Free water in gray matter linked to gut microbiota changes with decreased butyrate producers in Alzheimer's disease and mild cognitive impairment.

Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and has been used to study neuroinflammation across several neurological diseases including AD. Recently, the role of gut microbiota has been implicated in the pathogenesis of AD. The relationship between FW imaging and gut microbiota was examined in patients with AD and MCI. Fifty-six participants underwent neuropsychological assessments, FW imaging, and gut microbiota analysis targeting the bacterial 16S rRNA gene. They were categorized into the cognitively normal control (NC) (n = 19), MCI (n = 19), and AD (n = 18) groups according to the neuropsychological assessments. The correlations of FW values, neuropsychological assessment scores, and the relative abundance of gut microbiota were analyzed. FW was higher in several white matter tracts and in gray matter regions, predominantly the frontal, temporal, limbic and paralimbic regions in the AD/MCI group than in the NC group. In the AD/MCI group, higher FW values in the temporal (superior temporal and temporal pole), limbic and paralimbic (insula, hippocampus and amygdala) regions were the most associated with worse neuropsychological assessment scores. In the AD/MCI group, FW values in these regions were negatively correlated with the relative abundances of butyrate-producing genera Anaerostipes, Lachnospiraceae UCG-004, and [Ruminococcus] gnavus group, which showed a significant decreasing trend in the order of the NC, MCI, and AD groups. The present study showed that increased FW in the gray matter regions related to cognitive impairment was associated with low abundances of butyrate producers in the AD/MCI group. These findings suggest an association between neuroinflammation and decreased levels of the short-chain fatty acid butyrate that is one of the major gut microbial metabolites having a potentially beneficial role in brain homeostasis.

Safety and pharmacokinetics of bapineuzumab in a single ascending-dose study in Japanese patients with mild to moderate Alzheimer's disease.

AIM: To evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimer's disease. METHODS: Participants received either a placebo (n = 8), or bapineuzumab 0.15 (n = 6), 0.5 (n = 6), 1.0 (n = 6) or 2.0 (n = 6) mg/kg. Serum concentrations of bapineuzumab, antibapineuzumab antibody and total plasma ß-amyloidx-40 were assayed. RESULTS: Adverse events for bapineuzumab and placebo groups were 71% and 88%, respectively. Treatment-emergent adverse events (cataract, injection site hemorrhage, nasopharyngitis, pneumonia and muscle twitching) reported for ≥2 participants were mild or moderate in severity and unrelated to bapineuzumab dose. No deaths, serious adverse events or withdrawals were reported. Mean peak concentration for bapineuzumab increased with dose, from 3.3 ± 0.9 µg/mL with the 0.15 mg/kg dose to 61.0 ± 32.8 µg/mL with 2.0 mg/kg. Mean bapineuzumab exposure (area under the curve from time 0 to last measurable concentration; µg·h/mL) increased in a linear manner with increasing dose (mean 1260 for 0.15 mg/kg, 4264 for 0.5 mg/kg, 7818 for 1.0 mg/kg, 15 313 for 2.0 mg/kg). Mean half-life ranged from 15 to 28 days, and clearance was similar across dose groups (range 0.12-0.17 mL/h/kg). CONCLUSIONS: Plasma ß-amyloidx-40 levels increased with increasing doses of bapineuzumab. Bapineuzumab was safe and well tolerated at all doses in Japanese patients with mild to moderate Alzheimer's disease. Geriatr Gerontol Int 2016; 16: 644-650.

Quantitative evaluation of electroconvulsive therapy for Parkinson's disease with refractory psychiatric symptoms.

Patients with advanced-stage Parkinson's disease (PD) occasionally experience refractory depression or catatonic stupor. Electroconvulsive therapy (ECT) has been reported as a successful procedure for both severe psychosis and motor symptoms in patients with PD. Four patients with PD who were receiving ECT were quantitatively evaluated using the Unified PD Rating scale part III, Hoehn and Yahr scale, Barthel index, Neuropsychiatric Inventory, mini-mental state examination, Revised Hasegawa's Dementia scale, Beck's Depression Inventory, and Hamilton Rating Scale for Depression-17. We adopted the "half-age" method, which is an age-based stimulus-dosing method. The patients showed improvement in symptoms of psychosis and motor symptoms without any adverse effects. The interval of improvement after ECT varied among patients. Of note, a decrease in psychiatric symptoms successfully alleviated the burden of caregivers. ECT may be useful to treat parkinsonism with refractory psychosis, major depression, or catatonic stupor, within the limitations of the patients enrolled.

Recurrent cholecystitis in an elderly mentally retarded patient with pica.

The case of a 64-year-old patient with pica and severe mental retardation who was admitted to our hospital for treatment of recurrent cholecystitis is reported. Abdominal ultrasound showed sludge in the gallbladder, but no stones. Abdominal CT revealed a foreign body in the duodenum resembling a suction cup of the type commonly used in kitchens and bathrooms. The object could not be removed because it was deeply embedded in the hypertrophic intestinal mucosa. A nasogastric tube was inserted for feeding, since the object impeded the passage of solid foods. The patient's fever and abdominal pain subsequently resolved, and laboratory data improved. The indwelling feeding tube prevented recurrence of cholecystitis. Since pica is common not only in patients with mental retardation but also in dementia patients, the present case may also relate to the treatment of acute abdominal conditions in dementia patients.

Pulmonary embolism from persistent dilatation of the bladder secondary to anticholinergic side effects.

OBJECTIVE: To discuss the risk that bladder distention resulting from anticholinergic side effects of antipsychotics can cause iliac vein compression syndrome (IVCS) and subsequent pulmonary embolism (PE). METHOD: Case report, review of the literature and discussion. RESULTS: We report the case of a 65-year-old man with depression who experienced PE associated with IVCS due to a distended urinary bladder resulting from anticholinergic side effects. PE disappeared after conservative therapy with heparin followed by warfarin. CONCLUSION: When drugs with anticholinergic effects are given to immobilized patients such as those with severe depression, close observation including monitoring of urine volume is needed to prevent IVCS caused by drug-induced urinary retention, and subsequent PE.

Maximal response to electroconvulsive therapy for the treatment of catatonic symptoms.

OBJECTIVES: Because the number of medical lawsuits has recently increased in Japan, doses of medication above the upper limits have recently been avoided, even when treating catatonic patients. We treated catatonic symptoms with drugs within the upper limit of dosage and electroconvulsive therapy (ECT) to determine the maximal response. METHODS: We examined 50 consecutive patients with catatonic symptoms admitted to a university hospital during a 32-month period who were treated with either drugs within the upper limit or ECT. RESULTS: Response rates were as follows: ECT, 100%; chlorpromazine, 68%; risperidone, 26%; haloperidol, 16%; and benzodiazepines, 2%. CONCLUSIONS: The findings indicated that ECT is the treatment of choice for catatonic symptoms.

Prolonged and fluctuating giant T-wave inversion after electroconvulsive therapy.

A 76-year-old woman was scheduled to receive 8 treatments of electroconvulsive therapy (ECT) for severe depression. Although she experienced no adverse consequences in the first 2 treatments, giant T-wave inversion ensued from the third treatment despite no change in anesthesia or technical parameters of ECT. T-wave inversion appeared to have almost disappeared 8 days after the third ECT, but reappeared at 3 weeks after treatment during severe pain from gallbladder stone. T-wave inversion lasted for 4 months with gradual attenuation. Exaggerated sympathetic stimulation associated with ECT as physical and emotional stressors might have played a role in the appearance of T-wave inversion similar to catecholamine-induced cardiomyopathy. Furthermore, reappearance of T-wave inversion may have been involved in additive effects of pain from gallbladder stone on vulnerability due to a catecholamine-induced cardiomyopathy-like condition.

A quantitative near-infrared spectroscopy study: a decrease in cerebral hemoglobin oxygenation in Alzheimer's disease and mild cognitive impairment.

A newly developed quantitative near-infrared spectroscopy (NIRS) system was used to measure changes in cortical hemoglobin oxygenation during the Verbal Fluency Task in 32 healthy controls, 15 subjects with mild cognitive impairment (MCI), and 15 patients with Alzheimer's disease (AD). The amplitude of changes in the waveform, which was quantitatively calculated by a signal processing method, was significantly lower in the frontal, and the bilateral parietal areas in the AD group, whereas that in the MCI group was significantly lower only in the right parietal area. The NIRS system may be a potential tool for the primary screening of AD.