Prevalence of mild behavioural impairment domains: a meta-analysis.

BACKGROUND: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. METHODS: A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. RESULTS: Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. CONCLUSIONS: AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.

A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms.

Alzheimer's disease (AD) is the commonest cause of dementia, characterized by the clinical presentation of progressive anterograde episodic memory impairment. However, atypical presentation of patients is increasingly recognized. These atypical AD include logopenic aphasia, behavioural variant AD, posterior cortical atrophy, and corticobasal syndrome. These atypical AD are more common in patients with young onset AD before the age of 65 years old. Since medical needs (including the behavioural and psychological symptoms of dementia) of atypical AD patients could be different from typical AD patients, it is important for clinicians to be aware of these atypical forms of AD. In addition, disease modifying treatment may be available in the future. This review aims at providing an update on various important subtypes of atypical AD including behavioural and psychological symptoms.

Prevalence of mild behavioural impairment: a systematic review and meta-analysis.

AIM: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by emergent neuropsychiatric symptoms in later life. There has been no systematic review or meta-analysis on the prevalence of MBI. The main aim of the study is to calculate the pooled prevalence of MBI. METHODS: A search of the literature on MBI in mild cognitive impairment (MCI), cognitively normal (CN), and subjective cognitive impairment (SCI) and CN but at risk (CN-AR) subjects published between 1 January 2003 and 28 September 2020 was conducted. Meta-analysis using a random effects model was performed to determine the pooled estimate of the prevalence of MBI. Meta-regression was performed to identify factors contributing to the variance of prevalence rate. A systematic review was also performed to study the impact of MBI in cognitive outcomes and its correlation to the pathology and genetics of Alzheimer's disease. RESULTS: Eleven studies conducted among 15 689 subjects underwent meta-analysis, revealing the pooled prevalence of MBI to be 33.5% (95% confidence interval (CI): 22.6%-46.6%). Seven studies conducted among 1358 MCI subjects underwent meta-analysis, revealing the pooled prevalence to be 45.5% (95%CI: 36.1%-55.3%). Four studies conducted among 13 153 CN subjects underwent meta-analysis, revealing the pooled prevalence to be 17.0% (95%CI: 7.2%-34.9%). Five studies conducted among 1158 SCI or CN-AR subjects underwent meta-analysis, revealing the pooled prevalence to be 35.8% (95%CI: 21.4%-53.2%). A systematic review of 13 studies showed that MBI has a significant impact on cognitive deterioration and is associated with the pathology and genetics of Alzheimer's disease. CONCLUSIONS: In MCI, CN, and SCI and CN-AR subjects, MBI is common. Our finding is potentially useful in planning future clinical trials.

A video-supported nurse-led advance care planning on end-of-life decision-making among frail older patients: Protocol for a randomized controlled trial.

AIM: To examine the effect of a video-supported nurse-led advance care planning to frail geriatric patients on end-of-life decision-making outcomes in patients and their carers. DESIGN: This is a double-blinded randomized controlled trial with parallel arms. METHODS: The protocol was approved by the Institutional Review Board of the participating hospital on 1 August 2018. Frail elders and their carer if any are enrolled during hospitalization, and undergo randomization after discharged. The intervention group receives a 2-week video-supported nurse-led advance care planning programme (N = 149) while the control group receives a 2-week health education program at home (N = 149). Follow-up surveys via telephone at 1 and 6 months measure outcomes regarding end-of-life decision-making from both the patients and the carers. CONCLUSION: Advance care planning discussion is to understand patient's values, preferences and treatment for care on their anticipation of future deterioration. Treatment options for end-of-life care may not be well-received especially elders because in the discussion process, technical medical terms are presented in an abstract, hypothetical way that are hard to understand. The present study aims to evaluate the effect of a nurse-led advance care planning supplementing with a video showing end-of-life treatment options to promote end-of-life care decision-making among frail geriatric patients. IMPACT: The results will help identify effective elements of advance care planning and inform the development of an evidence?based structured advance care planning intervention in response to the need for quality end-of-life care. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012341.

Combined quantitative amyloid-ß PET and structural MRI features improve Alzheimer's Disease classification in random forest model - A multicenter study.

RATIONALE AND OBJECTIVES: Prior to clinical presentations of Alzheimer's Disease (AD), neuropathological changes, such as amyloid-ß and brain atrophy, have accumulated at the earlier stages of the disease. The combination of such biomarkers assessed by multiple modalities commonly improves the likelihood of AD etiology. We aimed to explore the discriminative ability of Aß PET features and whether combining Aß PET and structural MRI features can improve the classification performance of the machine learning model in older healthy control (OHC) and mild cognitive impairment (MCI) from AD. MATERIAL AND METHODS: We collected 94 AD patients, 82 MCI patients, and 85 OHC from three different cohorts. 17 global/regional Aß features in Centiloid, 122 regional volume, and 68 regional cortical thickness were extracted as imaging features. Single or combined modality features were used to train the random forest model on the testing set. The top 10 features were sorted based on the Gini index in each binary classification. RESULTS: The results showed that AUC scores were 0.81/0.86 and 0.69/0.68 using sMRI/Aß PET features on the testing set in differentiating OHC and MCI from AD. The performance was improved while combining two-modality features with an AUC of 0.89 and an AUC of 0.71 in two classifications. Compared to sMRI features, particular Aß PET features contributed more to differentiating AD from others. CONCLUSION: Our study demonstrated the discriminative ability of Aß PET features in differentiating AD from OHC and MCI. A combination of Aß PET and structural MRI features can improve the RF model performance.

Disrupted Structural White Matter Network in Alzheimer's Disease Continuum, Vascular Dementia, and Mixed Dementia: A Diffusion Tensor Imaging Study.

BACKGROUND: Dementia presents a significant burden to patients and healthcare systems worldwide. Early and accurate diagnosis, as well as differential diagnosis of various types of dementia, are crucial for timely intervention and management. However, there is currently a lack of clinical tools for accurately distinguishing between these types. OBJECTIVE: This study aimed to investigate the differences in the structural white matter (WM) network among different types of cognitive impairment/dementia using diffusion tensor imaging, and to explore the clinical relevance of the structural network. METHODS: A total of 21 normal control, 13 subjective cognitive decline (SCD), 40 mild cognitive impairment (MCI), 22 Alzheimer's disease (AD), 13 mixed dementia (MixD), and 17 vascular dementia (VaD) participants were recruited. Graph theory was utilized to construct the brain network. RESULTS: Our findings revealed a monotonic trend of disruption in the brain WM network (VaD > MixD > AD > MCI > SCD) in terms of decreased global efficiency, local efficiency, and average clustering coefficient, as well as increased characteristic path length. These network measurements were significantly associated with the clinical cognition index in each disease group separately. CONCLUSION: These findings suggest that structural WM network measurements can be utilized to differentiate between different types of cognitive impairment/dementia, and these measurements can provide valuable cognition-related information.

The Use of Diffusion Kurtosis Imaging for the Differential Diagnosis of Alzheimer's Disease Spectrum.

Structural and diffusion kurtosis imaging (DKI) can be used to assess hippocampal macrostructural and microstructural alterations respectively, in Alzheimer's disease (AD) spectrum, spanning from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and AD. In this study, we explored the diagnostic performance of structural imaging and DKI of the hippocampus in the AD spectrum. Eleven SCD, thirty-seven MCI, sixteen AD, and nineteen age- and sex-matched normal controls (NCs) were included. Bilateral hippocampal volume, mean diffusivity (MD), and mean kurtosis (MK) were obtained. We detected that in AD vs. NCs, the right hippocampal volume showed the most prominent AUC value (AUC = 0.977); in MCI vs. NCs, the right hippocampal MD was the most sensitive discriminator (AUC = 0.819); in SCD vs. NCs, the left hippocampal MK was the most sensitive biomarker (AUC = 0.775). These findings suggest that, in the predementia stage (SCD and MCI), hippocampal microstructural changes are predominant, and the best discriminators are microstructural measurements (left hippocampal MK for SCD and right hippocampal MD for MCI); while in the dementia stage (AD), hippocampal macrostructural alterations are superior, and the best indicator is the macrostructural index (right hippocampal volume).

Incremental diagnostic value of 18F-Fluetemetamol PET in differential diagnoses of Alzheimer's Disease-related neurodegenerative diseases from an unselected memory clinic cohort.

To evaluate the incremental diagnostic value of 18F-Flutemetamol PET following MRI measurements on an unselected prospective cohort collected from a memory clinic. A total of 84 participants was included in this study. A stepwise study design was performed including initial analysis (based on clinical assessments), interim analysis (revision of initial analysis post-MRI) and final analysis (revision of interim analysis post-18F-Flutemetamol PET). At each time of evaluation, every participant was categorized into SCD, MCI or dementia syndromal group and further into AD-related, non-AD related or non-specific type etiological subgroup. Post 18F-Flutemetamol PET, the significant changes were seen in the syndromal MCI group (57%, p < 0.001) involving the following etiological subgroups: AD-related MCI (57%, p < 0.01) and non-specific MCI (100%, p < 0.0001); and syndromal dementia group (61%, p < 0.0001) consisting of non-specific dementia subgroup (100%, p < 0.0001). In the binary regression model, amyloid status significantly influenced the diagnostic results of interim analysis (p < 0.01). 18F-Flutemetamol PET can have incremental value following MRI measurements, particularly reflected in the change of diagnosis of individuals with unclear etiology and AD-related-suspected patients due to the role in complementing AD-related pathological information.

The fractional amplitude of low-frequency fluctuations signals related to amyloid uptake in high-risk populations-A pilot fMRI study.

Background: Patients with type 2 diabetes mellitus (T2DM) and subjective cognitive decline (SCD) have a higher risk to develop Alzheimer's Disease (AD). Resting-state-functional magnetic resonance imaging (rs-fMRI) was used to document neurological involvement in the two groups from the aspect of brain dysfunction. Accumulation of amyloid-ß (Aß) starts decades ago before the onset of clinical symptoms and may already have been associated with brain function in high-risk populations. However, this study aims to compare the patterns of fractional amplitude of low-frequency fluctuations (fALFF) maps between cognitively normal high-risk groups (SCD and T2DM) and healthy elderly and evaluate the association between regional amyloid deposition and local fALFF signals in certain cortical regions. Materials and methods: A total of 18 T2DM, 11 SCD, and 18 healthy elderlies were included in this study. The differences in the fALFF maps were compared between HC and high-risk groups. Regional amyloid deposition and local fALFF signals were obtained and further correlated in two high-risk groups. Results: Compared to HC, the altered fALFF signals of regions were shown in SCD such as the left posterior cerebellum, left putamen, and cingulate gyrus. The T2DM group illustrated altered neural activity in the superior temporal gyrus, supplementary motor area, and precentral gyrus. The correlation between fALFF signals and amyloid deposition was negative in the left anterior cingulate cortex for both groups. In the T2DM group, a positive correlation was shown in the right occipital lobe and left mesial temporal lobe. Conclusion: The altered fALFF signals were demonstrated in high-risk groups compared to HC. Very early amyloid deposition in SCD and T2DM groups was observed to affect the neural activity mainly involved in the default mode network (DMN).

Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer's Disease and Other Dementias.

BACKGROUND: With the more widespread use of 18F-radioligand-based amyloid-ß (Aß) PET-CT imaging, we evaluated Aß binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. OBJECTIVE: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer's disease (AD), and 2) MCI from other non-AD dementias (OD). METHODS: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). RESULTS: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aß binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. CONCLUSION: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

Association between functional status and ocular surface disease among local elderly population in Hong Kong.

Purpose: To evaluate the correlation between ocular surface disease (OSD) and functional status among elderly population over 60 years old in Hong Kong.Methods: Chinese subjects above 60 years old were recruited from the Ophthalmology clinic in Hong Kong West Cluster. Subjects demographic and questionnaires to evaluate the functional status were used to correlate with OSD objectively with clinical examination to assess the meibomian gland dysfunction (MGD), corneal staining, Schirmer's test and tear break-up time (TBUT); and subjectively with ocular surface disease index (OSDI).Results: Twenty-eight patients were recruited, with a mean age of 71.5 ± 6.8 years. There was good correlation between the findings of the two eyes for bilateral measurements. Corneal staining was present in 75% of the subjects, while 92.9% of them had positive MGD grading. TBUT was reduced in 85.7% of the subjects. There is a negative association between MGD grading and Barthel index (r = -0.55, p< .01), indicating worse activities of daily living is related to worse MGD. OSDI is negatively associated with Schirmer's test (r = -0.49, p< .01). A negative correlation is also found between TBUT value and corneal staining (r = -0.58, p< .01).Conclusions: There is a high prevalence of OSD among our subjects. Lower Barthel index (indicating worse Lawton's instrumental activities of daily living) is associated with worse MGD grading. In elderly with poor functional status, care should be taken to manage their OSD.

Chinese patients with Lewy body dementia had shorter survival and developed complications earlier than those with Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) and Lewy body dementia (LBD) are two common forms of dementia. There are still controversies regarding whether LBD patients have a worse clinical course than AD patients. METHODS: We retrospectively reviewed all biomarkers that supported AD and LBD patients presenting to the Memory Clinic of Queen Mary Hospital, Hong Kong, between 1 January 2008 and 30 December 2016. Diagnoses of AD and LBD were supported by clinical diagnostic criteria and biomarkers. LBD patients included those with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Baseline demographics, presenting clinical features, degree of cognitive impairment and specified clinical outcomes were compared. RESULTS: We recruited 31 AD and 25 LBD patients (18 DLB, 7 PDD). When measured from disease onset, LBD patients were noted to have shorter overall survival (p = 0.02) with earlier occurrence of falls (p < 0.001), dysphagia (p < 0.001), pneumonia (p = 0.01), pressure injuries (p = 0.003) and institutionalisation (p = 0.03) than AD patients. Cox regression analyses showed that LBD predicted falls (hazard ratio [HR] 5.86, 95% confidence interval [CI] 2.29-15.01, p < 0.001), dysphagia (HR 10.06, 95% CI 2.50-40.44, p = 0.001), pressure injuries (HR 17.39, 95% CI 1.51-200.10, p = 0.02), institutionalisation (HR 2.72, 95% CI 1.12-6.60, p = 0.03) and death (HR 2.96, 95% CI 1.18-7.42, p = 0.02). CONCLUSION: LBD patients had shorter overall survival with earlier occurrence of pre-specified long-term events compared with AD patients. LBD also independently predicted pre-specified long-term events.

Factors Associated with Poor Eye Drop Administration Technique and the Role of Patient Education among Hong Kong Elderly Population.

OBJECTIVES: To identify the risk factors for poor eye drop application technique in treatment-naïve subjects and to assess if patient education can benefit these subjects. METHODS: Chinese subjects above 60 years were recruited. Questionnaires, including Barthel index; Lawton's instrumental activities of daily living (ADL); Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale; and Montreal Cognitive Assessment (MoCA), were used to correlate with eye drop application technique (before and after patient education) using Spearman correlation analysis. A multiple linear regression was conducted to determine the predictors of successful administration technique and the improvement of technique after education. RESULTS: The data from 26 subjects (mean age 72) were analyzed. Eye drop instillation technique score improved from 5.42 at baseline to 7.33 after clear instructions. FRAIL score was an independent predictor of baseline score (p=0.003), as well as the improvement after patient education (p=0.012). Age, sex, education level, visual acuity, Barthel index, MoCA, and ADL score were not correlated with eye drop instillation technique, before nor after patient education. DISCUSSION: In patients with poor functional status as reflected by FRAIL score, eye drop application is prone to be ineffective. Education with step-by-step instructions could effectively improve the success of eye drop application.

Novel presenilin 1 mutation (p.F386I) in a Chinese family with early-onset Alzheimer's disease.

Autosomal dominant familial Alzheimer's disease accounts for 0.5% of all Alzheimer's disease. A familial Alzheimer's disease Chinese family, with 7 affected family members, underwent PSEN1 screening in 3 affected family members. A heterozygous novel missense mutation in the PSEN1 gene c.1156T>A, altering phenylalanine to isoleucine at codon 386, was identified. Because the change occurred in conserved domains of this gene and cosegregated with affected family members, this change may have a mutagenic and probably pathogenic effect.

Gender differences in rehabilitation outcomes among older Chinese patients.

Although gender differences have been demonstrated in cardiac and stroke rehabilitation, it remains unclear whether there are gender differences in geriatric rehabilitation. The purpose of this study is to investigate the relationship between gender and rehabilitation outcomes. We studied 1795 patients in two convalescence hospitals in Hong Kong. We defined absolute functional and motor gains as Barthel Index (BI) efficacy and Elderly Mobility Scale (EMS) efficacy while BI and EMS efficiency were efficacy divided by the length of stay. Satisfactory motor and functional outcomes were defined as discharge EMS ≥ 15 and BI ≥ 75. Compared with men, women had higher BI but lower EMS on admission and discharge. EMS and BI efficacy and efficiency were similar in both sexes. Female gender was a significant negative predictor for satisfactory motor outcome (p=0.0002) but a positive predictor for functional outcome (p=0.0007). Other predictors for satisfactory motor outcome were: age (p<0.001); urinary incontinence (p=0.0049); living at home (p=0.0056); admission EMS (p<0.001); admission BI (p=0.044). Other predictors for satisfactory functional outcome were: age (p=0.009); infection other than chest (p=0.047); urinary incontinence (p<0.001); Mini Mental State Examination (MMSE) (p=0.0004); admission EMS (p=0.005); BI (p<0.001). Women achieved a better functional outcome but a poorer motor outcome on discharge. Female gender was a positive predictor for functional outcome but a negative factor for motor outcome.

Relationship between admission albumin levels and rehabilitation outcomes in older patients.

The relationship between serum albumin level and rehabilitation outcome in older patients has not been fully explored. This study investigated this association in older Chinese patients. We studied 1604 patients in two geriatric convalescence hospitals. Admission albumin levels (g/l) were measured and segregated into three groups: <30 g/l; 30 to <35 g/l; ≥35 g/l. Absolute functional and motor gain were determined by Barthel index (BI) and elderly mobility scale (EMS) and expressed as BI efficacy and EMS efficacy. BI and EMS efficiency were deduced by the efficacy divided by the length of hospital stay (LOS). Satisfactory motor and functional outcomes were defined as discharge EMS≥15 and BI≥75. Significant improvement in EMS and BI scores across all 3 albumin groups on discharge was observed, with lower scores in low albumin groups. The EMS and BI efficacy were the same in 3 albumin groups. However, EMS and BI efficiency were higher in the high albumin groups. Admission albumin was not independent predictors for satisfactory motor and functional outcomes. For satisfactory motor outcome (EMS≥15), female gender (p=0.0004), age (p=0.0009) and urinary incontinence (p=0.0076) were negative predictors while living at home (p=0.0028), admission EMS (p<0.001) and BI score (p=0.0004) were positive predictors. For satisfactory functional outcome (BI≥75), age (p=0.015) and urinary incontinence (p<0.001) were negative predictors while female gender (p=0.0024), LOS (p=0.033), C-MMSE (p<0.001), admission EMS (p=0.003) and BI (p<0.001) were positive predictors. Admission albumin levels were related to functional and motor efficiency, but not with absolute functional and motor gain. Albumin was not an independent predictor for satisfactory motor and functional outcome.

Factors affecting institutionalization in older Hong Kong Chinese patients after recovery from acute medical illnesses.

Older patients with medical illnesses are at risk of institutionalization. The purpose of this study is to investigate the factors leading to institutionalization in older patients after recovery from medical illnesses. We studied 535 older patients in two convalescence hospitals in Hong Kong. Of them, 116 patients (21.7%) needed to move to nursing homes upon discharge. Univariate analysis showed that age, single/divorced/widowed status, longer length of stay, pressure sores, urinary incontinence, urinary catheterization, falls, dementia, diabetes mellitus, Barthel index (100), Elderly Mobility Score (EMS), Chinese version of the mini-mental state examination (C-MMSE) and albumin levels were significant factors associated with institutionalization. Multivariate analysis showed that being single/divorced/widowed (odds ratio=OR=2.74, 95% confidence interval=CI=1.36-5.53, p=0.0048), having urinary incontinence on discharge (OR=5.13, CI=2.66-10.6, p<0.001) and admission due to falls (OR=2.4, CI=1.03-5.57, p=0.04) were independent risk factors for nursing home admission. Higher admission EMS (OR=0.91, CI=0.84-0.97, p=0.009), admission C-MMSE (OR=0.93, CI=0.87-0.98, p=0.019), and discharge albumin levels (OR=0.93, CI=0.88-0.99, p=0.02) were independent protecting factors against nursing home admission. Knowledge of these factors can allow us to predict accommodation outcome and develop intervention strategy to reduce institutionalization in the older patients.

Zopiclone withdrawal: an unusual cause of delirium in the elderly.

We report a case of an elderly lady who was admitted for congestive heart failure. She developed delirium during the course of her hospital stay. Multiple investigations were performed but were unremarkable. Finally, a diagnosis of abrupt zopiclone withdrawal causing delirium was made. Zopiclone was resumed at a lower dose and delirium resolved completely.