Prevalence and cognitive performances of vascular cognitive impairment no dementia in Japan: the Osaki–Tajiri Project

Abstract  Prevalence, magnetic resonance imaging (MRI) findings, cognitive function and depression are four major aspects of vascular cognitive impairment no dementia (vascular CIND). We performed a community-based study to examine these using 497 community-residents aged 65 years or older. Vascular CIND was defined as a clinical dementia rating (CDR) 0.5 with cerebrovascular disease. Several neuropsychological tests were performed, including MMSE, Geriatric Depression Scale (GDS), and Trail Making Test (TMT). Cerebrovascular disease and white matter lesions were visually assessed using MRI. Prevalence of vascular CIND, localization of cerebrovascular disease, and the relationships amongst MRI findings, white matter lesions, cognitive impairment and depression were analyzed. The prevalence of vascular CIND was 8.5% amongst the total population, corresponding to the rate being 37.2% amongst the CDR 0.5 participants. Compared with the CDR 0, the CDR 0.5 group had more subjects with strategic cerebrovascular disease in the thalamus, etc. No effects of cerebrovascular disease on MMSE and GDS scores were found, but the CDR 0.5/strategic cerebrovascular disease group showed impaired TMT-B scores. In the CDR 0 group, only anterior periventricular hyperintensity was associated with TMT-A score independent of cerebrovascular disease. A vascular CIND population was identified, and executive dysfunction in this population is probably based on an impaired fronto-subcortical circuit.     

Prevalence of dementia and dementing diseases in Japan: the Tajiri project

BACKGROUND: Vascular dementia (VaD) has been considered to be more prevalent than Alzheimer disease in Japan. However, this might be the result of overdiagnosis stemming from some problematic diagnosis of VaD or of the frequent use of magnetic resonance imaging to detect cerebrovascular disease in older adults. OBJECTIVES: We investigated the prevalence of dementia and the ratios of dementing diseases. The effects of different criteria for VaD (DSM-IV, Alzheimer's Disease Diagnostic and Treatment Centers [ADDTC], and National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS-AIREN]) were considered. Hippocampal atrophy and vascular contribution to dementia were evaluated using magnetic resonance imaging findings. METHODS: We targeted all residents 65 years and older (n = 3207) in Tajiri, Japan, and examined 1654 (participant group 1). Of these, 564 (participant group 2) were randomly selected, and 497 underwent magnetic resonance imaging and diagnosis of dementing diseases. RESULTS: We found the overall prevalence of dementia to be 8.5% (141/1654) in participant group 1. Of these, 21 (14.9%) had a history of stroke. Of the 113 participants who had a history of stroke independent of dementia, 18.6% (21/113) were demented. For participant group 2 (n = 497), 32 were demented. The ratio among the dementia for probable VaD based on the NINDS-AIREN criteria was 18.8% (6/32), whereas that for ischemic vascular dementia was 31.3% (10/32) according to the ADDTC criteria. CONCLUSION: We confirmed the overall prevalence of dementia in adults 65 years and older to be 8.5%. We found that VaD was not a common disorder according to the NINDS-AIREN criteria. Rather, the condition of possible Alzheimer disease with cerebrovascular disease was more common.     

Cerebral metabolic correlates of the clinical dementia rating scale in mild cognitive impairment

Mild cognitive impairment (MCI) is often a prodromal state of Alzheimer's disease (AD). Imaging studies have shown that metabolic deficits in cerebral regions known to be affected early by AD pathology are predictive of progression to AD. In the present article, the authors examine associations between clinical impairment (Clinical Dementia Rating scale sum of boxes [CDR-SB]) and regional deficits in glucose utilization in a sample of 41 patients with MCI, who underwent cerebral 18F-FDG PET for the measurement of regional glucose metabolism. A linear regression analysis with CDR-SB score as the independent variable and glucose metabolism as the dependent variable, adjusted for age, gender, and years of school education, was conducted in voxel-by-voxel fashion in SPM2. The regression analysis revealed a significant negative association between CDR-SB score and glucose metabolism in the right posterior cingulate gyrus (P < .001, uncorrected for multiple comparisons), which was independent from demographical variables. The authors conclude that clinical severity of impairments is already correlated with deficits in glucose metabolism in the stage of MCI.     

Progression to dementia in clinical subtypes of mild cognitive impairment

OBJECTIVE: To examine the outcome among patients diagnosed with different types of mild cognitive impairment (MCI). PATIENTS: A follow-up examination (average follow-up period: 3.49 +/- 2.2 years) was performed in 81 cognitively impaired, non-demented patients aged >55 years at baseline. RESULTS: 8 of 32 patients with amnestic MCI (25%), 22 of 41 patients with multiple-domain MCI (54%), and 3 of 8 patients with single non-memory MCI (37.5%) progressed to dementia. The clinical type of MCI is significantly associated with the likelihood of conversion to dementia. DISCUSSION: When the clinical syndrome of MCI evolves on a neurodegenerative basis, the multiple-domain type of MCI has a less favorable prognosis than the amnestic type and may represent a more advanced prodromal stage of dementia.     

The clinical dementia rating sum of box score in mild dementia

BACKGROUND: Making an early diagnosis of dementia is becoming increasingly important, but is difficult in practice. The Clinical Dementia Rating (CDR) scale is a widely used dementia staging instrument, yielding a global score and a summated score (sum of box score). This study examines the utility of the CDR sum of box score, rather than the CDR global score, in making a diagnosis of early dementia. OBJECTIVE: To determine whether the CDR sum of box score is predictive of an ICD-10 diagnosis of dementia in cases with mild cognitive deficits. METHODS: Clinical data recorded on our Memory Clinic database were examined for all patients seen over a 6-year period. Data were extracted from 276 first visits in which patients had scored 0.5 using the CDR global score. We examined the relationship between CDR sum of box score and consensus diagnosis of dementia using logistic regression. RESULTS: We found that increased CDR sum of box score was significantly associated with a higher probability of being assigned an ICD-10 diagnosis of dementia (p < 0.001). The odds ratio for the coefficient of CDR sum of box was 2.3 (95% CI 1.7-3.1), indicating that the likelihood of being diagnosed as having dementia increased by a factor of 2.3 for every point increase on the CDR sum of box score. CONCLUSION: These findings indicate that the CDR sum of box score provides additional information to the CDR global score in mild cases. The CDR sum of box score is a helpful indicator in making/excluding a diagnosis of dementia in people with mild cognitive deficits.     

Community based measures for managing mild cognitive impairment: The Osaki–Tajiri Project

A cross‐sectional study of aged patients with mild cognitive impairment in a local community was undertaken to investigate the clinical features of the condition, in addition to a longitudinal study to research its progression to cognitive deficit. Impairment of the basic functions of attention and executive function was confirmed, as opposed to impairment in the cognitive domain itself. Magnetic resonance imaging (MRI) findings showed a pattern close to that of healthy persons in their 80s, rather than that of patients with cognitive deficit. The results of the longitudinal study showed more progression to cognitive deficit when the clinical dementia rating was 0.5 in domains other than memory. No effects of lifestyle, internal diseases or psychosocial intervention were confirmed. In progression to Alzheimer's disease, generally low cognitive function and general atrophy were involved, whereas frontal lobe function, atrophy of the frontal and temporal lobes, white matter changes and cerebral infarction were related to progression to vascular dementia. Excessive dependence on primary prevention should be avoided for aged patients with mild cognitive impairment; rather, secondary prevention, using clinical dementia rating, psychological testing and MRI are desirable.     

Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia

BACKGROUND: The pathologic outcome of patients diagnosed with mild cognitive impairment (MCI) following progression to dementia is poorly understood. OBJECTIVE: To determine the pathologic substrates of dementia in cases with prior diagnosis of amnestic MCI. DESIGN AND SETTING: Community-based cohort. PATIENTS: Thirty-four subjects followed up prospectively as part of a community-based study who were diagnosed with amnestic MCI, progressed to clinical dementia, and underwent subsequent postmortem brain analysis. MAIN OUTCOME MEASURES: Neuropathologic analyses resulted in assignment of a primary pathologic diagnosis and included staging of Alzheimer pathologic abnormalities and identification of contributing vascular disease, Lewy bodies, and argyrophilic grains. RESULTS: Although the majority of subjects progressed both clinically and pathologically to Alzheimer disease (AD), 10 (29%) of them developed non-AD primary pathologic abnormalities. All of the cases were found to have sufficient pathologic abnormalities in mesial temporal lobe structures to account for their amnestic symptoms regardless of the cause. Most subjects were found to have secondary contributing pathologic abnormalities in addition to primary pathologic diagnoses. No significant differences between subjects with and without neuropathologically proven AD were detected in demographic variables, apolipoprotein E genotype, or cognitive test measures at onset of MCI, onset of dementia, or last clinical evaluation. CONCLUSIONS: The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.     

Impact of cognitive impairment on mild dementia patients and mild cognitive impairment patients and their informants

BACKGROUND: The aim of this study was to identify key aspects of the impact of cognitive impairment on patients with mild cognitive impairment (MCI) and mild probable Alzheimer disease (AD) and their informants, and identify overlap and differences between the groups. METHODS: Structured focus group discussions were conducted with MCI patients, AD patients, MCI informants, and AD informants. Participants were recruited from memory clinics in the U.K. and the U.S.A. A total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated. Sessions were content reviewed to identify key impacts of cognitive impairment; results were compared across diagnostic groups and for patients and informants. RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change in social and family roles, embarrassment and shame, emotionality, insight, and burden. Patients were able to discuss the impact of cognitive impairment on their lives and reported frustration with recognized memory problems, diminished self-confidence, fear of embarrassment, concerns about changing family roles due to cognitive impairment, and anxiety. Informants reported more symptoms and more impairment than did patients and indicated increased dependence on others among patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives and the lives of those close to them.     

Neuropsychosocial features of very mild Alzheimer's disease (CDR 0.5) and progression to dementia in a community: the Tajiri project

The borderline condition between normal aging and dementia should be detected to predict further deterioration. The authors cross-sectionally analyzed neuropsychological data, memory complaints, and social activities for community-dwelling older adults. The rate of decline from Clinical Dementia Rating (CDR) 0.5 to dementia during a 3-year interval was also analyzed. Short-term memory rather than long-term memory was found to be sensitive in distinguishing those with CDR 0 from those with CDR 0.5. Relatives' observations of memory decline rather than subjective memory complaints were significantly different. Participants with CDR 0.5 reported fewer problems with social activities than did their relatives. Ten of the 29 CDR 0.5 participants (34.5%) showed cognitive decline, the decliners showing lower scores on short-term memory and orientation at the baseline condition. The neuropsychological data showed CDR 0.5 to be similar to very mild Alzheimer's disease. It would be better if subjective complaints were excluded from the criteria of the borderline condition.     

Social behavior in mild cognitive impairment and early dementia

Social behavioral abnormalities are commonly seen in the later stages of dementia. However, there has been only limited empirical study of social functioning in the earlier stages of the disease, or in individuals diagnosed with mild cognitive impairment (MCI). The aim of the present study was to test whether these clinical groups show more socially inappropriate and prejudicial behavior relative to controls, as rated by informants. No group differences were identified for ratings of either socially appropriate behavior or stereotyping and prejudice. However, the results also indicated that informants rated participants with dementia as showing the most inappropriate behavior, and that these ratings were related to participants' degree of immediate logical memory impairment, but not to delayed memory recall or to more general neurocognitive decline as indexed by the Mini Mental State Examination. Together, these results have implications for an understanding of some of the changes in social function seen in abnormal adult aging.     

轻度认知障碍与无痴呆型血管性认知障碍患者的神经心理学特征

阿尔茨海默病（AD）和血管性痴呆（vascular dementia，VD）是临床常见的老年期痴呆类型。虽然长期以来受到广泛关注．但对其治疗收效甚微．近年逐渐将研究重点转向对其早期阶段的干预治疗。在这一临床需要下，针对阿尔茨海默病和血管性痴呆分别提出了轻度认知障碍（mild cognitive impairment，MCI）和血管性认知障碍（vascular cognitive impairment，VCI）的概念，力求对患者进行早期识别和干预，以延缓甚至阻止痴呆的发生、发展。     

Impaired instrumental activities of daily living affect conversion from mild cognitive impairment to dementia: the Osaki‐Tajiri Project

Aim: To determine whether impaired instrumental activities of daily living affect conversion from mild cognitive impairment to dementia for subjects in a community. Methods: This is a 7‐year retrospective study that followed 226 randomly selected participants from the Prevalence Study 1998 in Tajiri in northern Japan who had Clinical Dementia Rating 0.5. Instrumental activities of daily living levels were assessed with a 21‐item questionnaire. We analyzed the scores at baseline between the converters to dementia and non‐converters. Results: The converters had lower baseline scores on the ‘bed making’ and ‘mode of transportation’ items compared with the non‐converters; the former item was significant after a stepwise logistic regression analysis that excluded age and Mini‐Mental State Examination effects. In gender analysis, female converters had lower baseline scores on the ‘bed making’ and ‘cleaning’ items. For male participants, no items were found to have such an effect. Conclusions: We suggest that when individuals with mild cognitive impairment are limited in their performance of instrumental activities of daily living, this is predictive of dementia onset.     

Metabolic syndrome, mild cognitive impairment, and dementia

At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the reduced risk of predementia syndromes (ARCD and MCI), overall dementia, and VaD, but contrasting findings also exist on the possible role of MetS in AD. In the next future, trials could then be undertaken to determine if modifications of these risks including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. If MetS is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals at risk might offer new avenues for disease course modification. Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes.     

Agitation-associated behavioral symptoms in mild cognitive impairment and Alzheimer's dementia

Objectives: The aim of this study is to determine the prevalence of agitation in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia (AD), and to characterize the associated behavioral symptoms.

Method: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms was performed, including 268 MCI and 393 AD patients. Behavioral assessment was performed through Middelheim Frontality Score (MFS), Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia (CSDD). Agitated behavior was considered to be clinically relevant when one or more items of the Cohen-Mansfield Agitation Inventory (CMAI) occurred at least once a week.

Results: The prevalence of agitation in AD (76%) was higher than in MCI (60%; p < 0.001). Patients with agitation showed more severe frontal lobe, behavioral and depressive symptoms (MFS, Behave-AD and CSDD total scores). In agitated AD patients, all behavioral symptoms and types of agitation were more severe compared to non-agitated AD patients, but in agitated MCI patients only for diurnal rhythm disturbances. This resulted in more severe Behave-AD global scores in patients with agitation as compared to patients without agitation. Comparing MCI and AD patients, MCI patients with agitation showed more severe behavioral and depressive symptoms than AD patients without agitation. The structure of agitation in AD consisted of more aggressive and physically non-aggressive behavior than in MCI.

Conclusion: Frontal lobe, behavioral and depressive symptoms are more severe in MCI and AD patients with clinically relevant agitation as compared to patients without agitation. However, this association is less pronounced in MCI.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.