A case of diphenhydramine intoxication showing prolonged false positive tricyclic antidepressant in the urine assay.

Background: The urine immunochromatographic assay is a useful screening tool for patients suspected of acute drug intoxication in emergency conditions. Diphenhydramine intoxication shows symptoms similar to those of tricyclic antidepressant (TCA) intoxication. Case presentation: We examined a case of diphenhydramine intoxication showing cerebellar ataxia and prolonged false positive results for TCA in the urine. The urine TCA test showed persistently positive results even 60 h after the patient's initial drug screening. We observed negative conversion 90 h after the initial drug screening. Discussion: Considering the similarities of clinical symptoms between diphenhydramine and TCA intoxication, emergency physicians should consider the possibility of cross-reactivity in the diagnosis of a patient with unknown acute drug intoxication showing positive results of TCA immunochromatographic assay in the urine. Conclusion: The present case suggests that diphenhydramine overdose may cause cerebellar ataxia and show prolonged cross-reactivity as TCA in the urine.

[The peak latency prolongation of the blink reflex in a patient with trigeminal neuralgia of Meckel's cave mass]. / A pislogási reflexcsúcs latenciájának megnyúlása egy Meckel-barlang-terime következtében kialakuló trigeminusneuralgia esetben.

The blink reflex test of the trigeminal nerve can provide valuable information about lesions site. However it may not find small compressive lesions. We observed peak latency prolongation of the blink reflex test in a patient with trigeminal neuralgia caused by a small Meckel's cave mass, in whom the onset latency was normal. Conclusion - We suggest peak latency of the blink reflex might be a valuable aid for discerning small mass in patients with trigeminal neuralgia. This is the first case report of compressive trigeminal neuralgia showing peak latency prolongation of the blink reflex test.

Cognitive decline according to amyloid uptake in patients with poststroke cognitive impairment.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment (PSCI) is common, but the impact of ß-amyloid (Aß) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. METHODS: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A-) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12 months) between the A+ and A- groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12 months) between the A+ and A- groups. CONCLUSIONS: This study will provide a broadened perspective on the impact of Aß on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors. TRIAL REGISTRATION: Clinical Research Information Service identifier: KCT0005086.

Methodological considerations of evaluating the rate of presynaptic dopaminergic denervation in Parkinson disease with radiotracers: Analysis of the PPMI data.

ABSTRACT: Many previous studies have estimated the rate of dopaminergic denervation in Parkinson disease (PD) via imaging studies. However, they lack the considerations of onset age, disease duration at onset, gender, and dopaminergic denervation due to normal aging. Herein, using a large prospective cohort, we estimated the rate of dopaminergic denervation in PD patients, compared with an age- and gender-matched normal control group.One hundred forty-one normal controls and 301 PD patients were enrolled. Striatal specific binding ratios (SBRs) of I-123 FP-CIT single positron emission tomography images were analyzed according to the age of onset, gender, and the duration of motor symptoms.In the PD group, symptom duration was significantly correlated with caudate SBRs, but with putamen SBRs (P  < .05, R2 = 0.02). Moreover, was significantly inversely related to caudate SBRs, but not with putamen SBRs (P  < .05, R2 = 0.02). Patients of different age onsets did not show any significant correlation between symptom durations and striatal SBRs. In the age-matched group, no significant relationship was observed between symptom duration and percent decrease of caudate SBRs, but there was a significant relationship between symptom duration and percent decrease of the putamen SBRs (P  < .01, R2 = 0.06). There was no significant relationship between the symptom duration and the percent decrease of striatal SBRs in the age- and gender-matched group.The significance and R2 values from the regression analysis between symptom duration, age, and dopaminergic denervation are low. This suggests that, contrary to previous knowledge, there is a relatively weak association between dopaminergic denervation and age or symptom duration.

Patients with scans without evidence of dopaminergic deficit (SWEDD) do not have early Parkinson's disease: Analysis of the PPMI data.

BACKGROUND: To evaluate whether patients with scans without evidence of dopaminergic deficit (SWEDD) have early Parkinson's disease (PD). METHODS: The clinical characteristics, striatal specific binding ratios (SBRs), and the indices of I-123 FP-CIT SPECT images of 50 SWEDD patients, 304 PD patients, and 141 healthy controls were acquired from the Parkinson's Progression Markers Initiative (PPMI) data and evaluated during a 2-year clinical follow-up period. RESULTS: Of the 50 subjects with SWEDD, PD was confirmed in 13 subjects (the PD-SWEDD group), while the remaining 37 subjects had other diseases (the Other-SWEDD group). Striatal SBR values and striatal asymmetry indices of the PD group were significantly different with those of the PD-SWEDD and Other-SWEDD groups at both baseline and after 2 years (p < 0.001). Putaminal SBR values of the PD-SWEDD group were significantly decreased after 2 years (p < 0.05). There was no difference of the SBR values between baseline and after 2 years in the Other-SWEDD group. A baseline MDS-UPDRS III score matched comparison of the PD and PD-SWEDD group was done due to the large difference of the subject numbers. Striatal SBR values and striatal asymmetry indices were significantly different (p < 0.001) between the two groups at both baseline and after 2 years, but there were no significant difference with respect to the MDS-UPDRS III scores after 2 years between the two groups. CONCLUSION: The different SBR values and asymmetry indices between the PD and PD-SWEDD groups at baseline and after 2 years indicate that SWEDD may not be early PD, but rather a different disease entity.

Comparison of Urinary Alzheimer-Associated Neural Thread Protein (AD7c-NTP) Levels Between Patients With Amnestic and Nonamnestic Mild Cognitive Impairment.

Urinary Alzheimer-associated neural thread protein (AD7c-NTP) is a potential biomarker of Alzheimer disease (AD) or mild cognitive impairment (MCI). It is still unclear whether the urinary levels of AD7c-NTP are different between patients with amnestic MCI (aMCI) and nonamnestic MCI (naMCI). The present study aimed to explore the differences in urinary levels of AD7c-NTP between patients with aMCI and naMCI. Forty-six patients with MCI were divided into aMCI group (n = 23) and naMCI group (n = 23). The mean level of urinary AD7c-NTP in the aMCI group (32.75 ± 10.0 µg/mL) was significantly higher than that in the naMCI group (25.34 ± 9.0 µg/mL; P = .011). As far as we know, the present study is the first to show that individuals with aMCI have higher levels of urinary AD7c-NTP than those with naMCI, suggesting that urinary AD7c-NTP may be a potential biomarker to help identify patients with aMCI and naMCI.

Alteration of Tremor Dominant and Postural Instability Gait Difficulty Subtypes During the Progression of Parkinson's Disease: Analysis of the PPMI Cohort.

Background: Classifying PD into tremor dominant (TD) and postural instability gait difficulty (PIGD) subtypes may have several limitations, such as its diagnostic inconsistency and inability to reflect disease stage. In this study, we investigated the patterns of progression and dopaminergic denervation, by prospective evaluation at regular time intervals. Methods: 325 PD dopamine replacement drug-naïve patients (age 61.2 ± 9.7, M:F = 215:110) were enrolled. Patients were grouped into TD, indeterminant, and PIGD subtypes. Clinical parameters and I-123 FP-CIT SPECT images of each groups were analyzed and compared at baseline, 1, 2, and 4 years of follow up periods. Results: Baseline I-123 FP-CIT uptakes of the striatum were significantly higher in the TD group compared with the indeterminant group and PIGD group (p < 0.01). H & Y stage and MDS-UPDRS part III scores of the indeterminant group were significantly worse at baseline, compared with the TD and PIGD groups (p < 0.001 and p < 0.01, respectively), and MDS-UPDRS part II scores of the indeterminant group were significantly worse than the PIGD group (p < 0.001). There were no other significant differences of age, gender, weight, duration of PD, SCOPA-AUT, MOCA, usage of dopamine agonists, and levodopa equivalent daily doses at baseline. After 4 years of follow up, there were no differences of I-123 FP-CIT uptakes or clinical parameters, except for the MDS-UPDRS part II between the TD and indeterminant group (p < 0.05). The motor-subtypes were reevaluated at the 4 years period, and the proportion of patients grouped to the PIGD subtype increased. In the reevaluated PIGD group, MDS-UPDRS part II score (p < 0.001), SCOPA-AUT (p < 0.001), the proportion of patients who developed levodopa induced dyskinesia were higher than the reevaluated TD group, and the striatal I-123 FP-CIT uptakes were significantly lower (p < 0.01). Conclusion: There are no significant differences of symptoms and dopaminergic innervation between the TD and PIGD group after a certain period of follow up. Significant portion of patients switched from the TD subtype to the PIGD subtype during disease progression, and had a worse clinical prognosis.

Associated factors for cognitive impairment in the rural highly elderly.

BACKGROUND: Among the symptoms commonly faced by an increasingly aged population, dementia, preceded by cognitive impairment, most threatens their quality of life. Dementia is a well-recognized burden, not only for individuals who face the disease and for their families, but also for entire nation. AIMS: The purpose of this study was to identify associated factors for cognitive impairment in a very elderly population via a screening study design in Sokcho, a rural area in South Korea. METHODS: Trained nurses screened patients from 75-84 years of age for dementia using the Mini-Mental State Examination for Dementia Screening (MMSE-DS) and conducted interviews to determine their socioeconomic status, education level, and living conditions (i.e., with or without family). RESULTS: In total, 4,369 subjects (1,646 males, 2,723 females) were enrolled in this study. Reported MMSE-DS scores decreased with increasing age and to a greater degree in less educated subjects (p < 0.001). Subjects requiring medical assistance or living alone exhibited lower MMSE-DS scores compared to those who did not require medical assistance or who lived alone (p < 0.001). CONCLUSION: We found that less education, lower socioeconomic status, and living alone were associated factors for cognitive impairment based on this study of an elderly population.

The moderating effect of religiosity on caregiving burden and depressive symptoms in caregivers of patients with dementia.

OBJECTIVES: This study explored whether religiosity/spirituality has a protective role against negative caregiving outcomes, in a large multicenter nationwide sample of caregivers of patients with dementia in South Korea. Additionally, this study was the first to examine whether religiosity/spirituality could affect caregiving outcomes according to the various religious affiliations of caregivers. METHODS: The study was conducted on a sample of 476 caregivers of patients with dementia participated in the Clinical Research Center for Dementia of South Korea (CREDOS). We examined the moderating effect of each of the three dimensions of religiosity/spirituality (organizational religious activity, ORA; non-organizational religious activity, NORA; intrinsic religiosity, IR) on the relationship between activities of daily living (ADL) of patients with dementia and caregiving burden and depressive symptoms of caregivers, using a series of hierarchical regression analyses. In addition, these analyses were conducted according to the religious affiliations of the caregivers. RESULTS: ORA, NORA, and IR of religiosity/spirituality alleviated the effect of ADL of patients on caregiving burden. ORA and IR moderated the relationship between ADL of patients and depressive symptoms of caregivers. These moderating effects of religiosity on caregiving outcomes were different according to various religious groups. CONCLUSION: We have identified religiosity/spirituality as a protective factor for caregivers of patients with dementia. The sub-dimensions of religiosity as moderators were different by religious affiliations of caregivers. Further studies are needed to investigate the specific religiosity-related factors which could positively impact the mental health of the caregivers of patients with dementia by religions.

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial.

BACKGROUND AND OBJECTIVE: Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. METHODS: Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. RESULTS: Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. CONCLUSIONS: Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01380288.

Behavioural and neuropsychiatric disturbance in three clinical subtypes of frontotemporal dementia: A Clinical Research Center for Dementia of South Korea-FTD Study.

OBJECTIVES: To characterise the behavioural and neuropsychiatric disturbances of patients with three clinical subtypes of frontotemporal dementia (FTD): behavioural variant FTD (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). METHODS: Consecutive series of 66 patients with bvFTD, 58 patients with SD and 21 patients with PNFA were compared using the Frontal Behavioural Inventory (FBI) and the Neuropsychiatric Inventory (NPI). RESULTS: Patients with bvFTD had more behavioural and neuropsychiatric disturbances than patients with PNFA based on the total scores of FBI and NPI. When comparing subtotal and item scores of FBI and NPI, there were some significant differences among three clinical subtypes of FTD. CONCLUSION: There are some distinct patterns of behavioural and neuropsychiatric disturbance among three clinical subtypes of FTD.

Effect of galantamine on attention in patients with Alzheimer's disease combined with cerebrovascular disease.

AIM: Patients with Alzheimer's disease (AD) and cerebrovascular disease (CVD) show greater attentional deficits compared with AD patients without CVD. The aim of the present study was to investigate the effect of galantamine on attention in AD patients with CVD. METHODS: In this open trial, 1512 patients with AD and CVD were recruited from 71 nationwide hospitals. The patients were given galantamine for 16 weeks. The primary outcome measure was the score on the Attention Questionnaire Scale (AQS), which measures the patients' attention in their daily lives. The secondary outcome measures were the scores on the Korean Mini-Mental State Examination, the Clinical Dementia Rating scale and the Global Deterioration Scale. Efficacy measures were calculated both at baseline and at the end of the treatment (week 16). RESULTS: The responders rate on the AQS (change of the AQS from baseline >0) was 60.6% in AD patients with CVD. At the end of the treatment, both the AQS (15.0 ± 5.7 vs 16.3 ± 5.8, P < 0.001) and the Korean Mini-Mental State Examination scores (17.8 ± 4.8 vs 18.1 ± 5.1, P < 0.001) showed a significant improvement relative to the baseline performance. The Clinical Dementia Rating (1.25 ± 0.59 vs 1.22 ± 0.63 P = 0.025) and Global Deterioration Scale (3.82 ± 0.94 vs 3.76 ± 0.96, P = 0.002) scores also showed a significant decrease at the end of the treatment. CONCLUSIONS: Galantamine is effective in improving attention in the daily lives of AD patients with CVD. Geriatr Gerontol Int 2017; 17: 1661-1668.

Influence of personality on depression, burden, and health-related quality of life in family caregivers of persons with dementia.

BACKGROUND: Personality may predispose family caregivers to experience caregiving differently in similar situations and influence the outcomes of caregiving. A limited body of research has examined the role of some personality traits for health-related quality of life (HRQoL) among family caregivers of persons with dementia (PWD) in relation to burden and depression. METHODS: Data from a large clinic-based national study in South Korea, the Caregivers of Alzheimer's Disease Research (CARE), were analyzed (N = 476). Path analysis was performed to explore the association between family caregivers' personality traits and HRQoL. With depression and burden as mediating factors, direct and indirect associations between five personality traits and HRQoL of family caregivers were examined. RESULTS: Results demonstrated the mediating role of caregiver burden and depression in linking two personality traits (neuroticism and extraversion) and HRQoL. Neuroticism and extraversion directly and indirectly influenced the mental HRQoL of caregivers. Neuroticism and extraversion only indirectly influenced their physical HRQoL. Neuroticism increased the caregiver's depression, whereas extraversion decreased it. Neuroticism only was mediated by burden to influence depression and mental and physical HRQoL. CONCLUSIONS: Personality traits can influence caregiving outcomes and be viewed as an individual resource of the caregiver. A family caregiver's personality characteristics need to be assessed for tailoring support programs to get the optimal benefits from caregiver interventions.

Gender differences in risk factors for transition from mild cognitive impairment to Alzheimer's disease: A CREDOS study.

BACKGROUND: Women are subject to a disproportionate burden from Alzheimer's disease (AD) and sex differences exist in treatment response and prognosis of the disease. Yet gender-specific risk factors have not been widely studied. We aimed to investigate gender-specific risk factors for AD in subjects with mild cognitive impairment (MCI). METHODS: Participants (n=294) with MCI were recruited from a nationwide, prospective cohort study of dementia and were followed for a median (range) of 13.8 (6.0-36.0) months. Sex-stratified associations of progression to AD with baseline characteristics were explored. RESULTS: Seventy-four individuals (25.2%) developed incident dementia (67 AD) during follow-up. Significant risk factors for probable AD differed by sex. In men, the significant risk factors were severe periventricular white matter hyperintensities, and poorer global cognitive function. In women, older age, clinically significant depressive symptoms at baseline, and positive APOE ε4 alleles were the significant risk factors. CONCLUSIONS: Risk factors for progression from MCI to probable AD differed in men and women. These results may translate to gender-specific preventative or therapeutic strategies for patients with MCI.

The heterogeneity and natural history of mild cognitive impairment of visual memory predominant type.

We evaluate the longitudinal outcomes of amnestic mild cognitive impairment (aMCI) according to the modality of memory impairment involved. We recruited 788 aMCI patients and followed them up. aMCI patients were categorized into three groups according to the modality of memory impairment: Visual-aMCI, only visual memory impaired; Verbal-aMCI, only verbal memory impaired; and Both-aMCI, both visual and verbal memory impaired. Each aMCI group was further categorized according to the presence or absence of recognition failure. Risk of progression to dementia was compared with pooled logistic regression analyses while controlling for age, gender, education, and interval from baseline. Of the sample, 219 (27.8%) aMCI patients progressed to dementia. Compared to the Visual-aMCI group, Verbal-aMCI (OR = 1.98, 95% CI = 1.19-3.28, p = 0.009) and Both-aMCI (OR = 3.05, 95% CI = 1.97-4.71, p < 0.001) groups exhibited higher risks of progression to dementia. Memory recognition failure was associated with increased risk of progression to dementia only in the Visual-aMCI group, but not in the Verbal-aMCI and Both-aMCI groups. The Visual-aMCI without recognition failure group were subcategorized into aMCI with depression, small vessel disease, or accelerated aging, and these subgroups showed a variety of progression rates. Our findings underlined the importance of heterogeneous longitudinal outcomes of aMCI, especially Visual-aMCI, for designing and interpreting future treatment trials in aMCI.