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Motion perceptual deficits are common in Alzheimer's disease (AD). Although the posterior parietal cortex is thought to play a critical role in these deficits, it is currently unclear whether the primary visual cortex (V1) contributes to these deficits in AD. To elucidate this issue, we investigated the net activity or connectivity within V1 in 17 amnestic mild cognitive impairment (aMCI) patients, 17 AD patients and 17 normal controls (NC) using functional magnetic resonance imaging (fMRI). fMRI was recorded under two conditions: visual motion stimulation and resting-state. The net activity or connectivity within V1 extracted by independent component analysis (ICA) was significantly increased during visual motion stimuli compared with that of the resting-state condition in NC, but not in aMCI or AD patients. These findings suggest the alteration of the net activity or connectivity within V1, which may contribute to the previously reported motion perceptual deficits in aMCI and AD. Therefore, the decreased net V1 activity measured as the strength of the ICA component may provide a new disease biomarker for early detection of AD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Visuospatial dysfunction including defects in motion perception in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are clues to search for potential in vivo biomarkers. In this review, we focus on the clinical relevance of non-invasive neurophysiological findings in event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in AD and MCI. We first summarize the current concept of the parallel visual pathways in primates and humans. Next, we outline the results of previous electrophysiological and fMRI studies on visual function in AD and MCI. Finally, we present the recent findings of our systematic ERP and fMRI approach to visual perception in AD and MCI. Our overview strongly indicates that visual impairments in patients with AD and MCI are mainly caused by dysfunction in higher-level parallel visual pathways. In particular, a deficit in ventro-dorsal stream function related to optic flow perception is responsible for the earliest and most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI measurements for visual perception can be used as in vivo biomarkers for early functional brain changes in MCI and AD patients.

Background: Although dementia has a great impact on public health, there are few reports on dementia incidence and risk factors for Asian populations., Objectives: To determine incidence and risk factors of dementia, Alzheimer disease (AD), and vascular dementia (VaD) among Japanese women., Methods: Between 1992 and 1996, 1637 non-demented women aged > or =60 years were followed for an average of 5.9 years in RERF's Adult Health Study. Dementia diagnoses were made during biennial health examinations using a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS-ADRDA for AD, and NINDS-AIREN for VaD. Potential risk factors were analyzed using Poisson regression analysis., Results: 161 cases of dementia (109 of AD and 56 of VaD, based on individual criteria) were newly diagnosed. Incidence increased dramatically with age, especially for AD. Probable AD decreased with increasing education level. Probable VaD was significantly associated with hypertension and stroke. Age at menopause did not show any effect on dementia. All dementia and probable AD were significantly associated with grip strength., Conclusions: AD is predominant in dementia incidence among Japanese women. Modification of stroke risk factors and improvement of physical fitness may help prevent dementia.

Objective: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population., Methods: 2,286 dementia-free subjects, aged > or =60 years, were followed for 5.9 years through biennial two-phase examinations., Results: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26)., Conclusion: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype., ((c) 2008 S. Karger AG, Basel)

Objectives: To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimer's disease or vascular dementia., Design: A prevalence study within a longitudinal cohort study., Setting: The original Adult Health Study (AHS) cohort consisted of atomic-bomb survivors and their controls selected from residents in Hiroshima and Nagasaki using the 1950 national census supplementary schedules and the Atomic Bomb Survivors Survey. Since 1958, the AHS subjects have been followed through biennial medical examinations., Participants: Subjects were 637 men and 1585 women aged 60 years or older in the AHS cohort. Forty-eight subjects resided in hospitals and institutions., Measurements: In addition to the biennial medical examinations ongoing since 1958, a screening test for cognitive impairment (CASI) was conducted by trained nurses between September 1992 and September 1996. The prevalence of dementia and its subtypes was assessed in 343 subjects suspected to have dementia and in 272 subjects with high CASI scores who were selected randomly., Results: The prevalence of dementia based on DSM III/R criteria, using neurological examination, the IQCODE, and CDR > or = 1, was 7.2%. The prevalence of Alzheimer's disease was 2.0% in men and 3.8% in women, and the prevalence of vascular dementia was 2.0% in men and 1.8% in women. The relationship of risk factors to Alzheimer's disease or vascular dementia was investigated by the multivariate logistic linear regression analysis. Odds ratios of Alzheimer's disease for age (in 10-year increments), attained education (in 3-year increments), history of head trauma, and history of cancer are 6.3, 0.6, 7.4, and 0.3, respectively. Odds ratios of vascular dementia for age, history of stroke, and history of hypertension are 2.0, 35.7, and 4.0, respectively. Neither type of dementia showed any significant effect of sex or radiation exposure., Conclusion: This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan.

In brains from Alzheimer's disease patients, a high activity of acetylcholinesterase (AChE) was detected in the senile plaque-rich fraction and its isozyme pattern was mainly type A, containing a collagen-like tail. AChE inhibitors, including physostigmine, E-2020, amiridin, tetrahydroaminoacridine (THA) and Nicergoline had a poor effect on AChE present in the senile plaque-rich fraction isolated from Alzheimer brain than that either in the soluble fraction of Alzheimer brain or in the control brain. However, AChE purified from rat skeletal muscle (type A) was significantly more susceptible to AChE inhibitors than that purified from rat brain (G4 form) or from human erythrocytes (G2 form). E-2020 inhibited all 3 types of isozymes more effectively than physostigmine, amiridine, Nicergoline or THA. The inhibitory effect of AChE inhibitors on AChE solubilized from senile plaque was also small as compared with AChE in normal human brain, rat brain, human erythrocytes or rat skeletal muscle. These results suggest that the characteristics of AChE present in senile plaques are abnormal or different from that in normal brain or skeletal muscle. As AChE in the Alzheimer brain seems to contain a higher degree of glycosylation, the hydrophobic property of anomalous AChE may serve a seed of amyloid fibril in senile plaques.

Fursultiamine (TTFD), a derivative of thiamine, at an oral dose of 100 mg/day had a mild beneficial effect in patients with Alzheimer's disease in a 12-week open trial. The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function. Only mildly impaired subjects showed cognitive improvement. Alzheimer patients' blood levels of thiamine before the trial were within the normal range. No adverse reactions were observed and all patients tolerated the trial well. TTFD could afford an alternate treatment to large doses of thiamine hydrochloride in Alzheimer patients. However, further investigations of the therapeutic implications of thiamine and its possible etiologic clues to Alzheimer's disease are necessary.

We studied auditory event-related potentials (ERPs) in 40 patients with dementia of the Alzheimer type (DAT). Peak latencies and amplitudes of N100, P200 and P300 components were measured. To study the possible relationships between the ERPs and monoaminergic neurotransmitter functions, CSF neurotransmitter metabolites were also analyzed. In patients with DAT, the P300 amplitude was significantly reduced and the P300 latency was prolonged. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were decreased. The P300 amplitude was significantly correlated with the 5-HIAA concentration. There were no correlations between the P300 components and the HVA concentration. These findings suggest that the serotonergic system modulates the P300 component of ERPs in patients with DAT.