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Patients receiving hemodialysis (HD) have a higher risk of cognitive impairment and dementia than the general population. The accumulation of uremic toxins in the brain causes uremic encephalopathy, however, limited data exists to elucidate the effect of protein-bound uremic toxins on cognitive function. Here we investigate the effect of indole-3 acetic acid (IAA) and hippuric acid (HA), two different protein-bound uremic toxins from amino acid derivatives, on cognitive function by Silico and in a clinical study. Prevalent HD patients were enrolled in two independent hospitals. Serum IAA and HA were measured using mass spectrometry. Cognitive performance was measured using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Cognitive Abilities Screening Instrument (CASI) by trained psychologists. Using silico data to predict the effect of blood-brain barrier penetration was performed. The silico data demonstrated that IAA and HA had positive blood-brain barrier penetration ability. Amongst the 230 HD patients, serum IAA was associated with poor MMSE score (β= -0.90, 95% CI -1.61 to -0.19) and poor CASI score (β= -3.29, 95% CI -5.69 to -0.88) in stepwise multiple linear regression analysis. In logistic regression model, Serum IAA was also associated with cognitive impairment based on MMSE definition (OR, 1.96, 95% CI 1.10, 3.5) and CASI definition (OR, 2.09, 95% CI 1.21, 3.61). There was no correlation between Serum HA levels and cognitive function status. In conclusion, IAA, not HA, was associated with cognitive impairment in HD patients. Further large scale and prospective studies are needed to confirm our findings.

Background A cohort of children prenatally exposed to the 1945 atomic bombings in Japan revealed harmful effects of ionizing radiation in a variety of measures of cognitive function, including mental retardation. Here we examined cognitive function in the non-affected, now elderly, cohort. Methods From 2011-2015, using the Cognitive Abilities Screening Instrument and a maternal uterine radiation dose estimated with the 2002 dosimetry system, we evaluated 303 prenatally exposed subjects and their non-exposed controls from the Adult Health Study of the Radiation Effects Research Foundation, excluding those who had shown marked cognitive effects earlier. About 11% of the subjects were exposed to more than 250 mGy. We examined a self-reported disease history and, using regression analysis, evaluated the relationship between cognitive function and radiation exposures, adjusting for demographic factors. Results None of the subjects reported a history of dementia. We also did not find a significant radiation effect on cognitive function overall or in any gestational-week group. Education was associated with a significant effect, but educational level was not associated with radiation dose. Conclusion We found no significant radiation effect on cognitive function among 65- to 70-year-old subjects who were prenatally exposed to the bombings and did not have marked childhood cognitive function deterioration. The limitations of this study include a small sample size and potential bias pertaining to non-participation in the Adult Health Study or refusal of Cognitive Abilities Screening Instrument evaluation. Further investigations using various endpoints in other populations prenatally exposed to radiation are warranted.

OBJECTIVE To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke. METHODS Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (

Objectives Cholinesterase inhibitors (ChEIs) are the most effective treatment for Alzheimer disease (AD), but the response to treatment varies. Vascular lesions are associated with the pathogenesis of AD, and cerebral microbleeds (CMBs) are an indicator of hemorrhagic vascular pathology, which can be detected through susceptibility-weighted magnetic resonance imaging (SWMRI). This study investigated the association between CMBs and ChEI treatment response in patients with AD. Patients and Methods We reviewed the medical records of 112 Taiwanese people with mild to moderate AD and at least 2 years of ChEI treatment between 2009 and 2016. Their baseline CMBs were quantified using the Microbleed Anatomical Rating Scale on SWMRI. Cognitive function of the patients was assessed using the Mini–Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student t test and multivariable logistic regression were used to analyze the association between cognitive decline and CMBs. Results The mean age of the study population was 76.0 ± 8.0 years. In total, 79 out of 112 patients were women. The presence of deep, but not lobar CMBs at baseline was associated with a significant cognitive decline according to the MMSE and CASI, particularly in long-term memory, attention, orientation, mental manipulation, and verbal fluency. Among deep CMBs, those in the basal ganglia and thalamus were significantly associated with cognitive decline. Conclusions Deep CMBs, particularly those in the basal ganglia and thalamus, but not lobar CMBs, are associated with poor response to ChEI treatment in people with AD. This can serve as a biomarker for predicting ChEI treatment response.

Background. Patients undergoing hemodialysis experience a greater risk of cognitive impairment than the general population, but limited data elucidates the biomarkers on this. We evaluated the association of bone turnover markers on cognitive function among 251 prevalent hemodialysis enrollees in a cross-sectional study. Methods. 251 hemodialysis patients (median age=57.8, 55% men) and 37 control subjects (mean age=61.2, 56% men) without a prior stroke or dementia diagnosis were enrolled. Serum concentrations of 8 bone markers were analyzed as the association of cognitive function (Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI)) using linear regression analysis. Results. A lower cognitive function was noted in hemodialysis patients compared to control subjects. The receptor activator of nuclear factor kappa-B ligand (RANKL) was the only bone marker found to be associated with cognitive function (MoCA and CASI tests) in hemodialysis patients without a prior stroke or dementia diagnosis. In stepwise multiple linear regression analysis, the association remained significant in MoCA (β=1.14, 95% CI 0.17 to 2.11) and CASI (β=3.06, 95% CI 0.24 to 5.88). Short-term memory (β=0.52, 95% CI 0.01 to 1.02), mental manipulation (β=0.51, 95% CI 0.05 to 0.96), and abstract thinking (β=0.57, 95% CI 0.06 to 1.09) were the significant subdomains in the CASI score related to RANKL. Conclusions. Serum RANKL levels were potentially associated with better cognitive function in hemodialysis patients. Further large-scale and prospective studies are needed to confirm our findings.

IMPORTANCE: Age-related hearing difficulties can include problems with signal audibility and central auditory processing. Studies have demonstrated associations between audibility and dementia risk. To our knowledge, limited data exist to determine whether audibility, central processing, or both drive these associations. OBJECTIVE: To determine the associations between signal sensitivity, central auditory processing, and dementia and Alzheimer dementia (AD) risk. DESIGN, SETTING, AND PARTICIPANTS: This follow-up observational study of a sample from the prospective Adult Changes in Thought study of dementia risk was conducted at Kaiser Permanente Washington, a western Washington health care delivery system, and included 280 volunteer participants without dementia who were evaluated from October 2003 to February 2006 with follow-up through September 2018. Analyses began in 2019 and continued through 2021. EXPOSURES: Hearing tests included pure tone signal audibility, a monaural word recognition test, and 2 dichotic tests: the Dichotic Sentence Identification (DSI) test and the Dichotic Digits test (DDT). MAIN OUTCOMES AND MEASURES: Cognition was assessed biennially with the Cognitive Abilities Screening Instrument (range, 1-100; higher scores are better), and scores of less than 86 prompted clinical and neuropsychological evaluations. All data were reviewed at multidisciplinary consensus conferences, and standardized criteria were used to define incident cases of dementia and probable or possible AD. Cox proportional hazard models were used to determine associations with hearing test performance. RESULTS: A total of 280 participants (177 women [63%]; mean [SD] age, 79.5 [5.2] years). As of September 2018, there were 2196 person-years of follow-up (mean, 7.8 years) and 89 incident cases of dementia (66 not previously analyzed), of which 84 (94.4%) were AD (63 not previously analyzed). Compared with people with DSI scores of more than 80, the dementia adjusted hazard ratio (aHR) for DSI scores of less than 50 was 4.18 (95% CI, 2.37-7.38; P

Background/Objectives Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to “normal” aging, in the trajectory of scores on a global cognitive function test—the Cognitive Abilities Screening Instrument (CASI). Design A prospective cohort study. Setting Community-dwelling members of a U.S. health maintenance organization. Participants Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315). Measurements Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory (IRT) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed. Results Increased cognitive decline relative to “normal” aging was evident in CASI IRT at least 10 years before clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE e4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change point was estimated at an average of 3.1 years (95% confidence interval 3.0-3.2) before clinical diagnosis, after which cognitive decline appeared to accelerate. The change point did not differ by sex, education level, or APOE e4 genotype. There were subtle differences in trajectory slopes by sex and APOE e4 genotype, but not by education. Conclusion Decline in average global cognitive function was evident at least 10 years before clinical diagnosis of dementia. The decline accelerated about 3 years before clinical diagnosis.

Objectives:The condition of caregivers is important to the quality of care received by people with Parkinson’s disease (PD), especially at the late disease stages. This study addresses the distress placed on caregivers by participants’ neuropsychiatric symptoms at different stages of PD in TaiwanMethods:This prospective study enrolled 108 people with PD. All participants were examined with the Unified Parkinson’s Disease Rating Scale (UPDRS), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Clinical Dementia Rating (CDR) scale. Caregiver distress was measured using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D). Statistical analysis was used to explore the PD-related factors that contribute to caregiver distress.Results:The mean follow-up interval in the 108 PD participants were 24.0 ± 10.2 months with no participant lost to follow-up due to death. NPI-distress (the sum of NPI caregiver distress scale across the 12 domains of the NPI) was positively correlated with NPI-sum (the total score across the 12 domains of the NPI) (r = 0.787, p < 0.001), CDR (r = 0.403, p < 0.001), UPRDS (r = 0.276, p = 0.004), and disease duration (r = 0.246, p = 0.002), but negatively correlated with CASI (r = −0.237, p = 0.043) and MMSE (r = −0.281, p < 0.001). Multiple linear regression analysis showed that only NPI-sum and disease duration were independently correlated with NPI-distress.Conclusion:The disease duration and NPI-sum are independent predictors of caregiver distress in Taiwanese populations with PD. Early detection and reduction of neuropsychiatric symptoms in people with PD can help decrease caregiver distress.

Patients with chronic kidney disease have a greater risk of cognitive impairment. Cerebral uremic solute accumulation causes uremic encephalopathy; however, the association of protein-bound uremic toxins on cognitive function remains unclear. The present study aimed to investigate the association of two protein-bound uremic toxins, namely indoxyl sulfate (IS) and p-cresyl sulfate (PCS), on cognitive function in patients receiving hemodialysis (HD) for at least 90 days. Circulating free form IS and PCS were quantified by liquid chromatography/mass spectrometry. Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) were used to evaluate cognitive function. In total, 260 HD patients were recruited with a mean age of 58.1 ± 11.3 years, of which, 53.8% were men, 40% had diabetes, and 75.4% had hypertension. The analysis revealed that both free IS and free PCS were negatively associated with the CASI score and MMSE. After controlling for confounders, circulating free IS levels persisted to be negatively associated with MMSE scores [β = −0.62, 95% confidence interval (CI): −1.16 to −0.08] and CASI scores (β = −1.97, 95% CI: −3.78 to −0.16), mainly in the CASI domains of long-term memory, mental manipulation, language ability, and spatial construction. However, there was no correlation between free PCS and total MMSE or total CASI scores after controlling for confounders. In conclusion, circulating free form IS, but not PCS is associated with lower cognitive function test scores in HD patients. Thus, a further study is needed to evaluate whether a decrease in free IS levels can slow down cognitive decline in HD patients.

Background Past research has focused on risk factors for developing dementia, with increasing recognition of "resilient" people who live to old age with intact cognitive function despite pathological features of Alzheimer's disease (AD). Objective To evaluate demographic factors, mid-life characteristics, and non-AD neuropathology findings that may be associated with cognitive resilience to AD pathology. Methods We analyzed data from 276 autopsy cases with intermediate or high levels of AD pathology from the Adult Changes in Thought study. We defined cognitive resilience as having Cognitive Abilities Screening Instrument scores ≥86 within two years of death and no clinical dementia diagnosis; non-resilient people had dementia diagnoses from AD or other causes before death. We compared mid-life characteristics, demographics, and additional neuropathology findings between resilient and non-resilient people. We used multivariable logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for being resilient compared to not being resilient adjusting for demographic and neuropathology factors. Results We classified 68 (25%) people as resilient and 208 (75%) as not resilient. A greater proportion of resilient people had a college degree (50%) compared with non-resilient (32%, p = 0.01). The odds of being resilient were significantly increased among people with a college education (OR = 2.01, 95% CI = 1.01-3.99) and significantly reduced among people with additional non-AD neuropathology findings such as hippocampal sclerosis (OR = 0.28, 95% CI = 0.09-0.89) and microinfarcts (OR = 0.34, 95% CI = 0.15-0.78). Conclusion Increased education and absence of non-AD pathology may be independently associated with cognitive resilience, highlighting the importance of evaluating co-morbid factors in future research on mechanisms of cognitive resilience.

Background: The Cognitive Abilities Screening Instrument (CASI) assesses global cognitive function in people with dementia with 9 domains (i.e., long-term memory, short-term memory, concentration, orientation, attention, abstraction and judgment, language abilities, visual construction, and category fluency). However, the ecological, convergent, and discriminant validities of the CASI have not yet been examined. Purpose: This study designed to investigate these 3 validities of the CASI in people with dementia. Methods: Fifty-eight participants underwent assessments with the CASI, 3 functional measures, and 3 cognitive measures. Pearson's r was used to estimate correlations among the CASI and 3 functional measures for examining ecological validity. We computed correlations (r) among the CASI and 3 functional measures for examining convergent validity. An independent t-test was applied to compare the levels of disability, and ceiling/floor effects were analyzed for examining discriminative validity. Results: The CASI total score and domains had moderate to high correlations with 3 functional measures (r = 0.42–0.80), except in 2 CASI domains (i.e., attention and language). The CASI total score and domains showed moderate to high correlations with 3 cognitive measures (r = 0.45–0.93). The t-test results revealed significant differences (P

Background/Aims: Language dysfunction is a crucial feature of brain disorders. This study investigated language dysfunction in patients with dementia with or without parkinsonism by using an informant-based simple questionnaire. Methods: Language dysfunction in normal controls (NCs), and patients with Parkinson disease (PD), Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), or Alzheimer disease (AD) were analyzed and compared. Results: A total of 1,662 individuals were studied: 285 NCs, 157 PD patients, 161 PDD patients, 248 DLB patients, and 811 AD patients. Patients with PD displayed higher frequency of language dysfunction in several language domains than NC. Patients with PDD and DLB showed higher frequency of language dysfunction in most of the language domains than those with AD. A composite score of our simple questionnaire was comparable with the score for the language domain of the Cognitive Abilities Screening Instrument (CASI) in different stages of dementia due to Lewy body diseases or not. Conclusion: Our study showed that the informant-based simple questionnaire is a practical screening tool and is comparable with the language subscale of CASI. This tool can be applied in clinical practice and in the registration platform for rapid language dysfunction screening.

Resolving conflicts is an important cognitive ability of executive function, and it may decrease with cognitive decline. The flanker task is a practical test used to assess the ability to suppress responses that are inappropriate in a particular context. The aims of the present study were to investigate conflict monitoring of cognitive control in subjects with different levels of cognitive impairment, and clarify the usefulness of the flanker task in screening cognitive decline. We recruited 50 subjects with mild cognitive impairment (MCI) and 34 patients with Alzheimer's disease (AD), and 44 mentally healthy elderly subjects as a control group. To evaluate cognitive performance, each participant underwent a neuropsychological assessment using the Cognitive Abilities Screening Instrument and a modified flanker task. Compared with the normal controls and those with MCI, the patients with AD had a significantly lower accuracy rate and longer reaction time in both congruent and incongruent trials. The diagnosis of AD predicted significantly poorer performances on the flanker tasks. Furthermore, behavioral data of the patients with AD were significantly correlated with the results of neuropsychological tests. Our results indicated that executive cognitive deficits in conflict monitoring as detected by the flanker task were significantly impaired in the patients with AD. The flanker task could be a quick and easier alternative tool for screening AD among elderly people with suspicious cognitive impairment.

Background:The Cognitive Abilities Screening Instrument – Short (CASI-S) is a brief cognitive screening test. However, there is limited information regarding its applicability in primary care.Objectives:To ascertain whether the CASI-S differentiates between dementia patients and normal controls in primary care; to examine its correlation with other cognitive instruments, to analyze its internal consistency, test-retest stability, and diagnostic accuracy.Methods:In a case-control study, carried out at two Primary Care Units (PCUs) in the eastern region of the city of São Paulo, 47 older adults were diagnosed with dementia according to DSM-IV criteria (mean age = 76.81 ± 7.03 years), and 55 were classified as normal controls (mean age = 72.78 ± 7.37 years), by a multidisciplinary panel which had access to results from a comprehensive cognitive battery and the patients’ health data. The present analyses included results from the Mini-Mental State Examination (MMSE). The CASI-S was not used to determine diagnostic status.Results:The CASI-S was easily applied in the primary care setting. There was a significant performance difference (p < 0.001) between dementia patients (15.57 ± 7.40) and normal controls (26.67 ± 3.52) on the CASI-S. CASI-S scores correlated with age (ρ = −0.410, p < 0.001), educational level (ρ = 0.373, p < 0.001), and MMSE score (ρ = 0.793, p < 0.001). The internal consistency of the CASI-S was high (α = 0.848) and the correlation between test and retest was 0.688, suggesting adequate temporal stability. In the ROC curve analyses, scores of 22/23 generated an area under the curve of 0.907, with sensitivity of 93% and specificity of 81%.Conclusions:The CASI-S can be useful for dementia screening in primary care in Brazil.

There are conflicting findings regarding the link between sleep apnea and cognitive dysfunction.Investigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein ε-4 (APOE-ε4) allele.A diverse population (N = 1,752) underwent type 2 in-home polysomnography, which included measurement of percentage sleep time less than 90% oxyhemoglobin saturation (%Sat 90%) and apnea-hypopnea index (AHI). Epworth Sleepiness Scale score (ESS) and sleep apnea syndrome (SAS; AHI ≥ 5 and ESS 10) were also analyzed. Cognitive outcomes included the Cognitive Abilities Screening Instrument; Digit Symbol Coding (DSC) test; and Digit Span Tests (DST) Forward and Backward.Participants were 45.4% men, aged 68.1 years (SD, 9.1 yr) with a median AHI of 9.0 and mean ESS of 6.0. Approximately 9.7% had SAS, and 26.8% had at least one copy of the APOE-ε4 allele. In adjusted analyses, a 1-SD increase in %Sat 90% and ESS score were associated with a poorer attention and memory assessed by the DST Forward score (β = -0.12 [SE, 0.06] and β = -0.13 [SE, 0.06], respectively; P ≤ 0.05). SAS and higher ESS scores were also associated with poorer attention and processing speed as measured by the DSC (β = -0.69 [SE, 0.35] and β = -1.42 [SE, 0.35], respectively; P 0.05). The presence of APOE-ε4 allele modified the associations of %Sat 90% with DST forward and of ESS with DSC (POvernight hypoxemia and sleepiness were associated with cognition. The average effect estimates were small, similar to effect estimates for several other individual dementia risk factors. Associations were strongest in APOE-ε4 risk allele carriers. Our results (1) suggest that SDB be considered among a group of modifiable dementia risk factors, and (2) highlight the potential vulnerability of APOE-ε4 risk allele carriers with SDB.

Background The exergaming training involves motor as well as cognitive stimulation. Although exergame studies have been reported to have benefits in motor function, the effects of exergames on improving cognitive function remain inconclusive. Moreover, no study has been reported in stroke patients. Aim The objective of this study was to compare the cognitive effects of 2 weight-shifting controlled exergaming systems and conventional weight- shifting training in patients with chronic stroke. Design This was a single-blind randomized controlled trial. Setting All participants were recruited from a rehabilitation department of a tertiary hospital. Population Patients (N.=37) with chronic hemiplegic stroke. Methods Patients were randomly allocated to one of the Wii Fit, Tetrax biofeedback, or conventional weight-shifting training groups. All interventions were administered 30 minutes per session, twice a week for 12 weeks. We used total score and the 9 domain scores of Cognitive Abilities Screening Instrument Chinese version (CASI C-2.0), and Berg Balance Scale (BBS) as the outcome measures. The outcome measures were assessed before and after training, and at 3 months follow-up. Results There were no significant differences among the 3 groups in the percentage of change in CASI total score and BBS, either post intervention or at the 3-month follow-up. At assessing the percentage of change in each domain of CASI, we found significant differences among the 3 groups in the abstraction/judgment domain after intervention (Wii Fit 16.25 [9.77, 37.50]% vs. Tetrax 0.00 [-10.00, 0.00]% vs. weight-shift 11.00 [0.00, 14.38]%, P=0.01], and at the 3-month follow-up (Wii Fit 20.00 [10.83, 31.25]% vs. Tetrax -10.00 [-11.11, 10.00]% vs. weight-shifting 0.00 [-2.27, 11.46]%, P=0.01). The differences came from the differences between Wii Fit and Tetrax mainly. There were significant differences among the 3 groups in language domain after intervention (Wii Fit 0.00 [0.00, 5.54]% vs. Tetrax 0.00 [-3.00, 0.00]% vs. weight-shift 0.00 [0.00, 0.00]%, P=0.045), but not at the 3-month follow-up (P=0.13). There was no correlation between the percentage of change in BBS and CASI total score postintervention ( r=-0.15 P=0.38). Conclusions Wii Fit games training might be beneficial in some cognitive functions, such as abstraction/judgment, language in patients with chronic stroke. Wii Fit games, the commercial entertainment exergames, had superior effect in abstract/judgment and language domains as compared to the rehabilitation exergame (Tetrax balance system). Hence, Wii Fit games might be considered as a tool in post-stroke cognitive rehabilitation programs.

Background: Naming difficulties have recently garnered more interest in elderly individuals with mild cognitive impairment (MCI). We anticipate that naming tests with the consideration of response time can provide more informative and distinct neuropsychological profiles of individuals with MCI. Methods: Naming tests were administered to 76 elderly individuals with MCI and 149 healthy elderly (HE). We analyzed the impact of MCI on naming performance and occurrence of “delayed” response. We also validated the predictive power of naming tests with a time-constrained scoring system. Results: MCI participants performed poorer on the noun naming test than HE participants (p = 0.014). MCI was significantly associated with the occurrence of “delayed” response on the noun (odds ratio [OR] = 3.57; 95% confidence interval [CI] = 1.78-7.17) and verb naming tests (OR = 4.66; 95% CI = 2.07-10.46). The time-constrained naming scores were significantly better able to distinguish the MCI from the HE group than the conventional spontaneous naming score on both the noun (p < 0.001) and verb (p = 0.002) naming tests. Conclusions: Our findings broaden the knowledge related to the naming ability in individuals with MCI, with respect to the response time. We also confirmed the validity of the naming tests by applying the “delayed” responses as supplementary assessments in the diagnosis of MCI.

With the rapid growth of the global aging population, especially the oldest old, cognitive impairment has become a pervasive public health issue. In the United States, population-based studies suggest that age-related cognitive impairment affects 17%–34% of community-dwelling older adults (1). The demographic shift will likely increase the prevalence of age-related cognitive impairment, place considerable demands on the U.S. health care system, and impose physical, psychological, and financial stress on patients, their caregivers, and family members (2). U.S. Chinese aging population is one of the fastest growing subpopulations of older adults in the country. The life expectancy of U.S. Chinese older adults is in the mid 80s (3). Given the prevalence of cognitive impairment increasing with age, we can expect a growing demand for geriatric care in Chinese Americans. However, the prevalence of cognitive impairment is relatively underresearched among U.S. Chinese older adults due to the lack of large scale population-based studies examining the prevalence of cognitive impairment and related clinical diagnosis including dementia or Alzheimer’s disease. Despite the data gap, research suggests that there is evidence to believe that Asian Americans should have the same rates or even higher than that of Caucasian older adults (4,5). In addition, some methodological challenges may have dampened our systematic assessment of cognitive function among Chinese older adults and to make sensible comparisons with other racial/ethnic populations. First, there was a lack of population-based studies which administered a cognitive battery of tests to measure cognitive function and change in different cognitive abilities among Chinese older adults. Cognitive impairment of older adults is not limited to memory, but reflects a host of different definitions, including impairments in language, visual, or spatial awareness, and attention. Multiple measures of each ability may be valuable in reporting different cognitive abilities. Second, since individual differences found at baseline are likely to become more pronounced over time, forming composite cognitive measures allows researchers to combine tests of various difficulty levels to reflect a wider range of cognitive performance (6,7). The use of standard score, or z score, has the statistical advantage of increasing power by reducing random variability present within different tests that accommodate a wide range of cognitive function performance, and has been widely reported in population-based epidemiological studies of U.S. older adults (6,8). Whereas recent studies have further identified the use of composite scores to better demonstrate performance characteristics in studies of cognitive impairment compared with other scoring methods (9), such reports remain scare among Chinese American older adults. Third, the paucity of data on cognitive impairment can largely be attributed to the absence of culturally and linguistically sensitive instruments to screen and diagnose cognitive impairment among this population (10). There existed a number of measure developed and adapted for use in different cultures and for multiple languages, such as the Cognitive Abilities Screening Instrument (11) or the Cross-Cultural Neuropsychological Battery (12). Despite these tests have been piloted among groups of Chinese Americans, the sample size was small, and the majority of items were taken from a few screening scale which may be limited to measure a wide range of cognitive performances. Apart from existing methodological challenges, culturally specific perceptions, beliefs, and negative affects relating to cognitive impairment further present challenges to engaging Chinese American older adults to research studies (13), leaving Chinese older adults underrepresented in clinical studies, especially studies of cognitive impairment (14). As a result, we have incomplete knowledge on the scope of cognitive impairment and the effect of sociodemographic characteristics on the cognitive function among community-dwelling U.S. Chinese older adults, which is critical in informing culturally sensitive prevention strategies in the aging population. To fill in the knowledge void, in the current study, we adapted a battery of five tests for use with Chinese American older adults. These tests, including the Chinese Mini-Mental State Exam (C-MMSE), East Boston Memory Test (EBMT)-Immediate Recall, EBMT-Delayed Recall, Digit Span Backwards assessment, and Symbol Digit Modalities Test, have been validated and widely used among English-speaking and Spanish-speaking older adults in the United States (6,15). The objectives of this report is to: (i) describe cognitive function in an older U.S. Chinese populations using five cognitive function tests, (ii) explore the sociodemographic and self-reported health correlates of cognitive function, and (iii) describe the effect of key sociodemographic variables including age, sex, education on cognitive function.

BackgroundThe Cognitive Abilities Screening Instrument (CASI) is widely used to assess global cognitive function in patients with dementia. It contains nine cognitive domains, namely long-term memory, short-term memory, attention, mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency. However, test-retest reliability and minimal detectable change (MDC) of the CASI are largely unknown in patients with dementia, which limits its utility and the explanation of a score change.PurposeThe purpose of this study was to examine test-retest reliability and calculate MDC of the CASI in patients with dementia.MethodsFifty-two patients with dementia completed the CASI twice with a two-week interval. The frequencies of the scores in the Clinical Dementia Rating (0.5, 1, and ≥ 2) were 38.5, 36.5, and 25.0, respectively. Test-retest reliability was examined using intraclass correlation coefficient (ICC) for the total score and nine domains of the CASI. The MDC was calculated based on standard error of measurement.ResultsThe ICC value of the CASI total score was 0.97 while the ICC value for the nine domains were 0.65-0.92. The MDC values (MDC%) were 11.6 (12.9%), 2.8 (23.2%), 4.5 (41.2%), 3.4 (42.1%), 4.9 (49.2%), 5.3 (29.2%), 3.4 (28.8%), 2.2 (22.3%), 3.2 (32.1%), and 3.1 (30.7%) for CASI total score, long-term memory, short-term memory, attention, mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency, respectively.ConclusionOur results revealed that the CASI has sufficient test-retest reliability. The MDC values are useful in determining a real change (i.e., improvement or deterioration) between two assessments of an individual patient. However, four domains (i.e., short-term memory, attention, mental manipulation, and list-generating fluency) demonstrated lower ICC values and substantial random measurement errors. Clinicians and researchers should be cautious while using these four domains to explain score changes between repeated assessments of patients with dementia.

Vascular dementia (VaD) is a condition whereby decreased cerebral perfusion causes cognitive deterioration. We hypothesized that lesions of the anterior nucleus (AN) including the mammillo-thalamic tract cause a decline in the recollection of past episodes/events, and that the left thalamic infarction can cause frontal dysfunction through the “diaschisis.” We investigated 18 VaD cases with only left thalamic infarction. 99m Tc-ECD single photon emission computed tomography (SPECT) was used to assess regional cerebral blood flow (CBF). To test the first hypothesis, the scores on the Cognitive Abilities Screening Instrument (CASI) domain Recent memory or the rating on the Clinical Dementia Rating (CDR) domain Memory were analyzed. To test the second hypothesis, we selected the six regions of interest that correlated with the two measures, i.e., word fluency and/or depressive state, as assessed with the Geriatric Depression Scale (GDS). We found that all patients had amnesia, especially in the AN group, six of the eight patients had scores of 1+ on the CDR Memory scale, and all but one disclosed the CASI domain Recent memory impairment. There were significant correlations between the left anterior cingulate CBF and word fluency scores, and between the right rectal gyrus CBF and GDS scores. We suggest that these observations are due to a remote effect of the thalamic lesion.

Background As cognitive decline mostly occurs in late life, where typically it co-exists with many other ailments, it is important to consider frailty in understanding cognitive change. Objective Here, we examined the association of change in frailty status with cognitive trajectories in a well-studied cohort of older Japanese-American men. Methods Using the prospective Honolulu-Asia Aging Study (HAAS), 2,817 men of Japanese descent were followed (aged 71-93 at baseline). Starting in 1991 with follow-up health assessments every two to three years, cognition was measured using the Cognitive Abilities Screening Instrument (CASI). For this study, health data was used to construct an accumulation of deficits frailty index (FI). Using six waves of data, multilevel growth curve analyses were constructed to examine simultaneous changes in cognition in relation to changes in FI, controlling for baseline frailty, age, education, and APOE-ɛ4 status. Results On average, CASI scores declined by 2.0 points per year (95% confidence interval 1.9-2.1). Across six waves, each 10% within-person increase in frailty from baseline was associated with a 5.0 point reduction in CASI scores (95% confidence interval 4.7-5.2). Baseline frailty and age were associated both with lower initial CASI scores and with greater decline across the five follow-up assessments (p Discussion Cognition is adversely affected by impaired health status in old age. Using a multidimensional measure of frailty, both baseline status and within-person changes in frailty were predictive of cognitive trajectories.

Alzheimer's disease (AD) patients manifest not only memory impairment but also deficit of social judgment. However, contrary to frequently recognized deficit, only two neuropsychological tests have been established for assessing "judgment" : the Cognitive Abilities Screening Instrument domain Abstraction & judgment and the Picture Arrangement subscale of WAIS-III. For the former, we previously reported an association with decreased regional cerebral blood flow (rCBF) in the left parietal lobe. Herein, we analyzed the scores of the Picture Arrangement test. Forty-nine AD patients were classified into two groups, i.e., the high and low PA score groups. The 99m Tc-ECD SPECT investigation was performed with the voxel-based analysis using SPM5. The Mini-Mental State Examination subscores of "place orientation" showed a correlation with the PA scores. The low PA score group exhibited significantly decreased rCBFs in the Left Inferior Frontal Gyrus (LIFG), Left Superior Frontal Gyrus (LSFG) and Right Occipital Lobe (ROL), compared with the high PA score group. The ability of PA may be associated with the place orientation, which may be necessary to re-arrange the pictures. The ROL was related to visual recognition. The LSFG may be involved in executive function or "frontal reasoning."

Purpose To analyze cognitive changes in relation to mortality with the use of a multistate transition model. Methods In a prospective cohort study of Japanese Americans living in King County, WA, study (n = 1985) cognitive states were defined as the errors in the Cognitive Abilities Screening Instrument score. Transition probabilities were modeled by the use of a modified Poisson distribution with the Poisson mean and mortality dependent on the cognitive state and covariates. Results During an 8-year follow-up, 21.5% died (95% confidence interval [95% CI], 19.3–23.7), 26.6% experienced cognitive decline (95% CI, 24.2–29.1), and 51.9% remained stable or improved cognitively (95% CI, 49.2–54.6). In multivariable analyses, improvements were notably more likely to occur among younger, more-educated people and in women. Older age, male sex, and less education were each significantly related to mortality. Conclusions A multistate transition model can be used to estimate the impact of covariates on the individual probabilities of cognitive improvement, stability, decline, and death. This approach can have advantages for considering how interventions might work on patterns of cognitive change over time, especially if factors associated with the prevention of decline are also associated with risk of death.

Introduction Subjective chronic tinnitus is a common medical syndrome with a high frequency of cognitive impairment; however, the characteristics of cognitive impairment in chronic tinnitus are poorly understood. Investigating the scope of cognitive impairment across the severity spectrum of tinnitus patients may shed light on the issue. Methods A consecutive series of 207 subjective chronic tinnitus patients were classified into mild tinnitus group (n = 95) and severe tinnitus group (n = 112) by THI score (the cutoff THI scores were 37/38). These patients were assessed using the Cognitive Abilities Screening Instrument (CASI) and P300 event‐related potential. Results Although pure tone averages were not different between mild or severe tinnitus patients, severe tinnitus patients scored lower on the CASI assessment as well as almost all subdomains of CASI, particularly in items such as “short‐term memory,” “concentration or mental manipulation,” “orientation,” “abstraction and judgment,” “language abilities,” and “visual construction.” Furthermore, compared to mild tinnitus patients, severe tinnitus patients exhibited longer N2 and P3 latencies. Finally, a correlation analysis revealed that tinnitus severity was negatively correlated with CASI score and positively correlated with N2 and P3 latencies. Conclusions This study reveals that tinnitus patients on the severe end of the spectrum may be at risk for serious cognitive deficits, which may not be a secondary response to disease manifestations but a primary feature of the underlying disease.

Vitamin B12 is essential for the integrity of the central nervous system. However, performances in different cognitive domains relevant to vitamin B12 deficiency remain to be detailed. To date, there have been limited studies that examined the relationships between cognitions and structural neuroimaging in a single cohort of low-vitamin B12 status. The present study aimed to depict psychometrics and magnetic resonance imaging (MRI) morphometrics among patients with vitamin B12 deficiency, and to examine their inter-relations.We compared 34 consecutive patients with vitamin B12 deficiency (serum level ≤ 250 pg/ml) to 34 demographically matched controls by their cognitive performances and morphometric indices of brain MRI. The correlations between psychometrics and morphometrics were analyzed.The vitamin B12 deficiency group had lower scores than the controls on total scores of Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) (both P0.05), language (P0.01), orientation (P0.01), and mental manipulation (P0.05). The patients also showed a greater frontal horn ratio than the controls (P0.05). Bicaudate ratio, fronto-occipital ratio, uncotemporal index, and normalized interuncal distance all showed a strong correlation with the total score of MMSE and CASI (all P0.01). Among these psychometric and morphometric indices, pronounced correlations between bicaudate ratio and long-term memory, mental manipulation, orientation, language, and verbal fluency were noted (all P0.01).Vitamin B12 deficiency is associated with a global cognition decline with language, orientation, and mental manipulation selectively impaired. Preferential atrophy in frontal regions is the main neuroimaging feature. Although the frontal ratio highlights the relevant atrophy among patients, the bicaudate ratio might be the best index on the basis of its strong association with global cognition and related cognitive domains, implying dysfunction of fronto-subcortical circuits as the fundamental pathogenesis related to vitamin B12 deficiency.

The objective of this study was to investigate radiation effects on longitudinal pre-dementia cognitive decline among participants who developed dementia as well as on those who did not develop dementia during follow-up.Measuring cognitive function with the Cognitive Abilities Screening Instrument approximately every 2 years, we followed 1844 atomic bomb survivors participating in the Adult Health Study of the Radiation Effects Research Foundation from 1992 to 2011. Participants were adolescents or older when exposed to between 0 and 4 Gy. Approximately 15% and 40% of participants were exposed to ≥1 Gy and5 mGy, respectively. At study start, participants were dementia-free and between 60 and 80 years old. Three-quarters of the participants returned after baseline, averaging 8.4 years of follow-up. During follow-up, 313 developed dementia. We used cognitive scores before dementia onset for analysis and a mixed-effects model to estimate radiation effects on longitudinal change of cognition, adjusting for dementia occurrence, age, sex, and education.Cognition level was significantly associated with age, education, and dementia occurrence but not with radiation dose or sex. Cognitive decline accelerated with increasing age, especially among participants who developed dementia. Neither radiation nor education was significantly associated with the degree of deterioration with age. Radiation did not modify the different cognitive decline by dementia occurrence.Radiation did not significantly affect cognition among atomic bomb survivors exposed at or after adolescence.

Background: Recent data demonstrate that moderate consumption of alcohol (13–52 grams of ethanol per day) may be beneficial to cognitive functioning among older adults.Methods: Longitudinal growth curve analyses controlling for baseline age, body mass index (BMI), education/income, migrant status, smoking, history of diagnosed stroke, hypertension, coronary heart disease (CHD), depression, diabetes and stroke (time-varying) were used to examine the relationship between alcohol consumption, gender and cognitive performance over an 8-year follow-up period. The sample included 1624 Japanese American community-dwelling adults aged 65 and older who were cognitively intact at baseline and participated in at least one follow-up examination. Cognitive performance was measured using the Cognitive Abilities Screening Instrument (CASI; 0–100 point scale), a global test of cognitive function.Results: Current consumers (n=480) scored significantly (pn=1144; mean rate of change−3.77 CASI units). There was no significant main effect for gender, or an alcohol and gender interaction.Conclusions: This study provides further support regarding the beneficial effects of moderate alcohol consumption on cognitive performance over time. Observed benefits were not modified by gender. Future studies need to determine whether alcohol preserves cognition directly or whether other factors such as physiology or cultural drinking practices are driving the observed association.

Vascular dementia and vascular cognitive impairment have attracted more attention recently due to their association with increased risk of death and institutionalization. The purpose of the present study was to detect and identify the characteristics of cognitive impairments during the early stage of lacunar stroke. The subjects consisted of 23 consecutive first-ever acute lacunar infarction patients who were admitted to the Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, from November 2001 to October 2002. The National Institutes of Health Stroke Scale and Cognitive Abilities Screening Instrument (CASI) were used to evaluate stroke severity and cognitive function, and assessments were performed by a neurologist and psychologist, within 10 days of stroke onset. Of the 23 patients, 21 (91.3%) had CASI scores below their respective cutoff values and all patients had cognitive impairment in at least one cognitive domain in CASI. There were no significant correlations between CASI abnormality (below the cutoff value) and patient age, education, or the interval from stroke onset. Recent memory impairment was the most often impaired cognitive domain on CASI (19 patients, 82.6%). There were significant correlations between recent memory and “attention or concentration” (correlation coefficient, 0.52; p < 0.05), and “abstraction and judgment” (correlation coefficient, 0.44; p < 0.05). The correlations between recent memory and other domains were not significant. It was concluded that cognitive impairment after acute lacunar infarct is quite common and recent memory is the most often impaired cognitive domain. This may have been caused by the location of the specific lesion as well as by the impairment in “attention or concentration” or “abstraction and judgment”.

Background: Recent data demonstrate that moderate consumption of alcohol may be beneficial to cognition. Design: Longitudinal growth curve analyses controlling for variables related to cognition were used to examine the relationship between alcohol consumption, ethnic differences, gender, and cognition over a 4-year-follow-up period. Sample: The sample included 1,836 Japanese American and 2,581 Non-Hispanic White American community-dwelling adults age 65 and older who were cognitively intact at baseline and participated in at least one follow-up examination. Measurement: Cognitive performance was measured using the Cognitive Abilities Screening Instrument (CASI) and reaction time. Results: Current drinkers scored significantly higher on CASI over time than past drinkers or abstainers. The same association between alcohol and CASI was observed in both genders and both ethnic groups. Conclusion: This study provides support regarding the potential beneficial outcomes associated with alcohol consumption and cognition and that these benefits were not modified by gender or ethnicity.

The purpose of this study was to find means to increase the power of the Cognitive Abilities Screening Instrument, Chinese version (CASI C-2.0) in the screening of dementia. In assessing the performance of the CASI in dementia screening, it is a common practice to determine a cutoff score for the total CASI score and report the respective sensitivity and specificity. In this paper, we showed that an alternative scoring system, i.e., a weighted sum of the scores from the 9 domains in the CASI C-2.0, may improve its effectiveness in screening. In particular, short-term memory and orientation appeared to be the 2 most relevant domains and their combined score was shown to be more effective than the total score in screening dementia. We also showed that such a scoring system could be kept the same across examinees with different demographic backgrounds. With the weighted scoring system of the 9 domains for patients from the targeted population, we hope to make the CASI a clinically more powerful tool in screening dementia.

Although neuropsychological dysfunction is found among A-bomb survivors exposed in utero as it is among patients who receive central nervous system radiotherapy, neuropsychological examinations have not been conducted on the survivors. Its prevalence may be increased as a result of the increased rate of strokes reported among those exposed to a high radiation dose. In this study, we examined the effects of radiation exposure on cognitive function among adult survivors in the Adult Health Study (AHS). The study subjects were men and women born prior to September 1932 who had undergone biennial examinations during the period 1992-1996 in Hiroshima or 1993-1998 in Nagasaki. We evaluated cognitive performance for 3,113 subjects with the Cognitive Abilities Screening Instrument (CASI), and we examined the relationship between cognitive performance and potentially related factors (sex, age, city where the subjects were exposed, years of education, and radiation dose). In contrast to exposure to radiotherapy, exposure to atomic bomb radiation had no apparent effect on cognitive function. Factors that did affect cognitive function were age, sex, city and years of education. Further investigation, including examination of other neurological functions, is required before a final conclusion regarding radiation-induced neurological dysfunction can be reached.

The Cognitive Abilities Screening Instrument (CASI) contains nine cognitive domains. Its total score has been used to screen for dementia in epidemiological studies conducted in the US, Japan and Taiwan, but its usefulness in distinguishing different levels of dementia has not been examined. This study was conducted to compare CASI scores of patients with Alzheimer’s disease (AD) with different levels of severity of dementia. The CASI was administered to 475 AD patients with mild, moderate or severe dementia according to the Clinical Dementia Rating Scale. The patients’ scores were compared to the scores of 475 age-, education- and gender-matched control subjects. More specifically, each patient’s score, X, was transformed to a z score with reference to the mean and SD of the scores of the control group, where z = (X – mean)/SD. Then, the mean of the z scores and the percentage of patients with z scores of

Objectives The aims of the present study were to investigate the effect of hypertension and angiotensin-converting enzyme (ACE) genotypes on cognitive event-related potentials (ERPs), and whether the impact of ACE genotypes on P300 is related to the influence of hypertension. Methods Using the Cognitive Abilities Screening Instrument (CASI), we recruited 97 mentally healthy middle-aged and older adults. Medical histories were collected, and blood pressure, ACE insertion/deletion polymorphisms and ERPs in an auditory oddball task were measured for all participants. Results When the participants were stratified according to the presence or absence of hypertension, there were no differences in CASI score, percentage of ACE genotypes and ERPs. The subjects with the D/D homozygote displayed lower amplitude and longer latency of P300, although there were no differences in CASI score and the percentage of hypertension. Conclusions The subjects with the D/D genotype tended to have decreased amplitude and prolonged latency of P300 ERPs which reflected subtle cognitive impairment. There were no associations between hypertension, CASI score and P300 measurements. Significance Using ERPs, potential cognitive decline was linked to ACE genotypes, independently of the effect of hypertension.

Objective To describe the methodology utilized to evaluate cognitive function in the Multi-Ethnic Study of Atherosclerosis (MESA) and to present preliminary results by age, sex, and race/ethnicity. Design Cross-sectional measurements of a prospective observational cohort. Setting Residents of 6 U.S. communities free of cardiovascular disease at baseline (2000–02). Participants 4,591 adults who completed the fifth MESA clinical examination in 2011–12; mean age 70.3 (SD: 9.5) years, 53.1% women, 40.7% non-Hispanic white, 26.4% non-Hispanic black, 21.4% Hispanic, and 11.5% Chinese. Measurements The cognitive battery consisted of the Cognitive Abilities Screening Instrument (version 2) to evaluate global cognition, the Digit Symbol Code for processing speed and Digit Spans Forward and Backward to assess memory. Demographic, socioeconomic, and cultural covariates were also collected for descriptive statistics and multivariate modeling. Results Associations between socioeconomic factors and cognition revealed that age, race/ethnicity, education, occupational status, household income, health insurance type, household size, place of birth, years and generation in U.S., and the presence of the ApoE4 allele were significantly associated with performance on the cognitive tests, although patterns varied by specific test, racial/ethnicity, and sociocultural factors. Conclusion As many of the influencing cultural and socioeconomic factors measured here are complex, multifactorial, and may not be adequately quantified, caution has been recommended with regard to comparison and interpretation of racial/ethnic group performance differences from these cross-sectional models. These data provide a baseline for future exams and more comprehensive longitudinal analyses of the contributions of subclinical and clinical diseases to cognitive function and decline.

We constructed a Chinese version of the cognitive component of the Alzheimer’s Disease Assessment Scale (ADAS-Cog). In order to accommodate illiteracy, the Chinese version used pictures instead of words for assessing recall and recognition. The Chinese ADAS-Cog was administered to 125 individuals with no dementia, 127 with questionable dementia, and 77 with Alzheimer’s disease (AD). Their age range was 51–92 years and their education range was 0–20 years. The Chinese ADAS-Cog had high internal consistency (Cronbach’s alpha = 0.87) and very high interrater reliability (intraclass correlation coefficient, or ICC, = 0.99) and test-retest reliability (ICC = 0.96). It had high correlations with scores on the Clinical Dementia Rating Scale (Pearson’s r = 0.85), the Cognitive Abilities Screening Instrument (CASI, Pearson’s r = –0.88), and CASI-estimated scores on the Mini-Mental State Examination (Pearson’s r = –0.85). Performance on the Chinese ADAS-Cog was uninfluenced by age or gender, nor by education level except within the low education range of 0–6 years. Its memory items were best for early detection of dementia; its language items were best for monitoring the progression of dementia. This study found that the Chinese ADAS-Cog is a good instrument for use with Chinese AD patients.

OBJECTIVES: To examine the associations of subjective memory complaint (SMC) in old age with (a) objective test performance, (b) past and subsequent cognitive decline, and (c) depression. DESIGN: A group of community residents were examined twice during a 3-year period. SETTING: Two townships on a rural Chinese islet. PARTICIPANTS: A total of 543 men and women aged 65 years and older. MEASUREMENTS: During each examination, neurologists interviewed and examined all participants for dementia and asked the question, “Do you have trouble with your memory?” In addition, research assistants administered (a) the Cognitive Abilities Screening Instrument (CASI) to assess cognitive abilities, including long-term memory (LTM) and short-term memory (STM), and (b) the Geriatric Depression Scale-Short Version (GDS-S) to assess symptoms of depression. RESULTS: At each examination, almost half of the subjects acknowledged having trouble with their memory (the SMC+ group). At both examinations, the SMC+ group scored significantly lower on the CASI and significantly higher on the GDS-S than the SMC− group. However, the presence of SMC was not associated with faster cognitive decline over the past or subsequent 3 years. There were no consistent associations between SMC and the demographic variables of age, gender, and education at the two examinations. Logistic regression analysis showed that SMC was associated with poorer memory test scores after controlling for gender, age, education, and depression. CONCLUSIONS: SMC was associated with poorer objective memory performance even after controlling the effect of depression and demographic data, but SMC did not predict faster cognitive decline or dementia over 3 years. J Am Geriatr Soc 48: 295–299, 2000.

The Cognitive Abilities Screening Instrument (CASI) was developed by Japanese and American researchers, including the authors, to examine cognitive functions, based on previous neuropsychological tests, such as Hasegawa's Dementia Scale and the MMSE. From the Adult Health Study (AHS) population of the Radiation Effects Research Foundation, 2052 men and women aged 60 or over and living in Hiroshima were evaluated for their cognitive functions using the CASI. Dementia was diagnosed in 93 and 1,959 were considered not to suffer from dementia based on the DSM-III-R criteria using neurological examination and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) completed by caregivers. Multivariate regression analysis not only indicated that total score was higher with lower age and higher education but that the slope of its decrease is steeper with higher age and fewer years of education. The slope of score decrease with increase of age was steeper for women than for men. Furthermore, CASI items were categorized by domains of cognitive function. Multivariate regression analysis for each cognitive domain showed clear effects of age and level of education. The effect of age for the nondementia subjects was large in cognitive domains dealing with temporal orientation, short-term memory, and list-generating fluency. The most useful cognitive domains for diagnosing dementia were temporal orientation, short-term memory, and list-generating fluency, as was indicated by high sensitivity and specificity.

Background. Disproportionate increases in dementia morbidity in ethnic minorities challenge established screening methodologies because of language and culture barriers, varying access to health services, and a relative paucity of cross­ cultural data validating their use. Simple screening techniques adapted to a range of health and social service settings would ac­ celerate dementia detection and social and health services planning for demented minority elders. Methods. The effectiveness of the Clock Drawing Test (CDT) for dementia detection was compared with that of the Mini­ Mental State Examination (MMSE) and the Cognitive Abilities Screening Instrument (CASI) in community-dwelling elders of diverse linguistic, ethnic, and educational backgrounds. Subjects (N =295) were tested at home in their native languages (English, n =141; another language, n =154). An informant-based clinical dementia history and functional severity index de­ rived from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) protocols were used to classify subjects as probably demented (n =170), and probably not demented (n =125). Results. All tests were significantly affected by education ( p .05). Sensitivities and specificities for probable dementia were 82% and 92%, respectively, for the COT; 92% and 92% for the MMSE; and 93% and 97% for the CASI for subjects completing each test. However, in poorly educated non-English speakers, the COT detected demented subjects with higher sensitivity than the two longer instruments (sensitivity and specificity 85% and 94% for the COT, 46% and 100% for the MMSE, and 75% and 95% for the CASI). Moreover, less information was lost due to noncomple­ tion ofthe CDTthan the MMSE or CAS/ (severedementiaor CDT8%. MMSE/2%, and CAS/ 16%). Conclusions. Overall, the COT may be as effectiveas the MMSE or CASI as a first-level dementia screen for clinical use in multiethnic, multilingual samples of older adults. Its brevity (1-5 minutes), minimal language requirements, high acceptability, and lack of dependence on specialized testing materials are well adapted for screening of non-English-speaking elderly persons in settings where bilingual interpreters are not readily available and screening time is at a premium.

From April 1996 to January 1997, 74 Alzheimer disease (AD) patients and their caregivers were recruited for participation in a comprehensive assessment at the Veterans General Hospital-Taipei, a 2,198-bed tertiary care teaching hospital in Taipei, Taiwan. Diagnosis of AD was made according to criteria of the Diagnostic and Statistical Manual of Mental Disorders-III-R (DSM-III-R). All AD patients were tested with the Chinese version of Cognitive Abilities Screening Instrument (CASI). Their primary caregivers rated the patients using the Revised Memory and Behavior Problems Checklist (RMBPC), the short version of Geriatric Depression Scale (GDS-S), and obtained information about coping strategies using the Carer's Stress scale. The three subscale scores for memory-related problems, depression, and disruptive behavior were obtained from the RMBPC. Scores for three subscales for management of situations, meaning, and distress were obtained from the coping strategies' assessment. Depression was defined as a GDS-S score > or = 5. Among the 74 AD patients, 38 were men and 36 women. Their ages ranged from 47 to 90 years, with a mean age of 72.2 years (SD, 9.0). The CASI scores ranged from 1 to 88 (mean, 45.2; SD, 22.9). Thirty-three caregivers were men and 41 were women. Their age ranged from 20 to 85 years, with a mean age of 53.5 years (SD, 16.9). Twenty-six of the 74 caregivers (35.1%) were classified as depressed. The GDS-S scores of caregivers were correlated positively with the frequency of the use of a management of distress coping strategy and the frequency of the patients' disruptive behavior and were correlated negatively with the educational years of the caregivers.

The Revised Memory and Behavior Problems Checklist (RMBPC) is a 24-item caregiver report that measures observable behavioral and memory problems in dementia patients and their caregivers' reaction to these problems. The purpose of the present study was to evaluate the applicability of the RMBPC for use in Taiwanese patients with Alzheimer's disease (AD). The subjects included 76 AD patients (39 men and 37 women, mean age 72.3) and their caregivers (34 men and 42 women, mean age 53.5) who participated in a comprehensive assessment at the Veterans General Hospital-Taipei. The Chinese version of the Cognitive Abilities Screening Instrument was administered to the patients. Their caregivers rated the RMBPC and the short version of the Geriatric Depression Score (GDS). To assess the test-retest reliability, 30 caregivers rated a second RMBPC 3 days after the first evaluation. The mean score for the frequency rating on the RMBPC was 32.63 (SD = 12.44, range = 5–61) and the mean reaction score was 10.96 (SD = 11.53). The reaction score was significantly correlated with the GDS score (r = .363, p = .001). The Cronbach's alpha coefficients for frequency and reaction scores were .816 and .895 respectively. The test-retest reliabilities of total frequency and reaction scores were significantly correlated; overall correlations were .89 for frequency (p < .001) and .74 for reaction (p < .001). These findings suggest that the RMBPC be recommended as a reliable tool to assess behavioral and memory disturbance in Taiwanese AD patients.

Patients with vascular dementia (VaD) are often isolated, withdrawn from society because of negative symptoms and functional disabilities. The aim of this study was to detect factors associated with social withdrawal in patients with VaD. The participants were 36 institutionalized patients with VaD. Social withdrawal was assessed with the social withdrawal of the Multidimensional Observation Scale for Elderly Subjects (MOSES). Possible explanatory variables were the MOSES items depression and self-care, Cognitive Abilities Screening Instrument (CASI), apathy evaluation scale (AES), and Behavioral Pathology in Alzheimer’s Disease Frequency-Weighted Severity Scale (BEHAVE-ADFW). Multiple regression analyses were conducted for two groups: Analysis 1 was performed in all patients (N = 36) and Analysis 2 was performed in the patients with the ability to move by themselves (i.e., independent walking or independent movement with a cane or a wheelchair; n = 28). In Analysis 1, MOSES item social withdrawal was correlated with AES and MOSES item self-care. In Analysis 2, MOSES item social withdrawal was correlated with AES and CASI domain abstraction and judgment. Decreased social activities of VaD were not related to general cognitive function or depression. Disturbed activities of daily living (ADLs) for self-care may involve decreased frontal lobe function, indicating that comprehensive rehabilitation for both ADL and dementia are needed to improve the social activities of patients with VaD.

Many cognitively normal older adults have underlying neuropathologic changes of Alzheimer's disease (AD), vascular brain injury (VBI), or Lewy body disease (LBD), which confer an increased risk of dementia. The current study focused on the association between multiple neuropathologic indices and performance on specific cognitive domains in a community sample of older adults. Of 438 participants in the Adult Changes in Thought population-based study of brain aging who were autopsied, 363 subjects had cognitive testing at their final study visit and were included. Associations were measured between performance on the Cognitive Abilities Screening Instrument prior to death and neuropathologic endpoints, including AD neuropathologic changes, LBD, cerebral amyloid angiopathy, and measures of VBI. Braak stage for neurofibrillary tangles, lower brain weight, and VBI as measured by cerebral cortical microvascular lesions (μVBI) explained a significant proportion of the variance associated with global cognitive test performance (R2 = 0.31, p < 0.0001) both in the entire sample and when analysis was restricted to non-demented subjects (R2 = 0.23, p < 0.0001). Specific cognitive domains were differentially related to neuropathologic lesion type: memory and executive function with AD pathologic changes and cortical μVBI, executive function with subcortical μVBI, and visuospatial construction with LBD. Thus, neuropathologic lesions of LBD and μVBI are associated with poorer cognitive performance over and above AD neuropathologic changes in subjects without dementia in this cohort. These findings underscore that cognitive impairment is a complex convergent trait that has important implications for clinical investigation and medical management of older adults.

Objective To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. Design Prospective population based cohort. Setting Integrated healthcare delivery system, Seattle, Washington. Participants 3434 participants aged ≥65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. Main outcomes measures The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer’s disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. Results Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer’s disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥121 TSDDs. Results were similar for Alzheimer’s disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. Conclusion The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.

SynopsisA community survey of dementia was conducted on a Chinese islet. A total of 221 men and 234 women in the age range of 50–92 were assessed. The Cognitive Abilities Screening Instrument (CASI), a 100-point cognitive test designed for cross-cultural studies and adapted in Chinese for individuals with little or no formal education, was administered twice by trained field workers with a retest interval of 3 to 4 weeks. In addition, all participants were assessed by physicians who did not know the CASI scores. The physicians' assessment included a complete neurological examination, plus semi-structured tests and interviews covering cognitive abilities, daily activities, depression, cerebrovascular disease, and Parkinson's disease. Dementia was diagnosed by consensus among the physicians according to the DSM-III-R criteria. Among the 455 participants, 16 cases of dementia were identified, including 13 with probable Alzheimer's disease and 1 each with vascular dementia, Parkinson's disease, and alcoholism. The rates of dementia were 0, 3·9 and 11·5% for the age groups of 50–69, 70–79 and 80–92; and 4·4, 2·0 and 0% for the education groups of 0–1, 2–6 and 7–15 years of schooling. No sex difference was found after controlling for education. The Chinese version of the CASI had an intraclass retest reliability of 0·90. Using a cut-off score of ≤ 50 for dementia, the sensitivity was 0·88 and the specificity was 0·94. The preliminary study suggests that the CASI can be used in Chinese populations with generally low education levels and that Alzheimer's disease was the most common type of dementia in this population.

The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. Scores of the Mini-Mental State Examination, the Modified Mini-Mental State Test, and the Hasegawa Dementia Screening Scale can also be estimated from subsets of the CASI items. Pilot testing conducted in Japan and in the United States has demonstrated its cross-cultural applicability and its usefulness in screening for dementia, in monitoring disease progression, and in providing profiles of cognitive impairment. Typical administration time is 15 to 20 minutes. Record form, manual, videotape of test administration, and quizzes to qualify potential users on the administration and scoring of the CASI are available upon request.

Objective: The aim of this study was to compare two screening methods, total score of the Cognitive Abilities Screening Instrument (CASIT) and the combined score for the short-term memory and orientation domains (CASIR) for screening and grading probable Alzheimer's disease (AD), based on their correlations with voxel-based morphometry (VBM). Materials and methods: Forty-five subjects with probable AD and normal controls underwent magnetic resonance imaging and CASI testing. Their corresponding T1-weighted magnetic resonance images were analyzed using VBM. Results: VBM results showed that in moderate-to-severe AD subgroups, significant wholebrain gray matter loss was detected using both CASIT and CASIR. Significantly more voxels were detected using the CASIT compared with the CASIR system in mild AD subjects (Pb.05). Conclusions: Based on their correlations with VBM results, there is no significant difference for CASIR and CASIT for grading moderate-to-severe AD subgroups, and CASIR scoring system may be more accurate and effective than the CASIT for screening mild AD.

Objective: To identify clinical manifestations and neuropsychological effects of Alzheimer disease (AD) in apolipoprotein (ApoE) e4 carriers and to investigate the relationships between ApoE HhaI polymorphism and apolipoprotein C1 (APOC1) HpaI polymorphism in Taiwanese patients with AD. Participants and methods: A total of 127 patients with AD and 191 elderly individuals were screened for ApoE and APOC1 polymorphism. All patients underwent neuropsychological testing, including a Mini-Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and/or the Visual Association Memory Test (VAMT) with Cognitive Abilities Screening Instrument. Results: The frequencies of the e4 and A alleles were significantly higher in the AD group. In the patients with AD, the e4 and A allele effects on those with an age-of-onset of 60 to 79 years were stronger than those with an age-of-onset of 80 years or higher. Visual Association Memory Test performance was significantly worse in e4-allele carriers but not in A-allele carriers, in the early AD, particularly in those affected with AD for less than 2 years. Although there was no statistically significant difference in genotypic frequency between patients and controls, the 2 genes were linked. In addition, the presence of the AA genotype concomitant with the e4 allele may be better associated with AD diagnosis than either factor alone. Conclusion: We conclude that the e4 allele affects neuropsychological performance and illness morbidity. Concomitantly, ApoE e4 and APOC1 A alleles have a better association with AD than ApoE e4 alone. In addition, APOC1 may partially contribute to the pathogenesis of AD, but the nature of its relationship with e4 requires further investigation.

Given the need for tools for early and accurate diagnosis, prediction of disease progression, and monitoring efficacy of therapeutic agents for AD, the study of cerebrospinal fluid (CSF) biomarkers has become a rapidly growing field of research. Several studies have reported conflicting data regarding the relationships between CSF biomarkers and dementia severity. In this study, we have focused on the identification of CSF biomarkers and their correlations with the impairment of different cognitive domains measured using the Cognitive Abilities Screening Instrument (CASI). Patients with AD (n=28), non-AD dementia (n=16), other neurological disorders (OND, n=14), and healthy controls (HC, n=21) were enrolled. Our results revealed significantly higher CSF total tau (t-tau) and lower amyloid-beta(42) levels in AD patients compared with those in HC and OND groups. Moreover, our data show that CSF t-tau levels, but not Abeta(42) levels, have an inverse correlation with the score of short-term memory in CASI for patients with AD (Spearman: r=-0.444; p=0.018). This data might indicate that the higher CSF t-tau level is associated with more NFT pathology and more severe impairment of short-term memory in AD patients.

Background The neurologic background of confabulations with reference to delusions or cognitive functions has not been clarified in Alzheimer disease (AD). Methods Confabulations of 41 AD patients and 12 healthy controls were studied using the Modified Confabulation Battery. The mini-mental state examination and Cognitive Abilities Screening Instrument were used for cognitive evaluations. Cerebral atrophy was assessed by voxel-based–morphometry of magnetic resonance imaging and the correlations with confabulations were analyzed by statistical parametric mapping 2. For the relations with delusion, the AD patients were divided into the delusion and nondelusion groups. The single photon emission computed tomography was performed to evaluate cerebral blood flow and the group difference was analyzed by statistical nonparametric mapping 3. Results The AD patients exhibited more confabulations on episodic memory questions compared with semantic questions. The semantic confabulation scores correlated with mini-mental state examination and most Cognitive Abilities Screening Instrument domains scores, and correlated with atrophy in the anterior cingulate, bilateral medial temporal, and right middle temporal gyrus. The delusion group exhibited more episodic confabulations and had lower prefrontal blood flow than the nondelusion group. Conclusions Different mechanisms are involved in confabulations between semantic and episodic memories in AD. Episodic confabulation is affected by delusion related to frontal dysfunction, and semantic confabulation is associated with cognitive dysfunction.

Objective To cocalibrate the Mini-Mental State Examination, the Modified Mini-Mental State, the Cognitive Abilities Screening Instrument, and the Community Screening Instrument for Dementia using item response theory (IRT) to compare screening cut points used to identify cases of dementia from different studies, to compare measurement properties of the tests, and to explore the implications of these measurement properties on longitudinal studies of cognitive functioning over time. Study Design and Setting We used cross-sectional data from three large ( n > 1000) community-based studies of cognitive functioning in the elderly. We used IRT to cocalibrate the scales and performed simulations of longitudinal studies. Results Screening cut points varied quite widely across studies. The four tests have curvilinear scaling and varied levels of measurement precision, with more measurement error at higher levels of cognitive functioning. In longitudinal simulations, IRT scores always performed better than standard scoring, whereas a strategy to account for varying measurement precision had mixed results. Conclusion Cocalibration allows direct comparison of cognitive functioning in studies using any of these four tests. Standard scoring appears to be a poor choice for analysis of longitudinal cognitive testing data. More research is needed into the implications of varying levels of measurement precision.