Dementia and Geriatric Cognitive Disorders最新文献

Introduction: Antipsychotics are still commonly prescribed to patients with dementia, despite the many issues that have been identified. This study aimed to quantify antipsychotic prescription in patients with dementia and the types of concomitant medications prescribed with antipsychotics.

Methods: A total of 1,512 outpatients with dementia who visited our department between April 1, 2013 and March 31, 2021, were included in this study. Demographic data, dementia subtypes, and regular medication use at the time of the first outpatient visit were investigated. The association between antipsychotic prescriptions and referral sources, dementia subtypes, antidementia drug use, polypharmacy, and prescription of potentially inappropriate medications (PIMs) was evaluated.

Results: The antipsychotic prescription rate for patients with dementia was 11.5%. In a comparison of dementia subtypes, the antipsychotic prescription rate was significantly higher for patients with dementia with Lewy bodies (DLB) than for those with all other dementia subtypes. In terms of concomitant medications, patients taking antidementia drugs, polypharmacy, and PIMs were more likely to receive antipsychotic prescriptions than those who were not taking these medications. Multivariate logistic regression analysis showed that referrals from psychiatric institutions, DLB, N-methyl-d-aspartate (NMDA) receptor antagonists, polypharmacy, and benzodiazepine were associated with antipsychotic prescriptions.

Conclusions: Referrals from psychiatric institutions, DLB, NMDA receptor antagonist, polypharmacy, and benzodiazepine were associated with antipsychotic prescriptions for patients with dementia. To optimise prescription of antipsychotics, it is necessary to improve cooperation between local and specialised medical institutions for accurate diagnosis, evaluate the effects of concomitant medication administration, and solve the prescribing cascade.

Introduction: As disease-modifying therapies become available for Alzheimer's disease (AD), detection of AD in early stages of illness (mild cognitive impairment [MCI], early dementia) becomes increasingly important. Biomarkers for AD in low- and middle-income countries (LMICs) are costly and not widely available; hence, it is important to identify cognitive tests that correlate well with AD biomarker status. In this study, we evaluated the memory alteration test (M@T) to detect biomarker-proven AD and quantify its correlation with neurodegeneration and cerebrospinal fluid (CSF) AD biomarkers in a cohort of participants from Lima, Peru.

Methods: This is a secondary analysis of a cohort of 185 participants: 63 controls, 53 with amnestic MCI (aMCI), and 69 with dementia due to AD. Participants underwent testing with M@T and a gold standard neuropsychological battery. We measured total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (β-amyloid) in CSF, and evaluated neurodegeneration via medial temporal atrophy score in MRI. We used receiver-operator curves to determine the discriminative capacity of the total M@T score and its subdomains. We used the Pearson coefficient to correlate M@T score and CSF biomarkers.

Results: The M@T had an area under the curve (AUC) of 0.994 to discriminate between controls and cognitively impaired (aMCI or AD) patients, and an AUC of 0.98 to differentiate between aMCI and AD patients. Free-recall and cued recall had the highest AUCs of all subdomains. Total score was strongly correlated with t-tau (-0.77) and p-tau (-0.72), and moderately correlated with β-amyloid (0.66). The AUC for discrimination of neurodegeneration was 0.87.

Conclusion: The M@T had excellent discrimination of aMCI and dementia due to AD. It was strongly correlated with CSF biomarkers and had good discrimination of neurodegeneration. In LMICs, the M@T may be a cost-effective screening tool for aMCI and dementia caused by AD.

Introduction: Sensorineural hearing loss is a common problem, especially among geriatric patients, and it requires hearing aids. Unfortunately, most geriatric patients are hesitant to use hearing aids. The purpose of this study was to investigate whether computerized training therapies increase the attention and perception of patients who have been given hearing aids using psychophysiological tests and wave P300 records.

Methods: One hundred patients (40 women and 60 men) who used hearing aids were included in our study. Sixty patients (30 women and 30 men) received computerized training therapies with hearing aids. After the psychophysiological tests, the study group was divided into three groups according to the role given to patients. Passive training was given in group 1; interactive training was given in group 2; and group 3 was active, questioning training. Measurements of P300 wave latencies, stimuli-P300 peak, and baseline-P300 peak were performed before and after training. The control group consisted of 40 patients who did not receive training and were treated with hearing aids only.

Results: We found a significant difference between the pre- and post-training measures of the P300 wave (p < 0.001). Pre-training measurements of P300 waves were recorded for 12% in group 1 and 9.1% in groups 2 and 3 (p = 0.24). Post-training measurements of the P300 wave records were 80% in group 1 and 72.7% in groups 2 and 3 (p = 0.22).

Conclusion: Attention and perception can be measured with the P300 wave. All computer-supported training programs showed an increase of the P300 wave, suggesting that attention and perception of patients with hearing loss can be increased with computer-supported training programs provided with hearing aids.

Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education.

Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models.

Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14-0.55) for dementia and 0.18 (0.07-0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60-74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38-0.69) for MCI and 0.46 (0.33-0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI.

Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.

Background: Cardiovascular disease (CVD), including elevated blood pressure (BP), is known to promote Alzheimer's disease (AD) risk. Although brain amyloid load is a recognized hallmark of pre-symptomatic AD, its relationship to increased BP is less known. The objective of this study was to examine the relationship of BP to brain estimates of amyloid-β (Aβ) and standard uptake ratio (SUVr). We hypothesized that increased BP is associated with increased SUVr.

Methods: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we stratified BP according to the Seventh Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Classification (JNC VII). Florbetapir (AV-45) SUVr was derived from the averaged frontal, anterior cingulate, precuneus, and parietal cortex relative to the cerebellum. A linear mixed-effects model enabled the elucidation of amyloid SUVr relationships to BP. The model discounted the effects of demographics, biologics, and diagnosis at baseline within APOE genotype groups. The least squares means procedure was used to estimate the fixed-effect means. All analyses were performed using the Statistical Analysis System (SAS).

Results: In non-ɛ4 carrier MCI subjects, escalating JNC categories of BP was associated with increasing mean SUVr using JNC-4 as a reference point (low-normal (JNC1) p = 0.018; normal (JNC-1) p = 0.039; JNC-2 p = 0.018 and JNC-3 p = 0.04). A significantly higher brain SUVr was associated with increasing BP despite adjustment for demographics and biological variables in non-ɛ4 carriers but not in ɛ4-carriers. This observation supports the view that CVD risk may promote increased brain amyloid load, and potentially, amyloid-mediated cognitive decline.

Conclusion: Increasing levels of JNC classification of BP is dynamically associated with significant changes in brain amyloid burden in non-ɛ4 carriers but not in ɛ4-carrier MCI subjects. Though not statistically significant, amyloid burden tended to decrease with increasing BP in ɛ4 homozygote, perhaps motivated by increased vascular resistance and the need for higher brain perfusion pressure.

Introduction: This study aimed to develop novel machine learning models for predicting Alzheimer's disease (AD) and identify key factors for targeted prevention.

Methods: We included 1,219, 863, and 482 participants aged 60+ years with only sociodemographic, both sociodemographic and self-reported health, both the former two and blood biomarkers information from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Machine learning models were constructed for predicting the risk of AD for the above three populations. Model performance was evaluated by discrimination, calibration, and clinical usefulness. SHapley Additive exPlanation (SHAP) was applied to identify key predictors of optimal models.

Results: The mean age was 73.49, 74.52, and 74.29 years for the three populations, respectively. Models with sociodemographic information and models with both sociodemographic and self-reported health information showed modest performance. For models with sociodemographic, self-reported health, and blood biomarker information, their overall performance improved substantially, specifically, logistic regression performed best, with an AUC value of 0.818. Blood biomarkers of ptau protein and plasma neurofilament light, age, blood tau protein, and education level were top five significant predictors. In addition, taurine, inosine, xanthine, marital status, and L.Glutamine also showed importance to AD prediction.

Conclusion: Interpretable machine learning showed promise in screening high-risk AD individual and could further identify key predictors for targeted prevention.

Introduction: Carnosine can suppress secondary complications in diabetes and show robust neuroprotective activity against neurodegenerative diseases. Here, we report that carnosine ameliorates diabetes-associated cognitive decline in vivo through the modulation of autophagy.

Methods: A high-fat diet (HFD) and one intraperitoneal injection of 30 mg/kg streptozotocin (STZ) were used to induce type 2 diabetes mellitus in Sprague-Dawley rats. The rats were randomly divided into five groups: control (CON), HFD/STZ, and three intragastric carnosine treatment groups receiving low (100 mg/kg), medium (300 mg/kg), and high (900 mg/kg) doses over 12 weeks. Body weight, blood glucose levels, and cognitive function were continuously monitored. From excised rat hippocampi, we determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels; carnosine concentration; protein expressions of Akt, mTOR and the autophagy markers LC3B and P62 and performed histopathological evaluations of the cornu ammonis 1 region.

Results: The HFD/STZ group showed increased blood glucose levels and decreased body weight compared to the CON group. However, there were no significant differences in body weight and blood glucose levels between carnosine-treated and -untreated HFD-STZ-induced diabetic rats. Diabetic animals showed obvious learning and memory impairments in the Morris water maze test compared to the CON group. Compared to those in the HFD/STZ group, carnosine increased SOD activity and decreased MDA levels, increased hippocampal carnosine concentration, increased p-Akt and p-mTOR expression, decreased LC3B and P62 expression, alleviated neuronal injuries, and improved cognitive performance in a dose-dependent manner.

Conclusion: Independent of any hyperglycemic effect, carnosine may improve mild cognitive impairments by mitigating oxidative stress, activating the Akt/mTOR pathway, and modulating autophagy in the hippocampus of type 2 diabetic rats.

Introduction: Transcranial Doppler (TCD) sonography is a noninvasive tool for measuring cerebrovascular hemodynamics. Studies have reported alterations in cerebrovascular hemodynamics in normal aging, mild cognitive impairment (MCI), and dementia, as well as in different etiologies of dementia. This systematic review and meta-analysis was designed to investigate the relationship between cerebral blood velocity (CBv) and pulsatility index (PI) in the middle cerebral artery (MCA) in persons with MCI and dementia.

Methods: A systematic literature search was conducted in Pubmed, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL. The search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of 33,439 articles, 86 were reviewed in full-text, and 35 fulfilled the inclusion criteria.

Results: CBv was significantly lower and PI significantly higher in MCA in vascular dementia (VaD) and Alzheimer's disease (AD) compared to cognitively normal (CN) older persons. Also, CBv was lower in MCI compared to CN. There were no significant differences in CBv in MCA in AD compared with VaD, although PI was higher in VaD compared to AD.

Conclusion: Alterations in cerebrovascular hemodynamics are seen in AD, VaD, and MCI. While PI was slightly higher in VaD compared to AD, the reduction in CBv appears to be equally pronounced across neurodegenerative and vascular etiologies of dementia.

Introduction: Depression is often difficult to detect in long-term care (LTC) patients with major neurocognitive disorders (MNCD), and an observer-rated screening scale could facilitate assessments. This study aimed to establish the external validity and reliability of the Nursing Homes Short Depression Inventory (NH-SDI) in LTC patients with MNCD and to compare its estimates to the Cornell Scale for Depression in Dementia (CSDD), the most used scale for depression in MNCD.

Methods: A focus discussion group of experts assessed the content validity of the NH-SDI. Then, a convenience sample of 93 LTC patients with MNCD was observer-rated by trained nurses with the NH-SDI and CSDD. For 57 patients, a medical assessment of depression was obtained, and screening accuracy estimates were generated.

Results: The prevalence of depression was 8.8% as per reference standard. NH-SDI's content validity was judged acceptable with minor item wording modifications and specifications. The NH-SDI (cut-off ≥3) achieved 100% (95% confidence interval [CI]: 46-100%) sensitivity, 83% (95% CI: 69-91%) specificity, and 36% (95% CI: 14-64%) positive predictive value (PPV). The CSDD (cut-off ≥3) achieved 100% (95% CI: 46-100%) sensitivity, 75% (95% CI: 61-86%) specificity, and 28% (95% CI: 11-54%) PPV. No significant differences in areas under the receiver operating characteristic curve were found between scales. The NH-SDI and CSDD were highly correlated (rs = 0.913; p < 0.001) and reliable (ICC = 0.77; p < 0.001).

Conclusion: The NH-SDI appears valid and reliable in LTC patients with MNCD and quicker than the CSDD to rule out depression in a busy or short-staffed setting.