significantly higher in patients with mild AD (p <  0.001). Conclusion: Compared with patients with mild AD, those with MCI may have lower patient and family caregiver costs. As it is important to reduce social costs through risk reduction and therapeutic interventions from the early stages of AD, the present findings could help estimate the social costs and verify the cost-effectiveness of early interventions for AD.

EFFECTS OF REHABILITATION PROGRAM FOCUSED ON IMPROVING REAL-LIFE DAILY ACTIVITIES OF PATIENTS WITH MILD COGNITIVE IMPAIRMENTS OR DEMENTIA AND THEIR CAREGIVERS.

Objective: To evaluate the effectiveness of a dyadic outpatient rehabilitation program focused on improving the real-life daily activities of patients with mild cognitive impairments or dementia and their caregivers. Design: Retrospective study. Subjects: Eight patients with mild cognitive impairments or dementia and their caregivers. Methods: The rehabilitation program comprised eight 1-hour sessions by occupational therapists with patients and his/her caregivers. Patients were assessed for motor function, cognitive function, and quality of life, and their caregivers were assessed for depression and caregiver burden. Participants were assessed at pre-program and post-program, and 3-month follow-up. Results: The scores of caregiver-assessed Quality of life in Alzheimer's disease scale in patients significantly improved at post-program (median [interquartile range], 30.0 [7.0]) compared with pre-program (27.0 [2.8], effect size = 0.77, p = 0.029). In caregivers, the Zarit Caregiver Burden Interview scores decreased significantly at post-program (16.5 [13.0]) compared with pre-program (22.0 [17.5], effect size = 0.72, p = 0.042). There were no significant differences in other assessments. Conclusions: The rehabilitation program focused on real daily activities and demonstrated to improve patients' quality of life and caregivers' depression and caring burden through patient-caregiver interaction. Future enhanced follow-up systems are warranted.