Shigeto Nagao

Person-centered care and quality of life of patients with dementia in long-term care facilities.

Good quality of life (QOL) is an important goal of dementia care. However, there have been few studies on the relationship of care characteristics to QOL of dementia patients in long-term care facilities. We developed a questionnaire evaluating person-centered care and used it to assess person-centered care and QOL of elderly patients with dementia in both geriatric health service facilities (GHSF) and hospitals. In GHSF, person-centered care scores were not correlated with cognitive or activities of daily living (ADL) functions, but were significantly correlated with four subscale scores on a quality of life questionnaire for dementia (QOL-D) after controlling the effect of age, cognitive function, and ADL scores. In contrast, in hospitals, person-centered care scores were significantly correlated with cognitive and ADL function. We found quite different patterns in the relationship of person-centered care scores to clinical characteristics. Dementia care characteristics and QOL of dementia patients are significantly interrelated, especially in GHSF. Improvement of dementia care standards might affect the QOL of dementia patients. We should pay more attention to the quality of dementia care and QOL of dementia patients.

Trail making test B and brain perfusion imaging in mild cognitive impairment and mild Alzheimer's disease.

The trail making test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, there are few studies that elucidate the neural substrates of the TMT. The aim of the present study was to identify the brain regional perfusion patterns associated with performance on TMT part B (TMT-B) in patients with amnestic mild cognitive impairment (aMCI) or mild Alzheimers disease (AD). Twenty-one patients with good TMT-B scores and 21 age- and sex-matched patients with poor TMT-B scores were selected. All 42 subjects underwent brain single photon emission computed tomography (SPECT), and the SPECT images were analyzed by statistical parametric mapping. No significant differences between good- and poor-scoring groups were found with respect to years of education, Addenbrookes Cognitive Examination scores, and scores on TMT-A. Compared to patients with good scores on TMT-B, patients with poor scores showed significant hypoperfusion in the bilateral anterior cingulate extending to the posterior region on the right side, bilateral caudate nucleus and putamen, and bilateral thalamus. Analysis of 63 AD or aMCI subjects revealed significant correlation a between regional cerebral blood flow in the right cingulate cortex and TMT-B scores. Our results suggest that functional activity of the anterior cingulate, striatum and thalamus is closely related to performance time on TMT-B. The performance time on the TMT-B score might be a promising index of dysfunction of the anterior cingulate, striatum, and thalamus among patients with aMCI or mild AD.

Frontal assessment battery and brain perfusion imaging in Alzheimer's disease

BACKGROUND The frontal assessment battery (FAB) is reported to be a useful tool for assessing frontal dysfunction. However, the neural substrates involved in patients with Alzheimers disease (AD) remain to be elucidated. The aim of the present study was to identify the regional perfusion patterns of the brain associated with performance scores on the FAB of patients with AD using brain perfusion assessed by single photon emission computed tomography (SPECT). METHODS Twenty-four AD patients with high scores and 24 age- and sex-matched AD patients with low scores on the FAB were selected from 470 consecutive Japanese patients of the Memory Clinic of Okayama University Hospital. All 48 participants underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by statistical parametric mapping. RESULTS No significant differences were found between high and low FAB scoring groups with respect to Addenbrookes Cognitive Examination scores, Mini-Mental State Examination scores, or the depression score of the Neuropsychiatric Inventory subscale. Compared with patients with high scores on the FAB, AD patients with low scores showed significant hypoperfusion in the left middle frontal gyrus (MFG) and the right superior frontal gyrus (SFG) extending to the left SFG. CONCLUSION Our results suggest that functional activity of the SFG and MFG is closely related to the FAB score. The FAB might be a promising strategy to detect early stages of AD with low SFG and MFG function.

Depressive symptoms and regional cerebral blood flow in Alzheimer's disease

Depressive symptoms are common in patients with Alzheimers disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of depressive symptoms in AD, excluding the effect of apathy and anxiety. Seventy-nine consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. The level of depressive symptoms was evaluated using the depression domain of the Neuropsychiatric Inventory (NPI). The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. After removing the effects of age, anxiety and apathy scores of NPI, and five subscales of Addenbrookes Cognitive Examination-revised (ACE-R), correlation analysis of NPI depression scores showed a significant cluster of voxels in the left middle frontal gyrus (Brodmann area 9), similar to the areas in the simple correlation analysis. The dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD, and the area on the left side especially may be closely related to the depressive symptoms revealed by NPI.

Accelerated Tau Aggregation, Apoptosis and Neurological Dysfunction Caused by Chronic Oral Administration of Aluminum in a Mouse Model of Tauopathies

To clarify whether long‐term oral ingestion of aluminum (Al) can increase tau aggregation in mammals, we examined the effects of oral Al administration on tau accumulation, apoptosis in the central nervous system (CNS) and motor function using tau transgenic (Tg) mice that show very slowly progressive tau accumulation. Al‐treated tau Tg mice had almost twice as many tau‐positive inclusions in the spinal cord as tau Tg mice without Al treatment at 12 months of age, a difference that reached statistical significance, and the development of pretangle‐like tau aggregates in the brain was also significantly advanced from 9 months. Al exposure did not induce any tau pathology in wild‐type (WT) mice. Apoptosis was observed in the hippocampus in Al‐treated tau Tg mice, but was virtually absent in the other experimental groups. Motor function as assessed by the tail suspension test was most severely impaired in Al‐treated tau Tg mice. Given our results, chronic oral ingestion of Al may more strongly promote tau aggregation, apoptosis and neurological dysfunction if individuals already had a pathological process causing tau aggregation. These findings may also implicate chronic Al neurotoxicity in humans, who frequently have had mild tau pathology from a young age.

Burden of caregivers for patients with mild cognitive impairment in Japan.

BACKGROUND Caregivers of patients with mild cognitive impairment (MCI) already experience a need for increased services comparable to that of individuals caring for Alzheimers disease patients. However, there have been only a few studies on the MCI caregiver burden. In this study, we examined MCI caregiver burden in a larger number of consecutive outpatients in Japan. METHODS One hundred and four consecutive caregivers of people with MCI participated in this study. The caregiver burden was evaluated by the short version of the Japanese version of the Zarit Burden Interview (sZBI). RESULTS About 20% of the caregivers reported a clinically significant burden. The multiple linear regression analysis showed that the caregiver burden was significantly associated with neurobehavioral symptoms (p < 0.001) and memory problems (p = 0.022) of the patient. CONCLUSIONS The caregiver burden of MCI patients should be given more attention. The management of neurobehavioral symptoms may be important to reduce the burden on caregivers of MCI patients.

Progressive supranuclear palsy presenting as primary lateral sclerosis but lacking parkinsonism, gaze palsy, aphasia, or dementia.

We report an autopsy case of progressive supranuclear palsy (PSP) that clinically showed only slowly progressive and symmetric upper motor neuron syndrome over a disease course of 12 years. A female patient initially exhibited dysarthria at the age of 65, followed by gait disturbance and dysphagia. Neurological examination at age 67 disclosed pseudobulbar palsy, spastic gait, hyperreflexia, and presence of bilateral Hoffmann and Babinski signs. However, muscle atrophy, weakness, evidence of denervation on electromyography, vertical gaze palsy, parkinsonism, gait freezing, aphasia, speech apraxia, or dementia was not noted throughout the course. She was clinically diagnosed as having motor neuron disease consistent with so-called primary lateral sclerosis. Pathological examination disclosed histopathological features of PSP, including argyrophilic and tau-positive tufted astrocytes, neurofibrillary tangles, coiled bodies, and thread-like processes in the motor cortex and superior frontal gyrus, and to a lesser degree, in the basal ganglia and brain stem nuclei. In addition, severe fibrillary gliosis was noted in the precentral gyrus and corticospinal tract, being consistent with upper motor neuron syndrome observed in this case. No TAR-DNA binding protein 43-positive lesion, FUS pathology, Bunina body, or Lewy body-like hyaline inclusion was noted in the motor cortex or lower motor neurons. These findings suggest that when tau pathology is prominent in the motor cortex but is minimal in the basal ganglia and brain stem nuclei, a PSP case can lack all classic clinical features of PSP and show only slowly progressive upper motor syndrome, consistent with clinical picture of primary lateral sclerosis.

Subjective depressive mood and regional cerebral blood flow in mild Alzheimer's disease

BACKGROUND Depressive symptoms are common in patients with Alzheimers disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of subjective depressive symptoms in AD. METHODS Seventy-six consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. Subjective depressive symptoms were evaluated using the short version of the Geriatric Depression Scale (GDS). All patients underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by the Statistical Parametric Mapping 8 program. RESULTS No significant differences between groups with high and low GDS scores were found with respect to age, sex, years of education, and revised Addenbrookes Cognitive Examination scores. Compared to patients with low scores on GDS, patients with high scores showed significant hypoperfusion in the left inferior frontal region. CONCLUSIONS The left inferior frontal region may be significantly involved in the pathogenesis of subjective depressive symptoms in AD. Subjective and objective depressive symptoms may have somewhat different neural substrates in AD.

The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies in Subcortical Nuclei and Progression of Argyrophilic Grain Disease

Progressive supranuclear palsy (PSP) cases frequently have argyrophilic grain disease (AGD). However, the PSP‐like tau pathology in AGD cases has not been fully clarified. To address this, we examined tau pathologies in the subcortical nuclei and frontal cortex in 19 AGD cases that did not meet the pathological criteria of PSP or corticobasal degeneration, nine PSP cases and 20 Braak NFT stage‐matched controls. Of the 19 AGD cases, five (26.3%) had a few Gallyas‐positive tau‐positive tufted astrocytes (TAs) and Gallyas‐negative tau‐positive TA‐like astrocytic inclusions (TAIs), and six (31.6%) had only TAIs in the striatum and/or frontal cortex. Subcortical tau pathology was sequentially and significantly greater in AGD cases lacking these tau‐positive astrocytic lesions, AGD cases having them, and PSP cases than in controls. There was a significant correlation between three histologic factors, including the AGD stage and the quantities of subcortical neuronal and astrocytic tau pathologies. Tau immunoblotting demonstrated 68‐ and 64‐kDa bands and 33‐kDa low‐molecular mass tau fragments in PSP cases, and although with lesser intensity, in AGD cases with and without TAs and TAIs also. Given these findings, the progression of AGD may be associated with development of the neuronal and astrocytic tau pathologies characteristic of PSP.

Trail Making Test Part A and Brain Perfusion Imaging in Mild Alzheimer's Disease

Background/Aims: The Trail Making Test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, there are few studies that elucidate the neural substrates of the TMT. The aim of the present study was to identify the regional perfusion patterns of the brain associated with performance on the TMT part A (TMT-A) in patients with Alzheimers disease (AD). Methods: Eighteen AD patients with poor performance on the TMT-A and 36 age- and sex-matched AD patients with good performance were selected. All subjects underwent brain single photon emission computed tomography. Results: No significant differences between the good and poor performance groups were found with respect to years of education and revised Addenbrookes Cognitive Examination scores. However, higher z-scores for hypoperfusion in the bilateral superior parietal lobule were observed in the group that scored poorly on the TMT-A compared with the good performance group. Conclusion: Our results suggest that functional activity of the bilateral superior parietal lobules is closely related to performance time on the TMT-A. Thus, the performance time on the TMT-A might be a promising index of dysfunction of the superior parietal area among mild AD patients.