[Time-sparing screening method for mild cognitive impairment and early Alzheimer's disease: Self- and family reports using the TMIG index of competence].

AIM: To verify the clinical utility of instrumental activities of daily life evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG-IC) as a screening tool for patients with early-phase cognitive impairment, including mild cognitive impairment (MCI) and early Alzheimer's disease (AD). METHODS: We recruited healthy subjects from our community-based cohort and consecutive subjects with MCI and AD from our clinic. The TMIG-IC was investigated in all participants and their family members. The total and subscale scores were compared among all groups. We then statistically determined the accuracy of the differentiation of MCI and AD. RESULTS: We registered 187 normal controls (NC), 39 participants with MCI, 50 AD patients with functional assessment staging (FAST) 4, and 19 AD patients with ≥5 FAST. The family-report score was significantly lower in MCI patients than in others, followed by AD patients. The total score was able to differentiate MCI and AD with a sensitivity of 85.7% and a specificity of 90.9% (area under the curve [AUC]=0.913). Differentiation of MCI alone had a low accuracy (AUC=0.787). However, the AUC was 0.847 when only the items with inconsistent responses between self and family reports were used as indices. CONCLUSIONS: The TMIG-IC is a useful tool for evaluating the severity of AD, including early AD. These findings suggest that family-report scores can differentiate MCI and AD from cognitive normal aging with a sufficient degree of accuracy. It was also suggested that inconsistencies between self and family reports were higher when differentiating MCI than the self- and family-reports.

[Study of encoding and storage in memorization among patients with Alzheimer's disease].

AIM: Memorization comprises three stages: encoding, storage, and retrieval. Using neuropsychological tests, we investigated the stage at which encoding and storage are retained in Alzheimer's disease (AD) patients with progressive memory disorder. METHODS: The target patients were an amnestic mild cognitive impairment (MCI) group (21 cases) and FAST 4 (37 cases), 5 (10 cases), and 6 (4 cases) AD groups. The neuropsychological tests performed were the Rivermead behavioral memory test and Wechsler memory scale-revised. These were carried out in the MCI group as well as in each AD stage group. We investigated the delayed recall (free recall and cued recall) based on the disease stage and raw score of the sub-items in delayed recognition. RESULTS: The MCI group had 48% (median 0 point) correct respondents (providing ≥1 correct answer) for free recall, whereas FAST 4 and 5 groups had ≤14% correct respondents. In the verbal paired associates II evaluated in cued recall, the MCI group had 90% correct respondents, and the FAST 4, 5, and 6 groups had rates of 51%, 60%, and 50%, respectively. For the pictures and photos in the delayed recognition tasks, there were no significant differences in the percentage of correct respondents between the MCI group (100%) and the FAST 4 and 5 groups (70%-90%). CONCLUSIONS: Given that retrieval is impossible if encoding and storage are impaired, we inferred that the encoding and retrieval abilities were retained even in moderately advanced AD.

[Development of a novel one-phrase screening test for early Alzheimer disease].

AIM: "Saving appearances behavior", pretending to know the correct answer, or a reply of deceptive replies, are often found in the reply of patients with dementia. We have already found that we can classify the answers to "what is the latest news on TV or newspapers?" into 4 types, including saving appearances answer. The purpose of the present study is to develop a simple clinical diagnostic method based on the answers to "what is the latest news on TV or newspapers?" for differentiating patients with Alzheimer's disease (AD) from those with mild cognitive impairment (MCI), and to test the validity, sensitivity and specificity of the method. METHODS: We recruited 133 consecutive outpatients with AD, 116 with MCI, and 54 normal cognitive aging controls (NC). Mini-Mental State Examination (MMSE) was performed for all of the subjects. Severity of memory disturbance was rated 0 (none) to 3 (severe) according to the results of the 3-object recall portion of the MMSE questionnaire. RESULTS: Only 20% of AD and 32% of MCI responded correctly about the recent news while 96% of NC responded correctly. Among patients with AD and MCI, one third of them showed "saving appearance behavior". Taking the result of the memory disturbance according to the MMSE in consideration, the present study indicates that the AD patients can be distinguished from MCI and NC with high sensitivity (98%) and high specificity (94%) using this simple, one-phrase question. CONCLUSIONS: "What is the latest news on TV or papers?" was highly effective in identifying AD and MCI. The present study suggests that the "saving appearances answer" is associated with the onset or awareness of memory impairment, the maintenance of the frontal lobe function and other characteristics of the patient.

Sporadic Triple A (Allgrove) Syndrome with Novel Tandem Mutations.

In triple A (Allgrove) syndrome, motor neuron disease is a co-morbid condition. We herein report a 38-year-old Japanese man with triple A (Allgrove) syndrome and novel tandem mutations: a novel c.881delT deletion mutation and c.835C>T localized to the AAAS gene. A nerve conduction study revealed marked axonal damage in several motor nerves. Tandem mutations in the AAAS gene may be involved in co-morbid motor neuron disease and aberrant electrophysiological findings.

Randomized double-blind placebo-controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease.

AIM: Yokukansan (YKS), a traditional herbal medicine, has been used to treat behavioral and psychological symptoms of dementia (BPSD). The present study is the first double-blind, randomized, placebo-controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimer's disease (AD). METHODS: A total of 22 sites consisting of clinics, hospitals and nursing homes participated. A total of 145 patients with AD were randomized. Active YKS (7.5 g/day) and placebo were supplied to 75 and 70 participants, respectively. The primary outcome measure was the 4-week change in total score of the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q), an instrument that evaluates BPSD. Secondary outcome measures included 12-week changes in NPI-Q scores, changes in NPI-Q subcategory scores and total scores of the Mini-Mental-State Examination. RESULTS: Four-week changes in NPI-Q total scores did not differ significantly between the treatment and placebo groups. There were also no significant differences between groups in 12-week changes in total NPI-Q scores, NPI-Q subcategory scores or total Mini-Mental-State Examination scores. However, a subgroup with fewer than 20 points on the Mini-Mental-State Examination at baseline showed a greater decrease in "agitation/aggression" score in the YKS group than in the placebo group (P = 0.007). No serious adverse effects were observed during the study. CONCLUSIONS: Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including "agitation/aggression" and "hallucinations" with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218.

Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging.

Alzheimer disease (AD) is pathologically characterized by cortical atrophy. Changes in the white matter and their relation to the pathogenesis of AD remain to be studied. To quantitatively investigate the integrity and organization of white matter fiber tracts in patients with AD, we used diffusion tensor (DT) imaging to study the diffusion anisotropy of white matter regions. DT imaging was performed using a 3.0 Tesla magnetic resonance scanner in ten probable AD patients with no or only mild changes in the white matter in T2 weighted magnetic resonance imagings and ten group-matched controls. The values of fractional anisotropy were significantly lower in the temporal subcortical white matter, posterior part of the corpus callosum, and anterior and posterior cingulate bundles in patients with AD compared with controls. Possible relationships of these selective impairments in the white matter with pathological changes in the posterior cerebral cortices and hippocampus were discussed.

Detection of active plaques in multiple sclerosis using susceptibility-weighted imaging: comparison with gadolinium-enhanced MR imaging.

PURPOSE: Susceptibility-weighted (SW) imaging is a magnetic resonance (MR) imaging technique reported effective in visualizing multiple sclerosis (MS) plaques, but its capacity to distinguish active plaques remains unclear. We evaluated active plaque detection by SW compared with contrast-enhanced MR imaging. METHODS: We prospectively examined 11 patients using a 3-tesla scanner. Two neuroradiologists independently evaluated signal changes of plaques and accompanying low signal rims in 74 plaques on various SW images (magnitude, phase, and minimum intensity projection [minIP]), and on contrast-enhanced T(1)-weighted images (T(1)WI). We correlated signal alterations on various SW images and contrast enhancement on T(1)WI using Fisher's exact test and calculated sensitivity and specificity for predicting gadolinium enhancement. RESULTS: Only changes in plaque signal on SW magnitude images correlated significantly with contrast enhancement of the plaques (P=0.008), and high signal intensity had 0.556 sensitivity and 0.787 specificity for predicting contrast-enhanced plaques. Furthermore, plaques with rims of low signal showed sensitivity of 0.296 and specificity of 0.957. CONCLUSIONS: Susceptibility-weighted magnitude, but not phase or minIP, images can predict MS plaques with contrast enhancement with high specificity.

Interleukin-2 production by peripheral blood mononuclear cells from patients with myasthenia gravis.

We examined interleukin-2 (IL-2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMs) from 75 untreated myasthenia gravis (MG) patients and 48 control patients. Patients with MG consisted of those with elevated PBM IL-2 production (>1,250 pg/ml; mean + 2SD of the controls) (n = 29, 39%) and those with normal PBM IL-2 production (<1,250 pg/ml) (n = 46, 61%). Significant characteristics of patients with elevated PBM IL-2 production included elevated serum levels of anti-acetylcholine receptor antibodies, severe generalized symptoms, thymic hyperplasia, and marked effects of thymectomy (p < 0.05). These findings suggest that elevated PBM IL-2 production can reflect functional abnormalities of T cells in some patients with MG, and that PBM IL-2 production should be considered as a candidate target of therapy.

Effects of FK506 on myasthenia gravis patients with high interleukin-2 productivity in peripheral blood mononuclear cells.

We compared the early effects of FK506 on clinical severity, interleukin-2 (IL-2) production by phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMs), and serum levels of acetylcholine receptor antibodies between myasthenia gravis (MG) patients with elevated (>1250 pg/ml, n = 9) or normal (<1250 pg/mL, n = 10) levels of PBM IL-2 production. Reduction in clinical severity and PBM IL-2 production were significantly greater in the patients with elevated IL-2 production than those with normal PBM IL-2 production in the first month of treatment.