Junichi Ishizaki

Prevalence and Cognitive Performances of Clinical Dementia Rating 0.5 and Mild Cognitive Impairment in Japan. The Tajiri Project

The borderline zone condition between normal aging and dementia is a major issue of concern. Although the term mild cognitive impairment (MCI) is popular, its prevalence and neuropsychological features have not been fully investigated. We investigated the prevalence and neuropsychological features for Clinical Dementia Rating (CDR) 0.5 and MCI. For normal aging, the effects of age and educational level on cognitive performance were examined. We examined 1501 older residents (46.8%) in Tajiri 65 years of age and older. They performed the Cognitive Abilities Screening Instrument (CASI). Depressive scores and subjective memory complaints were also evaluated. There was no age effect but an educational effect on cognitive performance in healthy adults. We found the overall prevalence of CDR 0.5 to be 30.2%, whereas that of MCI was only 4.9%. All CASI domains were deteriorated except for long-term memory and visual construction in the CDR 0.5 participants compared with healthy adults, suggesting that CDR 0.5 is similar to very mild Alzheimer disease. Memory complaints’ data suggested that it would be better to exclude memory complaints from the MCI criteria. We considered that the concept of CDR 0.5 would be more applicable to community residents rather than that of the MCI.

Cognitive function and frontal lobe atrophy in normal elderly adults: Implications for dementia not as aging‐related disorders and the reserve hypothesis

Abstract We examined the relations between cognitive function and age and education in the normal elderly population. As per the community‐based stroke, dementia, and bed confinement pre‐vention in the town of Tajiri, neuropsychological assessments, including the Cognitive Ability Screening Instrument (CASI), were performed for 99 randomly selected normal elderly subjects. We assessed the frontal function (working memory, word fluency, Trail‐Making Tests, CASI subitems of list‐generating fluency, attention, and concentration/mental manipulation), language function (proverbs, CASI subitem language), non‐language function (the digit symbol test of the Wechsler Adult Intelligence Scale‐Revised (WAIS‐R), CASI subitem visual construction), memory (Alzheimers Disease Assessment Scale recall/recognition, story recall, CASI subitems short and long‐term memory, the Rey‐Osterrieth Complex Figure Test), and the global function (CASI subitems orientation and abstraction and judgment). We found that the only test affected by age was the digit symbol test of the WAIS‐R. The effects of education were distributed among various tests. There was a significant correlation between age and the frontal lobe atrophy in the lower educated group. The present findings suggest that cognitive function is spared by the aging process itself and dementia should be considered as age‐related, not aging‐related disorders, and that education might have a protective effect on cognitive change, supporting the reserve hypothesis.

Non-verbal learning is impaired in very mild Alzheimer's disease (CDR 0.5): normative data from the learning version of the Rey-Osterrieth Complex Figure Test.

Abstract  Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia. Although there have been some studies on the role of verbal memory in learning ability, there have been no reports on the part played by visual memory. In the present study, the Rey–Osterrieth Complex Figure Test (RCFT) was given to healthy subjects and to those with MCI to determine if visual memory was maintained in these two groups. Additionally, normative data from the learning version of the RCFT for Japanese subjects were examined, for purpose of reference. The participants consisted of 381 clinical dementia rating (CDR) 0 subjects and 137 CDR 0.5 subjects who could perform the full set of RCFT tasks. The CDR 0 group had significantly higher scores than the CDR 0.5 group in all trials. The CDR 0 participants also showed a significant step‐by‐step learning effect, while the CDR 0.5 participants did not show a significant learning effect. These results suggest that the CDR 0 participants maintained intact learning abilities of encoding and retrieval, while the CDR 0.5 participants did not do so; but further studies will be needed to clarify these findings.

Discrepancy Between Mental Rotation and Perspective-Taking Abilities in Normal Aging Assessed by Piaget's Three-Mountain Task

In a cross-sectional study, we examined age-related differences in visuo-spatial ability associated with image rotation, using two variants of Piagets ‘Three-Mountain Task.’ The object-mental rotation (OMR) task detects the ability to mentally rotate an image, whereas the subject-mental rotation (SMR) task reveals the ability to mentally change ones perspective. A group of 33 young adults, 26 middle-aged adults, and 31 elderly normal adults were studied. Both tasks revealed age-related differences in performance but a larger difference between middle-aged and elderly group was observed for SMR than OMR performance. Age-related increases in the ‘egocentric’ type of error were found only on the SMR task. The results suggest that the ability to mentally change ones perspective declines with age, perhaps more than the ability to mentally rotate objects.

Five-year retrospective changes in hippocampal atrophy and cognitive screening test performances in very mild Alzheimer's disease: the Tajiri Project

Abstract. The medial temporal lobe, especially the hippocampus, is important for normal cognitive function, especially for memory, and is the region with the earliest and most extensive pathological changes in Alzheimers disease (AD). We investigated the atrophic changes of the hippocampus over a 5-year period and its relation to cognitive screening test performances in normal elderly subjects, those with very mild AD, and patients with AD. Fifty-seven elderly subjects without a moderate or greater degree of cerebrovascular disease as shown by MRI were randomly selected from the town of Tajiri. Thirty-three subjects with a clinical dementia rating (CDR) of 0 (normal), 18 CDR-0.5 (very mild AD) subjects, and six CDR-1&2 (AD) subjects underwent MRI and the Mini Mental State Examination (MMSE) twice during the period. Retrospective changes in the hippocampal width and the MMSE scores were evaluated. There were significant CDR group effects for the changes in the mean bilateral hippocampal widths and the MMSE scores. Normal subjects did not show cognitive decline, although there was a slight tendency for hippocampal atrophy. A significant and meaningful Spearmans correlation was noted between left hippocampal atrophy and the MMSE scores over the 5-year period for the CDR-0.5 group. These CDR-0.5 subjects met the MCI (mild cognitive impairment) criteria as proposed by the consensus paper. Findings suggested that normal elderly subjects maintain a high level of cognitive functions for at least 5 years, although hippocampal atrophy might occur. Atrophic change of the left hippocampus might be a good marker of the very early stage of AD.

Therapeutic psychosocial intervention for elderly subjects with very mild Alzheimer disease in a community: The Tajiri Project

Elderly subjects with mild memory impairment but not apparent dementia are the focus of early intervention trials. To examine the effects of structural psychosocial intervention for elderly subjects with very mild Alzheimer disease, i.e., Clinical Dementia Rating 0.5. The design is a prospective study. The experimental group (14 Clinical Dementia Rating 0.5 subjects) and the control group (11 Clinical Dementia Rating 0.5 subjects) were studied. Subjects with cerebrovascular disease as shown by magnetic resonance imaging were excluded. The experimental group participated in activities in a day-care-like setting once a week over a period of 6 months, whereas the control group did not. Each group was reevaluated after approximately 9 months. The effects of intervention were evaluated by cognitive tests, affective scales, a global clinical measure, an observation scale in the sessions, and a projective test. The experimental group showed a significant improvement on the word fluency test, whereas the control group showed a significant decline on the Mini-Mental State Examination, the digit span, and the Trail Making-A test. The experimental group revealed significantly higher levels on the Mini-Mental State Examination and the digit span compared with the control group after the 6-month intervention. A significant improvement was found for the global clinical measure, the observation scale, and the projective test in the experimental group after the intervention. After controlling the potential confounders (age, educational level, baseline cognitive, and affective status) in a multiple regression analysis, the same results were found. We considered that psychosocial intervention had beneficial effects for subjects with very mild Alzheimer disease.

Corpus Callosum Atrophy, White Matter Lesions, and Frontal Executive Dysfunction in Normal Aging and Alzheimer's Disease. A Community-Based Study: The Tajiri Project

BACKGROUND AND OBJECTIVES Cerebral MRIs of normal aging and Alzheimers disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship or the relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WMH, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. METHOD We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. RESULTS Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency test in the HC group. CONCLUSION In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical ischemic conditions.

Language deterioration in four Japanese–Portuguese bilingual patients with Alzheimer's disease: a trans‐cultural study of Japanese elderly immigrants in Brazil

Background:  Bilingualism is an area of linguistics that has been investigated in aphasic patients. However, bilingualism and Alzheimers disease (AD) have not been fully investigated despite the fact that language impairment is a frequent symptom of AD. Brazil has the greatest number of Japanese immigrants and, consequently, there are many bilingual people who are fluent in both Japanese and Portuguese in Brazil.

Executive dysfunction can explain word‐list learning disability in very mild Alzheimer's disease: The Tajiri Project

Abstract  Elderly people with questionable dementia (i.e. a Clinical Dementia Rating (CDR) of 0.5) have been focused on as representing the borderline zone condition between healthy people and dementia patients. Many of them are known to have pathologic traits of very mild Alzheimers disease (AD). Although they present mild memory disorder, the underlying mechanism has not been fully investigated. Herein is reported the mechanism of learning disability in very mild AD. Eighty‐six CDR 0.5 participants and 101 age‐ and education‐matched healthy controls (CDR 0) were randomly selected from a community in the town of Tajiri, Miyagi Prefecture. The word‐recall task of the Alzheimer Disease Assessment Scale–Japanese (i.e. learning and recall of 10 words) was administered. The numbers of words recalled in each trial and those never recalled throughout the trials were compared for the two CDR groups. The serial‐position function was depicted for three parts (i.e. primary, middle, and recency). The CDR 0.5 group recalled significantly fewer words than the CDR 0 group. The number of never‐recalled words was greater in the CDR 0.5 group. A remarkable difference was found in the middle part of the word list. The number of never‐recalled words of the CDR 0.5 group was greater in the middle part. The large number of never‐recalled words accounted for the poor learning performance of very mild AD participants. The results suggested that very mild AD participants have difficulty in learning and retaining words in the middle part of the word‐list because of a functional decline of the central executive system.

Impaired Shifting of Visuospatial Attention in Alzheimer’s disease as Shown by the Covert Orienting Paradigm: Implications for Visual Construction Disability

Objective: To investigate impaired shifting of visuospatial attention in Alzheimer’s disease (AD) compared with age-matched controls. Method: An attention shifting was examined in 20 AD patients and 10 age-matched normal subjects by choice reaction time (CRT) and covert orienting paradigm. Visuospatial functions tests were also performed. For covert orienting, a peripheral spatial cue method was used, with stimulus-onset (SOA) between the cue and the target time varying from 250 to 2100 ms. Results: The CRT showed no difference between the AD and normal groups. However, the RTs costs plus benefits were greater in the AD than normal group for two SOA conditions independent of dementia severity. Individual profiles in the time course of cue validity revealed two AD subgroups, i.e., a normal pattern for the cue validity of time course, and an abnormal, ‘extinction-like’ pattern. The latter had a particular difficulty in performing visual construction and spatial attention. Conclusions: Focusing attention was relatively intact in AD. However, shifting of visuospatial attention was impaired in AD compared with normal controls. There was a subgroup whose deficits were not only in ‘disengagement,’ but their voluntary shifting of attention was affected. These subgroups may show clinically severe visuospatial symptoms in more advanced stage.