[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.

Detection of changes in the locus coeruleus in patients with mild cognitive impairment and Alzheimer's disease: high-resolution fast spin-echo T1-weighted imaging.

AIM: Neuronal degeneration in the locus coeruleus occurs in the early phase of Alzheimer's disease, similar to mild cognitive impairment. The locus coeruleus produces norepinephrine, a deficiency of which causes both memory disturbance and psychological symptoms. Thus, we evaluated signal alterations in the locus coeruleus of patients with Alzheimer's disease and mild cognitive impairment using a high-resolution fast spin-echo T1-weighted imaging. METHODS: A total of 22 patients with Alzheimer's disease, 47 patients with mild cognitive impairment and 26 healthy controls were prospectively examined by high-resolution fast spin-echo T1-weighted imaging at 3 Tesla. Signal intensities in the locus coeruleus were manually measured and expressed relative to those in the adjacent white matter structures as contrast ratios. RESULTS: Locus coeruleus contrast ratios were significantly reduced in patient groups with Alzheimer's disease, mild cognitive impairment that converted to Alzheimer's disease and mild cognitive impairment that did not convert to Alzheimer's disease (1.80-16.09% [median, 9.30%], 3.45-14.84% [median 6.87%] and 3.01-19.19% [median 7.72%], respectively) compared with the healthy control group (6.24-20.94% [median 14.35%]; P < 0.0001). The sensitivity and specificity for discriminating these diseases were 85.0% and 69.2%, respectively, which suggests that this measurement can be carried out reliably. There was no significant difference in the locus coeruleus contrast ratios among the Alzheimer's disease, mild cognitive impairment-converted and mild cognitive impairment-non-converted groups. CONCLUSIONS: High-resolution fast spin-echo T1-weighted imaging can show signal attenuation in the locus coeruleus of patients with Alzheimer's disease or with mild cognitive impairment whose pathology may or may not eventually convert to Alzheimer's disease.

[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.

High-dose argatroban therapy for stroke: novel treatment for delayed treatment and the recanalization mechanism.

BACKGROUND: There has been little effective treatment in patients with cerebral infarction at >24 hours after onset. We assessed the effects of high-dose argatroban therapy in delayed administration, and investigated the mechanism based on our clinical findings. METHODS: Argatroban 30 mg was first administered for 15 minutes intravenously, and then 90 mg for 60 minutes followed by 60 mg for 60 minutes were infused continuously. The change of vascular obstruction caused by the treatment was assessed with magnetic resonance angiography. RESULTS: In 4 patients studied, high-dose argatroban resulted in 100% recanalization of occluded vessels (5/5), even though argatroban was administrated >24 hours after onset. On the other hand, when an inadequate dose of argatroban was administered, a hemorrhage was identified. This supports our hypothesis that high-dose argatroban promotes recanalization by deactivating thrombin and exerting an anticoagulant effect on the vascular endothelium. CONCLUSIONS: High-dose argatroban is an effective treatment for cerebral infarction and offers a novel therapeutic approach for delayed hospitalized patients at >24 hours after onset. Additional studies are necessary to identify the cellular and molecular mechanisms and determine the adequate dose in order to reduce risks of complication.