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Introduction We modeled associations between glycated hemoglobin (HbA1c) levels (8%) and cognitive and physical function among adults 80+ years of age with diabetes and determined whether associations differ by frailty, multimorbidity, and disability. Methods A total of 316, adults with diabetes, 80+ years of age, were from the Adult Changes in Thought Study. The Cognitive Abilities Screening Instrument Item Response Theory (CASI‐IRT) measured cognition. Short performance‐based physical function (sPPF) and gait speed measured physical function. Glycosylated hemoglobin (HbA1c) levels were from clinical measurements. Analyses estimated associations between average HbA1c levels (8%) and functional outcomes using linear regressions estimated with generalized estimating equations. Results sPPF scores did not differ significantly by HbA1c levels. Gait speed did, but only for non‐frail individuals; those with HbA1c >8% were slower (‐0.10 m/s [95% CI, −0.16 to −0.04]) compared to those with HbA1c 7% to 8%. The association between HbA1c and CASI‐IRT varied with age (interaction P = 0.04). At age 80, for example, relative to people with HbA1c levels of 7% to 8%, CASI‐IRT scores were, on average, 0.18 points lower (95% CI, −0.35 to −0.02) for people with HbA1c 8%. At older ages, these estimated differences were attenuated. Estimated associations were not modified by multimorbidity or disability. Discussion Moderate HbA1c levels of 7% to 8% were associated with better cognition in early but not late octogenarians with diabetes. Furthermore, HbA1c >8% was associated with slower gait speed among those without frailty. These results add to an evidence base for determining glucose targets for very old adults with diabetes.

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.

Aim The response to donepezil in patients with Alzheimer's disease varies, and it is important to identify the potential responder before therapy. Cerebral white matter changes (WMC) are frequently observed in older patients, and the effect of WMC on therapeutic response remains controversial. The present study aimed to investigate the relationships between the location of WMC, severe WMC and the response to donepezil. Methods Among 418 patients with Alzheimer's disease receiving donepezil, 196 patients were eligible for analysis. Five brain areas on each side were analyzed using computed tomography scans and the Age-Related White Matter Changes Rating Scale before therapy. The Cognitive Abilities Screening Instrument was used annually. Patients were defined as responders if their baseline Cognitive Abilities Screening Instrument score minus their follow-up Cognitive Abilities Screening Instrument score was ≤0. Results There was no significant difference in demographic data between responder and non-responder groups. Patients in the responder group had significantly less involvement of WMC in the frontal area (P = 0.0213) and nearly a trend for less involvement of WMC in the basal ganglia (P = 0.1103). After adjustment for age, sex, education, polymorphism of apolipoprotein E, hypertension and diabetes, WMC in the frontal area (OR 0.446, P = 0.0139) and basal ganglia (OR 0.243, P = 0.0380) were significantly associated with a reduced therapeutic response. Conclusions Patients with WMC in the frontal area and basal ganglia had significant decreases in their therapeutic response to donepezil. The location of WMC, independent of their severity, might be associated with the therapeutic response in patient with Alzheimer's disease. Geriatr Gerontol Int 2018; 18: 123–129.

Aim The relationship between declining performance, as measured by changes in reaction time, and declining cognitive function has not been critically studied. The aim of the present study was to investigate the association between reaction time during a task and cognitive ability in elderly Taiwanese individuals. Methods Patients aged 65 years or older with mild cognitive impairment (MCI) (n = 33) and Alzheimer’s disease (n = 26) were recruited from the neurology clinic of a regional hospital in southern Taiwan. In addition, 28 healthy controls aged 65 years or older were recruited from the community. The cognitive performance of the study participants was assessed using the Cognitive Abilities Screening Instrument (CASI). A computer-administered simple reaction time (SRT) task and a flanker reaction time (FRT) task were administered to assess participants’ cognitive function. A non-parametric Kruskal–Wallis test was performed to compare CASI scores, SRT, and FRT among the three groups. anova was also used to compare CASI scores, inverse-transformed SRT, and inverse-transformed FRT among the three groups, with adjustment for age and years of education. Additionally, Pearson’s partial correlation coefficients were used to assess the association of CASI scores with inverse-transformed SRT, and inverse-transformed FRT within each of the three groups. Results Significant differences in CASI scores, SRT, and FRT were found between the Alzheimer’s disease group and the other two groups, either with or without adjustment for age or education. The reaction time of patients with Alzheimer’s disease was significantly slower than the other two groups. Moreover, significant correlation between CASI and FRT was found in patients with MCI. Conclusion Altered performance in a speed task was observed in patients with MCI. The FRT task should further be explored for its role as a marker for cognitive decline in elderly individuals, particularly in those with MCI.

Aim The aim of this study was to investigate the clinical utility of the Functional Independence Measure (FIM), and especially FIM-Cognition (FIM-C) scores, in patients with Alzheimer's disease (AD) and vascular dementia (VaD), and to determine the influence of behavioural and psychological symptoms of dementia (BPSD) on FIM-C scores. Methods This was a cross-sectional survey of 37 AD and 40 VaD patients. Cognitive function was assessed with the Cognitive Abilities Screening Instrument. Activities of daily living were evaluated with the FIM and the Barthel Index. BPSD were assessed with the Behavioural Pathology in Alzheimer's Disease Frequency Weighted Severity Scale. Results For both groups, Spearman's correlations were found between FIM-Motor and Barthel Index scores and between FIM-C and Mini Mental State Examination scores. Each FIM-C subscore was correlated with Cognitive Abilities Screening Instrument scores in both groups, except for the FIM-C Social interaction subscore in VaD. VaD patients showing Activity Disturbance and Aggressiveness on the Behavioural Pathology in Alzheimer's Disease Frequency Weighted Severity Scale had significantly lower FIM-C Memory and Social interaction subscores than those without BPSD. Conclusion The results suggest that the FIM-Motor and FIM-C scales are useful measures of physical and cognitive disabilities in patients with AD and VaD. The FIM-C profile of AD may reflect global cognitive function, while that of VaD may be more influenced by BPSD.

The integrated effect of the cholesterol and CYP46 genotypes on the risk of cognitive decline needs to be determined. Using the Cognitive Abilities Screening Instrument (CASI), 145 mentally healthy middle-aged and older adults were recruited to investigate the influence of cholesterol and CYP46 genotypes on cognitive event-related potentials (ERPs). The subjects with a high low-density lipoprotein cholesterol (LDL-C) level displayed significantly lower amplitude ERPs, although the CASI scores showed no difference. There was no association between the CYP46 genotypes, CASI scores, cholesterol levels, and measures of ERPs. No interaction between LDL-C level and CYP46 genotypes was noted. The LDL-C level is an independent predictor of low P300 amplitude. Prevention and treatment of high cholesterol may be of potential benefit in reducing cognitive impairment.

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.

Objectives: Cognitive impairment may interfere with psychosocial functioning in bipolar disorder (BD). There is limited information regarding the cognitive function of elderly bipolar patients with onset at a young age. The present study aimed to investigate the frequency and the determinants of cognitive impairment in elderly early-onset bipolar patients. Methods: Using the Clock-drawing Test (CDT), the Mini Mental State Examination (MMSE), and the Cognitive Abilities Screening Instrument (CASI), we examined euthymic patients with bipolar I disorder in Taiwan, aged 60 years and older. Clinical data were obtained by reviewing medical records and personal interviews with patients and their family members. The onset of BD prior to the age of 40 years is defined as ‘early-onset’. Results: Of the 52 early-onset patients, 42.3% were determined to have cognitive impairment by exhibiting either abnormal CDT or education-adjusted MMSE scores. In a multiple regression model, years of education and the age at the last manic/hypomanic (but not depressive) episode accounted for the greatest variance in both MMSE and CASI scores. While educational level and the age at the last manic/hypomanic episode were not considered in the regression model, onset with depressive syndrome and current age explained 21.5% of the variance in MMSE scores. Age at the first depressive episode, the first manic episode before the age of 40 years, and comorbid diabetes accounted for 16.7% of the variance in CASI scores. Conclusions: There appeared to be a sizable proportion of elderly early-onset bipolar patients having cognitive impairment. It is suggested that clinical manifestation of first-onset affective episode and impact of medical comorbidity affect the cognition of early-onset BD in later life.

Objective: To determine the type of cognitive deficits occurring 3 to 6 years before onset of dementia in a population sample. Design: A prospective study in which cognitive deficits in participants who had incident dementia at the 6-year follow-up were examined at baseline and 3 years. Setting: Honolulu, Hawaii. Participants: Three thousand seven hundred thirty-four Japanese-American men aged 71 to 93 at baseline. At the 6-year follow-up, there were 52 incident cases of dementia, and 1,559 controls. Measurements: The Cognitive Abilities Screening Instrument (CASI) and a questionnaire on subjective memory problems were administered at baseline. Dementia was assessed at baseline and at 3-year and 6-year follow-ups. Results: Subjects who had incident dementia at 6-year follow-up, had showed deficits 3 to 6 years earlier in the CASI domain of episodic memory and in the questionnaire covering subjective memory problems. Up to 3 years before onset, there was worsening of the episodic memory deficit from baseline and new deficits in language, verbal fluency, and orientation. Conclusion: Cognitive deficits and awareness of memory problems are frequently present several years before dementia onset. The predictive value of these deficits is not large enough to allow earlier diagnosis of dementia, but information about such deficits may be useful as criteria for mild cognitive impairment.

Lower hemoglobin (Hb) levels are a common feature in the elderly. The present study recruited 180 healthy elderly men. Participants were assessed using the Geriatric Depression Scale, the Cognitive Abilities Screening Instrument Chinese version, and the Wechsler Digit Span Task test. The mean age of the participants was 85.8 years (SD = 10.5). Pearson's correlation tests demonstrated that Hb concentrations negatively correlated with Geriatric Depression Scale (r = -0.245, P = 0.001), but did not correlate with Cognitive Abilities Screening Instrument, Forward or Backward Digit Span tests. Lower Hb levels, therefore, were associated with depression in the elderly men. Language: en

Background As elderly populations grow, dementia detection in the community is increasingly needed. Existing screens are largely unused because of time and training requirements. We developed the Mini-Cog, a brief dementia screen with high sensitivity, specificity, and acceptability. Here we describe the development of its scoring algorithm, its receiver operating characteristics (ROC), and the generalizability of its clock drawing scoring system. Sample and methods A total of 249 multi-lingual older adults were examined. Scores on the three-item recall task and the clock drawing task (CDT-CERAD version) were combined to create an optimal algorithm. Receiver operating characteristics for seven alternatives were compared with those of the MMSE and the CASI using expert raters. To assess the CDT scoring generalizability, 20 naive raters, without explicit instructions or prior CDT exposure, scored 80 randomly selected clocks as ‘normal’ or ‘abnormal’ (20 from each of four CERAD categories). Results An algorithm maximizing sensitivity and correct diagnosis was defined. Its ROC compared favorably with those of the MMSE and CASI. CDT concordance between naive and trained raters was >98% for normal, moderately and severely impaired clocks, but lower (60%) for mildly impaired clocks. Recalculation of the Mini-Cog's performance, assuming that naive raters would score all mildly impaired CDTs in the full sample as normal, retained high sensitivity (97%) and specificity (95%). Conclusion The Mini-Cog algorithm performs well with simple clock scoring techniques. The results suggest that the Mini-Cog may be used successfully by relatively untrained raters as a first-stage dementia screen. Further research is needed to characterize the Mini-Cog's utility when population dementia prevalences are low. Copyright © 2000 John Wiley & Sons, Ltd.

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.

OBJECTIVES: To examine the association of years spent in Japan during childhood with cognitive test performance in late life among Japanese American men, and to assess the influence of the language used for testing on this association. DESIGN: A cross-sectional study. SETTING/PARTICIPANTS: A total of 3734 Japanese American men, aged 71–93 years, who were first- or second-generation migrants and living on Oahu Island, Hawaii. MEASUREMENTS: The outcome variable was cognitive test performance assessed using the Cognitive Abilities Screening Instrument (CASI), which was developed for cross-cultural studies of cognitive impairment. The explanatory variable of main interest was the number of years spent in Japan during school-age childhood years (ages 6–17). The associations of CASI scores with childhood years in Japan was evaluated using a stepwise multiple linear regression model in which a total of 40 potential confounders were included as covariates. RESULTS: In the total sample, there was an inverse association between CASI scores and middle childhood years in Japan. This association remained significant after controlling for age, education, socioeconomic status, traditional Japanese food consumption, pulmonary function, apolipoprotein E4, proficiency in speaking Japanese, and other possible confounders. When data were analyzed separately for subgroups according to the language preferred at testing (English or Japanese), associations between childhood years in Japan and CASI scores were in opposite directions negative for the group tested in English and positive for the group tested in Japanese. The interaction between the testing language and childhood years in Japan was statistically significant. CONCLUSIONS: There was an inverse association between years spent in Japan during school-age years of childhood and cognitive test performance in late life. This association could not be accounted for by age, education, or other confounding factors. However, this finding was not observed in participants who preferred being tested in Japanese. To assess cognitive test performance in older people, it is of prime importance to use the most optimal language for testing, usually the subject's native language. J Am Geriatr Soc 48: 199–204, 2000.

Objectives To describe the effects of age and education for the Cognitive Abilities Screening Instrument (CASI), a 25-item test of cognitive function. Design Cross-sectional descriptive study of the initial enrollment in a community-based prospective cohort study. Participants A total of 2524 cognitively intact older adults over age 65 who were members of a major health maintenance organization, and who consented to participate in a longitudinal study. Measurements Summary scores for the CASI are given in the form of mean, median and percentile distributions specific for age and educational level. Results Based upon maximum likelihood analyses, age and education were significant (p Conclusions Like most cognitive screening instruments, performance on the CASI in non-demented persons is influenced by age and education. The reference values for 5-year age categories described in this article should be useful for clinicians and research investigators when using the CASI as a measure of cognitive function.

memory, the Neuropsychological Assessment Battery (NAB) List Learning (LL) test (Stern & White, 2003) is a promising tool for the assessment of older adults due to its relative simplicity, excellent psychometric validation, equivalent forms, and extensive normative data in older individuals. This study examined the diagnostic utility of the NAB LL test in differentiating cognitively normal, MCI, and AD participants. Methods: Extant data from the Boston University Alzheimer’s Disease Center Registry was retrospectively analyzed for 153 participants (57-94 years, 74 8 years; 61% women) diagnosed by a consensus team as cognitively normal (n 98), amnestic MCI (single or multiple domain; n 29), or AD (n 26). Diagnoses were made independent of NAB LL performance. To determine classification accuracy, receiver operating characteristics analyses were conducted for seven NAB LL variables (List A Immediate Recall, List B Immediate Recall, Short Delay Recall, Long Delay Recall, Percent Retention, and Recognition Hits and False Alarms). In addition, ordinal multiple regression was used to create a model to predict group membership based on a combination of the NAB LL variables. Results: The sensitivities and specificities of the NAB LL test variables were good to excellent, yielding positive likelihood ratios ranging from 1.8 to 30.2 (Mdn 4.2). The ordinal regression produced a model that predicted group membership with an overall accuracy of 85%. The model was most accurate at classifying controls (97%), followed by AD (74%) and MCI (52%), which indicates that it can very accurately rule out the latter two diagnoses. Conclusions: Both the regression-based model and the individual NAB LL variables were highly accurate in differentiating cognitively normal controls, MCI, and AD groups. Compared to published data, the classification accuracy statistics presented here appear to match or exceed those reported for other common list learning tests (e.g., HVLT-R, CERAD, CVLT) in this population.