Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer's disease evaluated by ß-amyloid positron emission tomography imaging.

OBJECTIVE: We evaluated the effects of bone marrow-derived mesenchymal stem cells in a model of Alzheimer's disease using serial [18F]Florbetaben positron emission tomography. METHODS: 3xTg Alzheimer's disease mice were treated with intravenously injected bone marrow-derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and ß-amyloid-reactive cells. RESULTS: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow-derived mesenchymal stem cells-treated group (n = 28). In contrast, there was no change in the ratio in control mice (n = 25) at any time point. In addition, mice that received bone marrow-derived mesenchymal stem cell therapy also exhibited significantly better memory function and less ß-amyloid-immunopositive plaques compared to controls. CONCLUSION: The therapeutic effect of intravenously injected bone marrow-derived mesenchymal stem cells in a mouse model of Alzheimer's disease was confirmed by ß-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.

Low Testosterone Level as a Predictor of Poststroke Emotional Disturbances: Anger Proneness and Emotional Incontinence.

BACKGROUND: The role of sex hormones in poststroke mood and emotional disturbances is unclear. We aimed to evaluate the impact of sex hormones on poststroke emotional disturbance, especially anger proneness (AP) and emotional incontinence (EI). We also investigated whether statins, which are widely used for stroke prevention, affect sex hormone levels or the presence of poststroke AP/EI based on the hypothesis that intensive treatment with statins would inhibit the synthesis of cholesterol, the preferred substrate of testosterone. METHODS: We prospectively enrolled 40 patients who experienced ischemic stroke at least 3 months prior to study enrollment. We performed clinical and laboratory evaluations, including hormone-level measurements and neuropsychological tests. Poststroke AP and EI were assessed using interviews, then patients were divided into 2 groups: AP/EI-present or absent. RESULTS: Of the 40 patients (30 men, mean age 58.8 years), 16 (40.0%) were classified as AP/EI-present group. AP/EI were not related to stroke severity or location; however, the testosterone level was significantly lower in patients with AP/EI than in those without AP/EI (2.1 ± 1.7 vs. 3.9 ± 2.5 ng/mL, P = .023). After adjusting for potential confounding variables, low testosterone levels were a significant independent predictor of AP/EI (odds ratio .68, 95% confidence interval .49-.96, P = .027). In contrast, sex hormone levels and AP/EI prevalence did not differ between statin users and nonusers. CONCLUSIONS: AP/EI were associated with low testosterone levels in patients with previous ischemic stroke, but statin use did not affect AP/EI prevalence.

Cigarette smoking is an independent risk factor for post-stroke delirium.

BACKGROUND: Post-stroke delirium is a common problem in the care of stroke patients, and is associated with longer hospitalization, high short-term mortality, and an increased need for long-term care. Although post-stroke delirium occurs in approximately 10 ~ 30% of patients, little is known about the risk factors for post-stroke delirium in patients who experience acute stroke. METHODS: A total of 576 consecutive patients who experienced ischemic stroke (mean age, 65.2 years; range, 23-93 years) were screened for delirium over a 2-year period in an acute stroke care unit of a tertiary referral hospital. We screened for delirium using the Confusion Assessment Method. Once delirium was suspected, we evaluated the symptoms using the Korean Version of the Delirium Rating Scale-Revised-98. Neurological deficits were assessed using the National Institutes of Health Stroke Scale at admission and discharge, and functional ability was assessed using the Barthel Index and modified Rankin Scale at discharge and 3 months after discharge. RESULTS: Thirty-eight (6.7%) patients with stroke developed delirium during admission to the acute stroke care unit. Patients with delirium were significantly older (70.6 vs. 64.9 years of age, P = .001) and smoked cigarettes more frequently (40% vs. 24%, P = .033) than patients without delirium. In terms of clinical features, the delirium group experienced a significantly higher rate of major hemispheric stroke (55% vs. 26%, P < .001), exhibited poorer functional performance at discharge and 3 months after discharge, and stayed in hospital significantly longer. Independent risk factors for delirium were older age, history of cigarette smoking, and major hemispheric stroke. CONCLUSION: Abrupt cessation of cigarette smoking may be a risk factor for post-stroke delirium in ischemic stroke patients. The development of delirium after stroke is associated with worse outcome and longer hospitalization.

Card-placing test in amnestic mild cognitive impairment and its neural correlates.

BACKGROUND: [corrected] We investigated anatomical correlates of the card-placing test (CPT) in patients with amnestic mild cognitive impairment (aMCI). METHODS: Fifteen aMCI patients underwent part A and part B of the CPT and FDG-PET. The CPT scores and MMSE scores of 29 cognitively normal people were used for comparison. Statistical parametric mapping (SPM) correlation analysis was used to extract the regions whose changes in regional cerebral metabolism correlated significantly with part A and B of the CPT with adjustment of age, education and sex of patients. RESULTS: The aMCI patients had significantly lower MMSE scores (26.0 ± 2.0 vs. 28.2 ± 1.4, p < 0.001), CPT A (25.5 ± 3.5 vs. 27.7 ± 2.7, p = 0.026) and CPT B scores (16.3 ± 4.4 vs. 19.7 ± 3.7, p = 0.011) compared to the normal population. The test scores of part B of the CPT correlated well with hypometabolism of the posterior cingulate gyrus and precuneus. CONCLUSIONS: This study suggests that the CPT B may reflect the functional status of the posterior cingulate gyrus in patients with aMCI.

Evaluation of coexistence of Alzheimer's disease in idiopathic normal pressure hydrocephalus using ELISA analyses for CSF biomarkers.

BACKGROUND: We investigated levels of the ß-amyloid 1-42 (Aß42), total tau protein (T-tau) and tau phosphorylated at position threonine 181 (P-tau) in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (iNPH) patients and tried to find their clinical implications in the evaluation and treatment of iNPH. METHOD: Twenty-five possible iNPH patients were prospectively enrolled and their CSF was collected to analyze levels of Aß42, T-tau and P-tau using ELISA method. Gait disturbance, urinary incontinence, and cognitive impairment were semi-quantified and detailed neuropsychological (NP) test was performed. RESULT: Eight iNPH patients were classified into the lower CSF Aß42 group and 17 patients were classified into the higher CSF Aß42 group. There was no difference in the iNPH grading score and its improvement after LP between the two groups. The lower CSF Aß42 group showed more deficits in attention, visuospatial function and verbal memory in the baseline NP test and less improvement in phonemic categorical naming and frontal inhibitory function after LP. CONCLUSIONS: Our study suggested that concomitant AD in iNPH patients might contribute to lumbar puncture or shunt unresponsiveness, especially in the field of cognitive dysfunction.

Clustering mild cognitive impairment by mini-mental state examination.

We aimed to evaluate whether the performance of the mini-mental state examination (MMSE) could identify risky mild cognitive impairment (MCI). We recruited 122 amnestic MCI-single domain (ASM), 303 amnestic MCI-multiple domains (AMM), and 94 non-amnestic MCI (NAM). Two-step cluster and linear discriminant analyses were used for identifying the clusters of the MMSE with age and education, as well as establishing prediction models for each cluster. Conversion into dementia was compared among clusters. Cluster analyses revealed the following three: cluster 1 = 205 AMM (100 %); cluster 2 = 61 NAM (33.3 %) and 122 ASM (66.7 %); and cluster 3 = 33 NAM (25.2 %) and 98 AMM (74.8 %). Cluster 3 showed a significantly lower ability with regards to orientation to time and place, registration of three words, attention/calculation, language, and copying interlocking pentagons, than clusters 1 and 2. However, for delayed recall, cluster 1 was significantly more impaired than cluster 2. Patients in the cluster 1 showed the most common conversion into dementia [odds ratio (OR) = 2.940 vs. cluster 2, OR = 2.271 vs. cluster 3]. This study showed that clustering by performance in MMSE could help define groups at higher risk for conversion to dementia. Therefore, MMSE can be considered as a promising screening tool including subtyping for MCI when detailed neuropsychological tests are not feasible.

Galantamine administration in chronic post-stroke aphasia.

BACKGROUND: To investigate the influence of galantamine on linguistic function, any associated factors in patients with chronic post-stroke aphasia were analysed. METHODS: 45 patients younger than 75 years with chronic aphasia (≥1 year since onset) were prospectively enrolled in the study. Language testing was performed at weeks 0 and 16. Initial galantamine dose was 8 mg/day for 4 weeks, and 16 mg/day for the following 12 weeks. Efficacy was evaluated by the sum of four domains (spontaneous speech, comprehension, repetition and naming) on the aphasia quotient (AQ) of the Western Aphasia Battery from baseline (AQ1) to endpoint (AQ2). Patients were considered as 'responding' if the increase in AQ was ≥20. RESULTS: Mean age was 60.4 years (22-74) and 14 patients were female. Mean duration of aphasia was 2.2±1.5 years. There was a significant increase in the total AQ score in the galantamine group (n=23, 48.5-57.0 percentile; p=0.007) but not in the control group (n=22, 54.3-54.9 percentile; p=0.308). The AQ2 score was independently associated with AQ1, galantamine administration and Mini-Mental State Examination (MMSE) score in multiple linear regression models. With the galantamine group, the good responders (vs poor responders) had a higher level of education (p=0.048), higher baseline MMSE score (p=0.009) and a subcortical dominant pattern (p=0.030). After adjusting for potential variables, subcortical dominant lesion was the independent determinant for galantamine responsiveness (OR 30.3; 95% CI 1.1 to 805.9, p=0.041). CONCLUSION: Administration of galantamine had a beneficial effect on chronic post-stroke aphasia, and was more prominent in subcortical dominant lesions.

Posterior circulation embolism as a potential mechanism for migraine with aura.

BACKGROUND: Although the mechanism of migraine is regarded as a functional disorder of the brain, numerous studies have reported that migraine is closely associated with vascular system abnormalities. CASE REPORTS: We describe a 19-year-old female with recurrent migraine attacks and typical aura for 7 years. MRI showed multiple stroke lesions in the posterior circulation. Moreover, a pseudoaneurysm (1.9 × 1.4 cm) originating from the left vertebral artery was observed on four-vessel angiography. Multiple microembolic signals (MES) were repeatedly observed in the basilar artery using 30-minute transcranial Doppler monitoring. Interestingly, MES and her typical migrainous symptoms disappeared simultaneously with removal of the pseudoaneurysm. DISCUSSION: This case supports the fact that microemboli play a pivotal role in the development of migraine attacks.

Metabolite investigation in both anterior and posterior cingulate gyri in Alzheimer's disease spectrum using 3-tesla MR spectroscopy.

AIMS: In order to evaluate the metabolite changes of both anterior and posterior cingulate gyri during the progression of Alzheimer's disease (AD) pathology, a 3-tesla MR spectroscopy study was performed. METHODS: Thirty-six patients with AD, 19 patients with amnestic mild cognitive impairment (aMCI), and 23 cognitively normal (CN) subjects were recruited. MR spectroscopy was conducted within the anterior and posterior cingulate gyri. A one-way analysis of co-variance was used to compare the metabolite ratios of each group and correlation analysis was used to show the correlation between the metabolite ratios with the Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI). RESULTS: The N-acetylaspartate/creatine (NAA/Cr) of the posterior cingulate gyrus was significantly higher in CN subjects than in aMCI and AD patients. On the other hand, the myoinositol/creatine (ml/Cr) of the anterior cingulate gyrus was significantly higher in AD patients than in CN subjects and aMCI patients. The ml/Cr of the posterior cingulate gyrus correlated with the MMSE and that of the anterior cingulate gyrus correlated with the NPI. CONCLUSION: Both the decreased NAA/Cr of the posterior cingulate gyrus and the increased ml/Cr of the anterior cingulate gyrus may reflect biochemical changes in AD according to the posterior-dominant progression of AD pathology.

Functional investigation of bilateral posterior cingulate gyri using multivoxel MR spectroscopy.

The exact functional correlation of each hemisphere's posterior cingulate gyrus with the symptoms of Alzheimer's disease (AD) remains unknown. We attempted to evaluate the relationship between metabolite ratios in each hemisphere's posterior cingulate gyrus and cognitive deficits, using multivoxel magnetic resonance spectroscopy (MRS). We recruited 23 patients with AD, 16 patients with amnestic mild cognitive impairment and 22 cognitively normal subjects. All patients underwent multivoxel MRS in the bilateral posterior cingulate gyri. We statistically analyzed correlations between the N-acetylaspartate/creatine ratio (NAA/Cr) in each posterior cingulate gyrus and patients' raw scores on neuropsychological tests. The NAA/Cr of each posterior cingulate gyrus correlated well with the verbal learning test scores on immediate recall and delayed recall tasks. We found that the only cognitive domain to correlate with the NAA/Cr of each posterior cingulate gyrus was verbal memory. Our results did not show any significant functional difference between right and left posterior cingulate gyri.

Pentobarbital coma therapy for super-refractory status epilepticus and in-hospital mortality: an observational study.

Treatment of super-refractory status epilepticus (SRSE) is associated with various complications of anaesthetic coma therapy. This study aimed to describe the factors affecting the prognosis, especially in-hospital mortality, of patients receiving pentobarbital coma therapy for the treatment of SRSE. This was a retrospective cohort study conducted in a single tertiary referral centre with patients who received pentobarbital coma therapy for the treatment of SRSE from 2006 to 2018. Exploratory analyses were performed for clinical, laboratory, electrographic, and radiological factors for the entire cohort and were compared between the mortality and survivor groups. In total, 19 patients were enrolled, and five (26.3%) patients died in the hospital. The maximal pentobarbital infusion dose was higher in the mortality group than in the survivor group (4.4±1.0 mg/kg/h vs. 2.9±1.4 mg/kg/h, respectively; p=0.025). The high-dose pentobarbital infusion group (>3.75 mg/kg/h) underwent longer mechanical ventilation (24 [20-36.75] vs. 41 [28-70], p=0.025) and blood culture results were more frequently positive, suggestive of septicaemia (8.3% vs. 57.1%, p=0.038). The group of SRSE patients treated with pentobarbital coma therapy who died in the hospital received a higher pentobarbital infusion dose compared to survivors; a complication of high-dose pentobarbital infusion was septicaemia. Considering the high rate of septicaemia observed, systematic treatment strategies focusing on infectious complications should be established and implemented. The association between maximal pentobarbital infusion dose and in-hospital mortality needs to be further validated.

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation.

BACKGROUND: Recently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. METHODS: In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson's disease, and 32 healthy control (HC) were collected. CSF amyloid-ß1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. RESULTS: CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson's disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-ß1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-ß1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer's disease pathophysiology, all A-T+N+ patients with N/αS+ were reintegrated into AD. CONCLUSIONS: The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.

Serum cholesterol levels and the risk of multiple system atrophy: a case-control study.

Cholesterol in brain membranes may modulate the conformational state and accumulation of alpha-synuclein in alpha-synucleinopathies.We examined the association between serum cholesterol and the risk of multiple system atrophy (MSA), one of the alpha-synucleinopathies. We enrolled 142 patients with probable MSA from two tertiary referral hospitals and 155 age- and gender-matched healthy people with no neurological disease. The levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in MSA patients than in controls (total cholesterol: 172.7 vs. 196.3 mg/dL, P < 0.001; LDL-C: 104.0 vs. 115.3 mg/dL, P = 0.001; HDL-C: 47.3 vs. 54.2 mg/dL, P < 0.001). After adjusting for age, gender, use of cholesterol-lowering drugs, and histories of hypertension, diabetes mellitus, and smoking, the odds ratios was 5.9 (95% CI = 2.3-11.5, P < 0.001) for MSA patients in the lowest quartile of total cholesterol and 2.6 (95% CI = 1.2-5.5, P = 0.016) for those in the lowest quartile of HDL-C, compared with the highest quartiles. Levels of serum cholesterol did not significantly correlate with disease duration or severity. Our data suggest that lower levels of total cholesterol and HDL may be associated with an increased risk of MSA.

Clinical and Demographic Predictors of Adverse Outcomes in Caregivers of Patients with Dementia.

BACKGROUND AND PURPOSE: We aimed to elucidate independent predictors of adverse outcomes in caregivers of patients with dementia using readily available clinical and demographic data of patients with dementia and their caregivers. METHODS: We reviewed patient-caregiver data from the Clinical Research Center for Dementia of South Korea and Caregivers of Alzheimer Disease Research study. The clinical factors of the patients and the demographics of both patients and caregivers were used to predict adverse outcomes for caregivers. Correlation and linear regression analyses were performed. RESULTS: We enrolled 454 patients and their caregivers for the present study. The general burden for the caregiver was higher amongst female caregivers, patients with further decreased the level of activities of daily living (ADL), patients with more abnormal behavior, or younger patients. The time spent by the caregivers was more in cases of patients with higher Caregiver Administered Neuropsychiatric Inventory scores, younger patients and for patients with decreased level of ADL. Depression amongst caregivers was more prominent in patients with higher Clinical Dementia Rating Sum of Boxes scores. Physical health-related quality of life (HRQoL) was lower in female caregivers, more physically affected patients, and older caregivers. Lastly, mental HRQoL was lower in younger, more physically affected, and in patients with abnormal behaviors. CONCLUSIONS: Clinical and demographic characteristics of patients and caregivers predict adverse outcomes for caregivers. Therefore, these factors should be considered to provide support to both patients and their caregivers.

Cerebrospinal Fluid Levels of ß-Amyloid 40 and ß-Amyloid 42 are Proportionately Decreased in Amyloid Positron-Emission Tomography Negative Idiopathic Normal-Pressure Hydrocephalus Patients.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) could be misleading in idiopathic normal-pressure hydrocephalus (iNPH). We therefore investigated the CSF biomarkers in 18F-florbetaben amyloid-negative positron-emission tomography (PET) [amyloid PET(-)] iNPH, amyloid-positive PET [amyloid PET(+)] AD, and cognitively normal (CN) subjects. METHODS: Ten amyloid PET(+) AD patients (56.7±5.6 years old, mean±standard deviation), 10 amyloid PET(-) iNPH patients (72.8±4.5 years old), and 8 CN subjects (61.2±6.5 years old) were included. We measured the levels of ß-amyloid (Aß)40, Aß42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays. RESULTS: The level of Aß42 and the Aß42/Aß40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The Aß40 level did not differ significantly between AD and iNPH (p=1.000), but it did between AD and CN subjects (p=0.032). The levels of both t-tau and p-tau were higher in AD than in iNPH or CN subjects. The levels of Aß42, Aß40, t-tau, and p-tau were lower in iNPH than in CN subjects, but there was no significant difference after controlling for age. CONCLUSIONS: Our results suggest that the mechanism underlying low CSF Aß levels differs between amyloid PET(-) iNPH and amyloid PET(+) AD subjects. The lower levels of all CSF biomarkers in iNPH patients might be due to reduced clearances from extracellular fluid and decreased brain metabolism of the periventricular zone in iNPH resulting from glymphatic dysfunction.

Movement disorders at a university hospital emergency room. An analysis of clinical pattern and etiology.

We prospectively evaluated the clinical features and etiologies of all common categories of movement disorder seen in the emergency room (ER) of an urban university hospital over a period of 12 months. We divided movement disorders according to the presenting phenomenology likely to dominate the clinical presentation, that is, gait disorder, tremor, dystonia, myoclonus, and acute akinetic crisis and classified a specific etiology in the individual phenomenology. In one year, there were 60,002 ER visits; of these, 58 (0.09 %) were diagnosed as a primary movement disorder. The most common clinical presentation was gait disorder (n = 21, 36.2 %), followed by myoclonus (n = 16, 27.6 %), dystonia (n = 10, 17.2 %), tremor (n = 8, 13.8 %), and acute akinetic crisis (n = 3, 5.2 %). Comparing the movement disorders, the mean age of the patients with dystonia was significantly lower than that of patients with other movement disorders (P < 0.001). Of the patients, 37 (63.8 %) had drug-related movement disorders. The contribution of drugs was significantly higher in patients with dystonia compared with the other movement disorders (P < 0.01). Our study showed that a large proportion of the movement disorders seen in the ER are drug-related. Careful selection of drugs while prescribing would decrease movement disorder-related visits to the ER.

In vivo tracking of intravenously injected mesenchymal stem cells in an Alzheimer's animal model.

PURPOSE: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer's disease (AD) animal model. METHODS: Stem cells were collected from bone marrow of mice and labeled with Indium-111 (111In). The 111In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells. RESULTS: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group. CONCLUSIONS: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.

Predictors of Institutionalization in Patients with Alzheimer's Disease in South Korea.

BACKGROUND AND PURPOSE: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92-0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00-1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06-1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20-2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.

The Brain Donation Program in South Korea.

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Differentiating cognitive impairment due to corticobasal degeneration and Alzheimer disease.

OBJECTIVE: To identify clinical features that reliably differentiate individuals with cognitive impairment due to corticobasal degeneration (CBD) and Alzheimer disease (AD). METHODS: Clinical features were compared between individuals with autopsy-proven CBD (n = 17) and AD (n = 16). All individuals presented with prominent cognitive complaints and were evaluated annually with semistructured interviews, detailed neurologic examinations, and neuropsychological testing. RESULTS: Substantial overlap was observed between individuals with dementia due to CBD and AD concerning presenting complaints, median (range) duration of symptoms before assessment (CBD = 3.0 [0-5.0] years, AD = 2.5 [0-8.0] years; p = 0.96), and median (range) baseline dementia severity (Clinical Dementia Rating Sum of Boxes: CBD = 3.5 [0-12.0], AD = 4.25 [0.5-9.0], p = 0.49). Subsequent emergence of asymmetric motor/sensory signs, hyperreflexia, gait abnormalities, parkinsonism, falls, urinary incontinence, and extraocular movement abnormalities identified individuals with CBD, with ≥3 discriminating features detected in 80% of individuals within 3.1 years (95% confidence interval 2.9-3.3) of the initial assessment. Individuals with CBD exhibited accelerated worsening of illness severity and declines in episodic memory, executive functioning, and letter fluency. Semiquantitative pathologic assessment revealed prominent tau pathology within the frontal and parietal lobes of CBD cases. Comorbid AD neuropathologic change was present in 59% (10 of 17) of CBD cases but did not associate with the clinical phenotype, rate of dementia progression, or dementia duration. CONCLUSIONS: CBD may mimic AD dementia early in its disease course. Interval screening for discriminating clinical features may improve antemortem diagnosis in individuals with CBD and prominent cognitive symptoms.