Quality of life is an essential outcome parameter in geriatric research; however, research to date offers mixed evidence about the factors associated with health-related quality of life (HRQOL) among people with dementia (PWDs). We aimed to identify factors relating to HRQOL among PWDs living in long-term care (LTC) facilities.

A total of 299 from 1,607 registered long-term care facilities were randomly selected in every administrative region of Taiwan. A cross-sectional two-phase survey, which included the demographic data, comorbidities, EuroQol-5 dimensions-5 levels (EQ-5D-5L), mini-mental state examination (MMSE) score, clinical dementia rating scores (CDR), behavioral and psychological symptoms of dementia, and activities of daily living (ADL) of PWDs, was then conducted from 2019 to 2020.

A total of 1,313 PWDs who self-completed EQ-5D-5L were enrolled in this analysis with a mean age of 76.43 ± 12.7 years. The mean utility and visual analogue scale (VAS) scores of EQ-5D-5L were 0.10 (standard deviation, SD = 0.48) and 66.57 (SD = 20.67), respectively. Multivariate linear regression analysis showed that higher scores in ADL, instrumental ADL, and lower CDR sum scores were associated with higher EQ-5D-5L utility scores. Higher ADL scores and higher MMSE scores were associated with higher scores in an EQ-5D-5L-VAS. More depressive symptoms were related to both lower utility score and lower EQ-5D-5L-VAS score.

Findings highlight the importance to recognize and to treat depression to maintain HRQOL of PWDs in LTC facilities. Longitudinal studies are needed to better understand the long-term changes in HRQOL of PWDs.

tDCS application to the DLPFC is associated with the improvements of executive function, memory enhancement, language, processing speed, global cognitive symptoms and apathy over time after treatment. DLB is the second most common form of degenerative dementia. There is no FDA-approved medications that can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation(LTP), and influence memory and learning. tDCS has been proposed to affect long-term synaptic plasticity through LTP and long-term depression, thereby improving cognitive ability. So far, only two studies have evaluated the effect of tDCS in DLB. In this pilot study, we investigate the effect of tDCS on left DLPFC in DLB.

Fourteen DLB aged 55-90 years (mean age 76.4, with 4 males and 10 females) were included in a double-blind, randomized, sham-controlled cross over design study. DLB diagnostics is according to DSM-5 criteria. CDR ratings for DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process consists of daily sessions of active tDCS (or sham) for 10 consecutive days. The anodal electrode was placed over the left DLPFC and the cathodal electrode was placed over the right supraorbital area, with a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in a session. Before and after these treatment sessions, all subjects received a series of neuropsychological tests, including CDR, MMSE, CASI, NPI and WCST. Chi-square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess differences in participant demographic characteristics and to compare differences among groups.

The active tDCS group showed significant improvements on the three items of CASI, ‘language ability’, ‘concentration and calculation’, ‘categorical verbal fluency’, after active stimulations. There is no improvement in MMSE, CASI, NPI and WCST scores in the sham groups.

These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, may have some cognitive benefits in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Key words: Transcranial Direct Current Stimulation, Dementia with Lewy Bodies, cognitive function, Wisconsin Card Sorting Test, left DLPFC

Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. In pathology, the amyloid deposits in AD disrupts the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. An increasing number of studies have been concluded a positive therapeutic effect on cognition in AD. In brain stimulation, dorsolateral prefrontal cortex (DLPFC) was associated with improvements in memory enhancement, language, processing speed, global cognitive symptoms, and apathy over a period of treatment. Theoretically, the aftereffect of tDCS would need to be re-stimulated by tDCS to maintain its delayed plastic response benefits. In this pilot study, we investigate the maintenance effects of continuing tDCS at three different times, weekly, every two weeks, and every four weeks, for 12 weeks.

Twenty-eight AD participants aged 55-90 years were enrolled (mean age 72.7, 77.3, and 76.2 in the three groups - maintained weekly (7 cases), biweekly (9 cases) and every 4 weeks (12 cases)). The anodal electrode was placed over the left dorsal lateral prefrontal cortex and the cathodal electrode was placed over the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at (1) baseline, (2) post-10sessions of tDCS (in 2weeks), and (3) post-maintenance phase (total of 12 weeks). Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess differences in participant demographic characteristics and to compare differences in test scores between groups.

After 10 sessions of tDCS stimulations, the total CASI scores in the 1-week group improved significantly from baseline to 2 weeks. However, there are no significant difference in MMSE, CASI or WCST between baseline and after maintain phase stimulations in each group.

Although tDCS has a positive effect in AD, it is recommended to prolong the number of tDCS stimulations, such as 20 sessions in 4 weeks.

There is growing evidence that gray matter atrophy is constrained by normal brain network (or connectome) architecture in neuropsychiatric disorders. However, whether this finding holds true in individuals with depression remains unknown. In this study, we aimed to investigate the association between gray matter atrophy and normal connectome architecture at individual level in depression.

In this study, 297 patients with depression and 256 healthy controls (HCs) from two independent Chinese dataset were included: a discovery dataset (105 never-treated first-episode patients and matched 130 HCs) and a replication dataset (106 patients and matched 126 HCs). For each patient, individualized regional atrophy was assessed using normative model and brain regions whose structural connectome profiles in HCs most resembled the atrophy patterns were identified as putative epicenters using a backfoward stepwise regression analysis.

In general, the structural connectome architecture of the identified disease epicenters significantly explained 44% (±16%) variance of gray matter atrophy. While patients with depression demonstrated tremendous interindividual variations in the number and distribution of disease epicenters, several disease epicenters with higher participation coefficient than randomly selected regions, including the hippocampus, thalamus, and medial frontal gyrus were significantly shared by depression. Other brain regions with strong structural connections to the disease epicenters exhibited greater vulnerability. In addition, the association between connectome and gray matter atrophy uncovered two distinct subgroups with different ages of onset.

These results suggest that gray matter atrophy is constrained by structural brain connectome and elucidate the possible pathological progression in depression.

To explore and develop effective treatments is crucial for patients with Alzheimer’s dementia (AD). In pathology, the amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Although an increasing number of studies have been concluded a positive therapeutic effect on cognition in AD, tDCS studies to date are limited on exploring the duration of its efficacy. In this pilot study, we investigate the effects of tDCS in AD and verify its extending beneficial effects for 3 months follow-up period after the end of stimulation.

34 AD participants aged 55-90 years (mean age 75.9 (66-86)) were included in a double-blind, randomized, sham-controlled crossover study. All participants were randomly assigned to receive 10 consecutive daily sessions of active tDCS (or sham) and switched groups 3 months later. The anodal electrode was on the left dorsal lateral prefrontal cortex and the cathodal electrode was on the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at baseline and in 2 weeks, 4 weeks, and 12 weeks post-tDCS (or sham) 10 sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences of test scores between groups.

The active tDCS group showed significant improvements on CASI total scores from baseline to 2-weeks, 1-month and 3-months after active stimulations, though the improvement declined over time. There are also different presentations in total correct items, conceptual level responses, failure to maintain sets of WCST between active tDCS and sham groups. There is no difference in MMSE, CASI and WCST scores in the sham groups.

These results suggest a long term-beneficial effects of tDCS in AD.

The Brain Health Test-7 (BHT-7) is a revised tool from the original BHT, containing more tests about frontal lobe function. It was developed with theaim of identifying patients with mild cognitive impairment (MCI) and early dementia.

Here we report the validity of the BHT-7 versus the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in differentpsychiatry or neurology clinics.

Patients with memory complaints were recruited in this study from the outpatient clinic of psychiatry or neurology in 3 different kinds of hospitals. Allpatients underwent the evaluation of the BHT-7, MMSE, MoCA, and clinical dementia rating (CDR). The clinical diagnosis (normal, MCI, dementia) was made by consensus meeting, taking into account all available data.

Demographic data and the scores of the MMSE, MoCA, and BHT-7 between groups were compared. Logistic regression was adopted for analysis of optimal cutoff values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curve,and the area under the ROC curve (AUC).

We enrolled a total of 1090 subjects (normal 402, MCI 317, dementia 371); of them, 705 (64.7%) were female. There was a statistically significant differencein age, years of education, and 3 cognitive test scores among the 3 groups.

Compared with the MMSE and MoCA, the BHT-7 performed slightly betterthan MMSE and MoCA in differentiating MCI or dementia from the normalcontrols (Table 1). For BHT- 7, the cutoff point was 17 between normal andMCI, and 14 between normal and dementia. These cutoff points for BHT-7were consistent through 3 different clinical settings, but inconsistent for MMSE and MoCA. The testing time for the BHT-7 was about 5-7 minutes, shorter than that of the MMSE and MoCA.

Compared with MMSE and MoCA, the BHT-7 showed slightly better performance in differentiating normal from MCI or dementia subjects. The testing time for the BHT-7 was shorter, and its cutoff points were consistent through different outpatient clinic settings. The results support that BHT-7 is auseful cognitive screening tool for MCI or early dementia in various hospital settings.

Table 1

Comparisons of the performance of BHT-7, MMSE, MoCA

Dementia with Lewy Bodies (DLB), this second most common form of degenerative dementia, presents more functional disability, more potentially fatal complication, more impaired quality of life than Alzheimer’s dementia. There is no FDA-proved medication can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation, and influence memory and learning. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. So far, only two researches assess the effect of tDCS in DLB. In this pilot study, we investigate the effects of tDCS in DLB.

Using a double-blind, randomized, sham- controlled and crossover trial design, 11 DLB aged 55-90 years (mean age 77.8) were included in the study. DLB diagnostics is according to DSM-5 criteria. The CDR ratings of DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process includes consecutive daily sessions of active tDCS (or sham) for 10 days. The anodal electrode was over the left dorsal lateral prefrontal cortex (DLPFC) and the cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI, NPI and WCST, before and after these treatment sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences among groups.

On CASI, MMSE, NPI and WCST, there were no statistically significant differences between pre- and post the 10-session course for the active and the sham groups. No side effects reported during or immediately after active tDCS stimulation.

These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, do not improve cognition, behavioral and psychological symptoms in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.

We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.

MDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.

Late-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.

The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration.

A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012–2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1–364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve.

The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60–0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury.

Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

Identifying effective treatments is a critical issue for Alzheimer’s dementia (AD). The pathological amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Brain stimulation in dementia research, especially with relatively safe tDCS, has been taken seriously recently. In theory, tDCS affects long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Recently, an increasing number of studies have been conducted to evaluate the efficacy of tDCS in AD and concluded a positive therapeutic effect. Currently, there are no studies of tDCS for AD in Taiwan. In this study, we investigate the effects of tDCS in AD.

Using a double-blind, randomized and sham- controlled trial design, Sixteen AD aged 55-90 years (8 active, mean age 73.88 and 8 sham, mean age 74.75) were included in the study. AD diagnostics is according to DSM-5 criteria. The CDR ratings of AD participants ranged from 0.5 to 2. All subjects completed ten consecutive daily sessions in which they received either an active or a sham tDCS over the left dorsal lateral prefrontal cortex (anodal) and a cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 35 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI and WCST, before and after these treatment sessions on the first day and 4 weeks later. Chi- square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess the differences in participant demographic characteristics and to compare the differences among groups.

The active group showed significant improvement in total correct item, Conceptual level Responses (reflecting insight into the correct sorting principles), Categories Completed (reflecting overall success), and Trials to complete first categories (reflecting initial conceptual ability) of WCST 4 weeks later after the final stimulation. There were no statistically significant differences between before and after the 10-session course for the sham group.

tDCS stimulation improves cognitive operation and Conceptual Ability of AD.

To evaluate the effects of disease severity, corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (SARS) patients, both during acute and convalescent phases.

Self-administered mail questionnaires survey to 308 SARS patients after discharging from hospital. Both patients and their families were asked about symptoms related to various neuropsychiatric domains, and the questions covered both acute and convalescent phases.

Among the 102 (33%) valid replies, 65% had strong symptoms in convalescent phase as indicated by GHQ28 score ≥ 5. In multiple linear regression analysis, use of pulse steroid and total dosages of pulse steroid during hospitalisation were predictive for anxiety-depression, psychosis and behavioural symptoms in acute phase, the effects persisted in convalescent phase. Disease severity had direct correlation with symptoms in all neuropsychiatric domains at acute phase and anxiety-depression and cognition at convalescent phase. Health care workers had more neuropsychiatric complaints in both phases. Severity of symptoms, corticosteroids and social factors explained about half of the variances (R2 = 52) in anxiety-depression at acute phase and 33% at convalescent phase.

Severe disease, high dose corticosteroids and being health care workers were independent predictors of neuropsychiatric complaints in both acute and convalescent phases.