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.

Different glycaemia-related risk factors for incident Alzheimer's disease in men and women with type 2 diabetes-A sex-specific analysis of the Hong Kong diabetes database.

AIMS: Sexual dimorphism has been reported in the epidemiology, neurobiologic susceptibility and clinical presentation of Alzheimer's disease (AD). As poor glycaemic control is associated with increased risks of AD, we aimed to investigate whether glycaemia-related risk factors also differ between men and women, using a retrospective, sex-specific analysis of a large Chinese cohort with diabetes. MATERIALS & METHODS: A total of 85,514 Chinese individuals with type 2 diabetes (T2D; 46,783 women and 38,731 men), aged ≥60 years, were identified from electronic health records and observed for incident AD. Multivariable Cox regression analysis was used to evaluate the associations with incident AD of several glycaemia-related risk factors, including severe hypoglycaemia, mean HbA1c and indices of HbA1c variability, in men and women separately. RESULTS: Over a median follow-up of 6 years, women had a higher incidence of AD than men (2.3% vs. 1.2%, p < 0.001). Both men and women shared the same independent non-glycaemic clinical predictors, which included older age, lower body mass index and longer duration of diabetes. However, for glycaemia-related risk factors, we observed that severe hypoglycaemia and indices of HbA1c variability were independent predictors of incident AD in women but not in men, and the associations were irrespective of their baseline glycaemic control and duration of diabetes. CONCLUSIONS: Our findings highlighted that glycaemia-related risk factors for incident AD differ between men and women with T2D. Strategies to maintain glycaemic stability and avoid severe hypoglycaemia might be especially important to preserve healthy cognition in older women with diabetes.

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.

Prevalence of cognitive impairment among peritoneal dialysis patients: a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment (CI) is common among patients on peritoneal dialysis (PD), but it is under-recognized and systematic review on its prevalence and impact across different geographical locations or patient characteristics is lacking. METHODS: A search of the literature on CI in PD patients published between 1 Jan 1980 and 25.April 2019 was conducted. Meta-analysis using a random effects model was performed to determine the pooled estimate of the prevalence of CI. Meta-regression was performed to identify factors contributing to the variance of prevalence rate. A systematic review was also performed to study risk factors of CI and its impact on clinical outcomes. RESULTS: Eight studies were included and the relevant data from 1736 patients were extracted for analysis. Meta-analysis revealed a pooled prevalence of CI at 28.7% (95% CI 15.9-46%). Meta-regression analyses showed that the prevalence of CI was unrelated to patient's age, gender, duration of PD, healthcare policy of dialysis modality, the prospective or retrospective nature of studies, or year of publication. Systematic review of 20 studies showed that older age, female sex and lower education were risk factors for CI. Potential reversible factors for CI include electrolytes disturbances, depression and vitamin D deficiency. Also, CI was associated with a higher risk of hospitalization, mostly due to PD-related peritonitis. CONCLUSIONS: CI is common in patients on long-term PD. Screening for CI should be considered in PD patients with increased risk.

Prevalence of hyperphagia in Alzheimer's disease: a meta-analysis.

BACKGROUND: Unlike other behavioural and psychological symptoms of dementia, hyperphagia is less recognized among patients with Alzheimer's disease (AD). The prevalence of hyperphagia varies among studies, but there has been no systematic review or meta-analysis. METHODS: An extensive search on the literature on hyperphagia in AD published between 1 January 1980 and 30 October 2017 was conducted. Data on the prevalence were retrieved. Meta-analysis with a random effect model was performed to determine the pooled estimate of prevalence. Meta-regression analysis was performed based on study characteristics, population demographics, or condition information. RESULTS: Results from 20 studies were extracted. Twenty-six reported cases of hyperphagia were identified. The mean age of onset was 70.7 ± 8.9 years, with a male predominance (68.4%). Hyperphagia occurred in all stages of AD. Only eight studies reported the prevalence of hyperphagia. Meta-analysis showed a pooled prevalence of hyperphagia of 18.6%. Publication bias may have been present. Meta-regression showed that ethnicity accounted for the variance among studies (coefficient: -1.247 (95% confidence interval: -1.978 to -0.516), R2 analogue: 0.77, P < 0.001). CONCLUSIONS: Hyperphagia occurs in all stages of AD. In this meta-analysis of eight published studies, the prevalence of hyperphagia was 18.6%. In view of the possible publication bias, a large-scale study on hyperphagia is recommended in the future.

Association between high cumulative dose of benzodiazepine in Chinese patients and risk of dementia: a preliminary retrospective case-control study.

BACKGROUND: Evidence describing the association between high-dose benzodiazepine use and dementia has been conflicting. Most previous studies involved Caucasian populations, with only limited data on Chinese subjects. Possible differences exist between Chinese and Caucasian populations with regard to metabolism and prescription practice. This study aimed to assess the association between high-dose benzodiazepine use and dementia in a Chinese population. METHOD: A retrospective case-control study was carried out in all public hospitals under the Hong Kong Hospital Authority Hong Kong West Cluster between 2000 and 2015. The study recruited 273 Chinese adults (91 cases, 182 controls) aged 75 and over, with at least 6 years of follow-up data. Each dementia case was matched with two controls according to sex, age group, and duration of follow-up. The number of patients with benzodiazepine ever-use and the exposure density based on the prescribed daily doses were assessed. Prescribed daily doses were categorized as either <1096 or ≥1096. Odds ratios and 95% confidence intervals were computed by multivariate analysis. RESULTS: The difference in exposure density between the dementia and control groups was statistically significant between prescribed daily doses <1096 and ≥1096 (P = 0.02). There were two multivariate analyses models; one factored in depression (model 1), and the other (model 2) did not. Model 2 showed a statistically significant association (odds ratio = 1.71, 95% confidence intervals = 1.02-2.89, P = 0.04) between benzodiazepine exposure density and dementia. CONCLUSION: High-dose benzodiazepine use may be associated with dementia in the Chinese population. Prospective studies are required.

Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

BACKGROUND: Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. METHODS: Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. RESULTS: 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45% were female. The prevalence of CI was 13.9% using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p < 0.001), lower CMMSE (p < 0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p < 0.001). Compared with self-care PD patients, assisted PD patients did not have higher rates exit site infection (p = 0.30) but had a trend of higher PD peritonitis (p = 0.07). CONCLUSION: CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences.

There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p < 0.001) and were more commonly affected by seizures, spastic paraparesis, myoclonus, and cerebellar signs (p < 0.001, p < 0.001, p = 0.003, and p = 0.002, respectively). Patients with PSEN2 mutations have a delayed AOO with longest disease duration and presented more frequently with disorientation (p = 0.03). Patients with amyloid precursor protein (APP) mutations presented more frequently with aggression (p = 0.02) and those with APP duplication presented more frequently with apraxia (p = 0.03). PSEN1 mutations before codon 200 had an earlier AOO than those having mutations after codon 200 (41.4 ± 8.0 years vs. 44.7 ± 8.7 years, p < 0.001). Because 42.9% of the mutations reported are novel, the mutation spectrum and clinical features in Asian FAD families could be different from that of whites. Asian patients with PSEN1 mutations presented more frequently with disorientation (p = 0.02) and personality change (p = 0.01) but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites.

Comparisons of clinical symptoms in biomarker-confirmed Alzheimer's disease, dementia with Lewy bodies, and frontotemporal dementia patients in a local memory clinic.

BACKGROUND: There has been no previous Chinese study that differentiated the clinical symptoms among biomarker-confirmed Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). The objective of this study was to compare the cognitive, behavioural, and neuropsychiatric symptoms in biomarker-confirmed AD, DLB, and FTD patients. METHODS: We recruited 30 patients (14 AD, 7 DLB, 9 FTD) who presented to the memory clinic at Queen Mary Hospital from 1 January 2007 to 31 December 2013. AD was diagnosed according to the National Institution of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria with cerebrospinal fluid biomarkers (tau, phosphorylated tau, and amyloid ß-42) fulfilling locally determined cut-off values for AD. DLB was diagnosed based on the McKeith diagnostic criteria. The behavioural variant of FTD was diagnosed based on the revised diagnostic criteria proposed by the International bvFTD Criteria Consortium, and language variant FTD was diagnosed based on the latest published criteria. In addition, patients with DLB and FTD had typical imaging features on single-photon emission computed tomography or (18) fludeoxyglucose-positron emission tomography, either with or without Pittsburgh Compound B imaging, which supported their diagnoses. Data on patient characteristics including demographics, presenting clinical features, Mini-Mental State Examination, clinical dementia ratings, and neuropsychiatry inventory scores were collected. RESULTS: There were no differences in age, education level, dementia severity, and duration of symptoms before presentation among the three subgroups of patients. All patients had amnesia symptoms, which were not statistically significant. Apraxia was most common in AD. While 83% of the patients were affected by behavioural and neuropsychiatric symptoms of dementia, behavioural disinhibition and decline in executive function were most common in FTD patients. Recurrent hallucinations, fluctuation of consciousness, parkinsonism, and rapid eye movement sleep behaviour disorder were most common in DLB. CONCLUSION: Memory impairment and apathy are not useful discriminative symptoms in diagnosing AD, DLB, and FTD. Apraxia favours AD. Hallucinations, particularly well-formed visual hallucinations, favour DLB. Overall, behavioural and neuropsychiatric symptoms of dementia symptoms are common among the three groups of dementia patients.

Performance of GPT-4 and GPT-3.5 in generating accurate and comprehensive diagnoses across medical subspecialties.

Artificial intelligence has demonstrated a promising potential for diagnosing complex medical cases, with Generative Pre-Trained Transformer 4 (GPT-4) being the most recent advancement in this field. This study evaluated the diagnostic performance of the GPT-4 in comparison with that of its predecessor, GPT-3.5, using 81 complex medical case records from the New England Journal of Medicine . The cases were categorized as cognitive impairment, infectious disease, rheumatology, or drug reactions. The GPT-4 achieved a primary diagnostic accuracy of 38.3%, which improved to 71.6% when differential diagnoses were included. In 84.0% of cases, primary diagnoses were made by conducting investigations suggested by GPT-4. GPT-4 outperformed GPT-3.5 in all subspecialties except for drug reactions. GPT-4 demonstrated the highest performance in infectious diseases and drug reactions, whereas it underperformed in cases of cognitive impairment. These findings indicate that GPT-4 can provide reasonably accurate diagnoses, comprehensive differential diagnoses, and appropriate investigations. However, its performance varies across subspecialties.

Limitations of GPT-4 as a geriatrician in geri-oncology case conference: A case series.

Generative pre-trained transformer 4 (GPT-4) is an artificial intelligence (AI) system with a chat interface. The number of studies testing GPT-4 in clinical applications has been increasing. We hypothesized that GPT-4 would be able to suggest management strategies for medical issues in elderly oncology patients, similar to those provided by geriatricians. We compared the responses of GPT-4 to those of a geriatrician for four oncological patients. After these case conferences, none of the patients required admission for medical consultation. In three out of four scenarios, GPT-4 was able to offer a multidisciplinary approach in the first prompt. In all three scenarios, GPT-4 identified medication-related side effects and suggested appropriate medications in the first prompt. However, GPT-4 was unable to suggest initial dosages of medications to be used in the first prompt and was unable to suggest a more humanistic and non-pharmacological approach to anorexia, even with a follow-up prompt. In conclusion, GPT-4 may be used as a screening tool to provide potential rudimentary directions for management, which can then be reviewed by medical professionals before considering a formal consultation for more tailored and refined opinions from specialists.

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.