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L5, the most electronegative subfraction of low-density lipoprotein cholesterol (LDL-C), may play a role in the pathogenesis of cerebrovascular dysfunction and neurodegeneration. We hypothesized that serum L5 is associated with cognitive impairment and investigated the association between serum L5 levels and cognitive performance in patients with mild cognitive impairment (MCI). This cross-sectional study conducted in Taiwan included 22 patients with MCI and 40 older people with normal cognition (healthy controls). All participants were assessed with the Cognitive Abilities Screening Instrument (CASI) and a CASI-estimated Mini-Mental State Examination (MMSE-CE). We compared the serum total cholesterol (TC), LDL-C, and L5 levels between the MCI and control groups and examined the association between lipid profiles and cognitive performance in these groups. The serum L5 concentration and total CASI scores were significantly negatively correlated in the MCI group. Serum L5% was negatively correlated with MMSE-CE and total CASI scores, particularly in the orientation and language subdomains. No significant correlation between the serum L5 level and cognitive performance was noted in the control group. Conclusions: Serum L5, instead of TC or total LDL-C, could be associated with cognitive impairment through a disease stage-dependent mode that occurs during neurodegeneration.

The component of working memory that the frontal cortex subserves is frequently characterized as the executive working memory (EWM). This study applied a neuropsychological measure of EWM (NPM-EWM) in older adults with memory impairment to investigate the EWM. Thirty-two older adults from the community were recruited as older healthy controls (OHCs), and 58 older adults from a memory clinic were diagnosed with mild cognitive impairment (MCI) and mild dementia (MD). Significant differences were found among the three groups in the Clinical Dementia Rating (CDR), the Chinese version of Mini-Mental State Examination (MMSE-C), and the Cognitive Abilities Screening Instrument (CASI). The NPM-EWM was applied by using the learning task of the Comprehensive Nonverbal Memory Test Battery, where the 7 scores were divided into two categories: mnemonic capacity and executive error. All OHCs, more than 50% MCI, and less than 25% of MD patients passed the NPM-EWM. The MCI-passed and MD-passed subgroups showed similar mnemonic capacity and executive errors, and both the subgroups had significantly worse performance than the OHC group. The MD-passed subgroup had a higher Hamilton Depression Rating Scale (HDRS) score than did the MD-failed subgroup. The MCI-failed subgroup had a higher Hierarchy of Care Required (HCR) level in instrumental activities of daily living (IADL) than did the MCI-passed subgroup. These findings indicated that applying the NPM-EWM for older adults with memory impairment may offer precise and tailored care to a whole person, especially for the MCI patients with poorer EWM and the MD patients with relatively intact EWM.

Background The rate of undetected dementia is high in China. However, the performance of dementia screening tools may differ in the Chinese population due to the lower education level and cultural diversity. This study aimed to evaluate the diagnostic accuracy of dementia screening tools in the Chinese population. Methods Eleven electronic databases were searched for studies evaluating the diagnostic accuracy of dementia screening tools in older Chinese adults. The overall diagnostic accuracy was estimated using bivariate random-effects models, and the area under the summary receiver operating characteristic curve was presented. Results One hundred sixty-seven studies including 81 screening tools were identified. Only 134 studies qualified for the meta-analysis. The Mini-Mental State Examination (MMSE) was the most commonly studied tool, with a combined sensitivity (SENS) and specificity (SPEC) of 0.87 (95%CI 0.85–0.90) and 0.89 (95%CI 0.86–0.91), respectively. The Addenbrooke’s Cognitive Examination-Revised (ACE-R) (SENS: 0.96, 95%CI 0.89–0.99; SPEC: 0.96, 95%CI 0.89–0.98) and Montreal Cognitive Assessment (MoCA) (SENS: 0.93, 95%CI 0.88–0.96; SPEC: 0.90, 95%CI 0.86–0.93) showed the highest performance. The General Practitioner Assessment of Cognition (GPCOG), Hasegawa’s Dementia Scale and Cognitive Abilities Screening Instrument had performances comparable to that of the MMSE. The cut-off scores ranged widely across studies, especially for the MMSE (range: 15–27) and MoCA (range: 14–26). Conclusions A number of dementia screening tools were validated in the Chinese population after cultural and linguistical adaptations. The ACE-R and MoCA had the best diagnostic accuracy, whereas the GPCOG, with an administration time

Objective:The Cognitive Abilities Screening Instrument (CASI) is a screening test of global cognitive function used in research and clinical settings. However, the CASI was developed using face validity and has not been investigated via empirical tests such as factor analyses. Thus, we aimed to develop and test a parsimonious conceptualization of the CASI rooted in cognitive aging literature reflective of crystallized and fluid abilities.Design:Secondary data analysis implementing confirmatory factor analyses where we tested the proposed two-factor solution, an alternate one-factor solution, and conducted a χ2 difference test to determine which model had a significantly better fit.Setting:N/A.Participants:Data came from 3,491 men from the Kuakini Honolulu-Asia Aging Study.Measurements:The Cognitive Abilities Screening Instrument.Results:Findings demonstrated that both models fit the data; however, the two-factor model had a significantly better fit than the one-factor model. Criterion validity tests indicated that participant age was negatively associated with both factors and that education was positively associated with both factors. Further tests demonstrated that fluid abilities were significantly and negatively associated with a later-life dementia diagnosis.Conclusions:We encourage investigators to use the two-factor model of the CASI as it could shed light on underlying cognitive processes, which may be more informative than using a global measure of cognition.

Although heavy alcohol consumption has been identified as a risk factor for adverse cognitive functioning, it currently remains unclear whether moderate alcohol consumption exerts similar effects. Observational studies previously reported the potential benefits of moderate alcohol consumption on cognition, particularly in the elderly; however, these effects have not yet been demonstrated in Asian populations. The aim of the present study was to investigate the relationship between alcohol consumption levels and global and domain-specific cognitive functions in cognitively intact elderly Japanese men. Cross-sectional data from the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA), an ongoing prospective, population-based study in Shiga, Japan, were used to examine the relationship between alcohol consumption and cognitive function. Men (n = 585) aged ≥65 years provided information on their weekly consumption of alcohol, and the data obtained were used to construct categories of never, ex- (quit before interview), very light (14 g/day), light (14-23 g/day), moderate (23-46 g/day), and heavy (46 g/day) drinkers. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). A fractional logistic regression model adjusted for age, education, body mass index, smoking, exercise, hypertension, diabetes, and dyslipidemia showed that the CASI scores for global and domain-specific cognitive functions were not significantly different between all subgroups of current drinkers and never-drinkers. However, the CASI score of ex-drinkers (multivariable adjusted mean CASI score [SD]) was significantly lower than that of never-drinkers in the global [never vs. ex: 90.16 (2.21) vs. 88.26 (2.58)] and abstraction and judgment domain [never vs. ex: 9.48 (0.46) vs. 8.61 (0.57)]). The present results do not suggest any beneficial or adverse relationship between current alcohol consumption levels and cognitive functioning (both global and domain specific) in elderly Japanese men; however, low cognitive function among ex-drinkers warrants future investigations to identify the factors causing drinkers to quit.

Background Cognitive impairment is a public health burden. Our objective was to investigate associations between work hours and cognitive function. Methods Multi-Ethnic Study of Atherosclerosis (MESA) participants (n = 2,497; 50.7% men; age range 44–84 years) reported hours per week worked in all jobs in Exams 1 (2000–2002), 2 (2002–2004), 3 (2004–2005), and 5 (2010–2011). Cognitive function was assessed (Exam 5) using the Cognitive Abilities Screening Instrument (version 2), a measure of global cognitive functioning; the Digit Symbol Coding, a measure of processing speed; and the Digit Span test, a measure of attention and working memory. We used a prospective approach and linear regression to assess associations for every 10 hours of work. Results Among all participants, associations of hours worked with cognitive function of any type were not statistically significant. In occupation-stratified analyses (interaction p = 0.051), longer work hours were associated with poorer global cognitive function among Sales/Office and blue-collar workers, after adjustment for age, sex, physical activity, body mass index, race/ethnicity, educational level, annual income, history of heart attack, diabetes, apolipoprotein E-epsilon 4 allele (ApoE4) status, birth-place, number of years in the United States, language spoken at MESA Exam 1, and work hours at Exam 5 (β = –0.55, 95% CI = –0.99, –0.09) and (β = –0.80, –1.51, –0.09), respectively. In occupation-stratified analyses (interaction p = 0.040), we also observed an inverse association with processing speed among blue-collar workers (adjusted β = –0.80, –1.52, –0.07). Sex, race/ethnicity, and ApoE4 did not significantly modify associations between work hours and cognitive function. Conclusion Weak inverse associations were observed between work hours and cognitive function among Sales/Office and blue-collar workers.

Objectives: The Clinical Dementia Rating (CDR) Scale is the gold standard for the staging of dementia due to Alzheimer's disease (AD). However, the application of CDR for the staging of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in AD remains controversial. This study aimed to use the sum of boxes of the CDR (CDR-SB) plus an SCD single questionnaire to operationally determine the different stages of cognitive impairment (CI) due to AD and non-AD.Methods: This was a two-phase study, and we retrospectively analyzed the Show Chwan Dementia registry database using the data selected from 2015 to 2020. Individuals with normal cognition (NC), SCD, MCI, and mild dementia (MD) due to AD or non-AD with a CDR < 2 were included in the analysis.Results: A total of 6,946 individuals were studied, including 875, 1,009, 1,585, and 3,447 with NC, SCD, MCI, and MD, respectively. The cutoff scores of CDR-SB for NC/SCD, SCD/MCI, and MCI/dementia were 0/0.5, 0.5/1.0, and 2.5/3.0, respectively. The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values of the test groups were 0.85, 0.90, and 0.92 for discriminating NC from SCD, SCD from MCI, and MCI from dementia, respectively. Compared with the Cognitive Abilities Screening Instrument or the Montreal Cognitive Assessment, the use of CDR-SB is less influenced by age and education.Conclusion: Our study showed that the operational determination of SCD, MCI, and dementia using the CDR-SB is practical and can be applied in clinical settings and research on CI or dementia.

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/Aims: To detect cognitive decline in older adults, measures of verbal fluency and verbal memory are widely used. Less is known about performance in these measures in younger persons or according to education level and gender. We investigated cognitive performance according to age, education and gender among cognitively healthy adults aged 30–100 years. Methods: The study population comprised 4,174 cognitively healthy persons participating in the nationally representative Finnish Health 2011 survey. Cognitive assessment included verbal fluency, word list memory, word list recall and word list savings from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery. Results: Total variance in the cognitive test performance explained by age, education and gender varied from 12.3 to 31.2%. A decreasing trend in cognitive performance existed in all subtests by advancing age, with differences appearing between 50 and 55 years. Persons with the highest-education level performed best for all measures. For the participants < 55 years, education explained part of the variance, while age and gender did not. Conclusions: When assessing cognition, age and education should be accounted for in more detail in research and clinical practice. Additionally, the cohort effect and its potential impact on the renewal cycle of future normative values for cognitive tests should be considered.

Background: The aim of this study is to investigate the validity of the coin-in-the-hand (CIH) test with other neuropsychological tests for the detection of malingering in the memory. Materials and Methods: A simulated scenario design was developed to investigate the validity of the CIH test, entitled the Test of Memory Malingering (TOMM), associated with the Clinical Dementia Rating, the cognitive abilities screening instrument, the Mini-Mental Status Examination, and the WHO Quality of Life-BREF. The performances of the patients with dementia (n = 25) were compared with one group of normal controls (n = 9), and another group instructed to simulate malingering dementia (n = 19). Results: The CIH test demonstrated good validity and displayed a better sensitivity and a positive likelihood ratio than the TOMM, while patients with dementia could provide, on average, more than nine correct answers, in comparison to only more than six correct answers in the simulated malingering group. The optimal cutoff score of the CIH test is ≤8. Conclusions: This pilot study showed that the CIH test is a quick and practical test for detecting malingering in the memory.

Background: The Cognitive Abilities Screening Instrument (CASI) is increasingly used to assess general cognitive function in people with dementia. The Mini-Mental State Examination (MMSE) score can be converted from the CASI (i.e., the estimated MMSE). Recognizing that measurement equivalence is critical to meaningfully representing one with the other, we aimed to determine whether the estimated MMSE score obtained from the CASI was equivalent to the original MMSE in people with dementia. Methods: We obtained 110 data points for the MMSE and CASI scores in people with dementia. The intraclass correlation coefficient (ICC), Pearson’s r, percent of standard error of measurement (SEM%), paired t-test, and effect size (Cohen’s d) were used to investigate the equivalence. Results: To examine the equivalence between the original and estimated MMSE score, the ICC and Pearson’s r of the total score and six domains were 0.62–0.95 and 0.62–0.96, respectively. The SEM% of the total score and six domains were 0.6–8.9%. The paired t-test results showed a significant difference (p &lt, 0.05) between the total score and the three domains. The Cohen’s d of the total score and six domains were 0.06–0.27. Conclusions: The estimated MMSE score was found to have moderate to excellent equivalence to the original MMSE score. The three domains (i.e., registration, attention and calculation, and visual-constructional ability) with moderate equivalence should be used cautiously to interchange with the original MMSE in people with dementia.

Introduction As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear. Materials and Methods We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC. Results Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): −0.042 (−0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer’s disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness. Conclusions Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults.

Wafaa M Farghaly,1 Hamdy N El Tallawy,1 Heba Mohamed,1 Sara H El Tallawy,2 Mohamed A Abdelhamed1 1Department of Neuropsychiatry, and Neuroepidemiology Lab, Faculty of Medicine, Assiut University, Assiut, Egypt; 2Department of Psychology, Faculty of Arts, Assiut University, Assiut, EgyptCorrespondence: Mohamed A AbdelhamedDepartment of Neuropsychiatry, and Neuroepidemiology research center, Faculty of medicine, Assiut University, 7th Floor, Assiut, 71926, EgyptTel +00201002629734Fax +20 88 2333327Email moh78_abdelhamed@aun.edu.egPurpose: Validated diagnostic scales for dementia in Arabic are still scarce. The aim of this study is to construct a standardized dementia scale for dementia diagnosis among the Arabic-speaking population.Patients and Methods: Construction of the Dementia Arabic Scale (DAS) was done, followed by evaluation of content validity. A pilot study was done to ascertain feasibility and language clarity used in the scale. Patients diagnosed to have major neurocognitive disorder according to DSM-V criteria and control group were subjected to DAS, mini-mental state examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Finally, standardization of the scale and estimation of cutoff point, sensitivity, specificity, positive predictive value and negative predictive value of the newly constructed scale (DAS) were done.Results: There is significant correlation between DAS and both MMSE and CASI on Pearson’s correlation study. The internal consistency of the DAS scale was good, with Cronbach’s alpha correlation coefficient of 0.88. At cut-off ≤ 95 for literate, and ≤ 68 for illiterate, the sensitivity of the DAS scale was 100%, 87% for literate and illiterate, respectively, while specificity was 84%, 96% respectively, with an area under the receiver operating characteristic curve of (AUC) 0.96.Conclusion: The DAS scale is an acceptable, reliable and valid scale for the diagnosis of dementia in Arabic-speaking countries.Keywords: dementia, cognitive screening test, standardization, validity

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.

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.

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.

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.

Background We examined whether changes in metabolic factors over 10 years were associated with cognitive performance. Methods Participants from the Multi-Ethnic Study of Atherosclerosis were followed since baseline (2000–2002) with five clinical examinations. At exam 5 (2010–2012), they received a short cognitive battery (Cognitive Abilities Screening Instrument [CASI], Digit Symbol Coding [DSC], and Digit Span [DS]). We examined associations between baseline metabolic factors and their changes over time before cognitive testing. Results Among 4392 participants, baseline metabolic disorders (fasting glucose, systolic and diastolic blood pressures) were significantly associated with poorer CASI, DSC, and DS scores measured 10 years later. Increases in blood pressure were associated with lower cognitive performance. Results did not differ by race/ethnicity and were stronger among those without the APOE e4 allele. Conclusions Cognitive performance was associated with antecedent abnormalities in glucose metabolism and blood pressure increases. Findings appeared stronger among APOE e4-negative participants.

Background Findings are inconsistent regarding the role of traumatic head injury in the subsequent development of neurologic outcomes. Objective Examine the relationship between head injury and later cognitive impairment. Methods A sample of 3,123 Japanese-American men was assessed for history of head injury and evaluated for cognitive impairment using the Cognitive Abilities Screening Instrument (CASI). For a subsample of 676 respondents, neuropathologic results from those with and without head injury were compared. Results Although the crude model showed an association between history of head injury and later severe cognitive impairment, the relationship lost significance in the adjusted model (OR = 1.320, CI: 0.90-1.93), regardless of time between injury and impairment. Similar to cognitive impairment, hippocampal sclerosis was observed significantly more in the brains of respondents with a history of head injury in the crude model, but the relationship weakened in the adjusted model (OR = 1.462, CI: 0.68-3.12). After adjustment, decedents with a head injury demonstrated marginally higher brain weight (OR = 1.003, CI: 1.00-1.01). Conclusion We did not find a relationship between head injury and subsequent cognitive decline in this cohort. The neuropathology results also displayed no strong association between history of head injury and specific brain lesions and characteristics. These results support other findings in prospective cohorts. However, they could be influenced by the demographic make-up of the sample (male Japanese-Americans) or by the observation that the majority reported only a single head injury.

Objectives Visuospatial dysfunction (VSD) is one of the most important symptoms for the diagnosis of dementia with Lewy bodies (DLB). The aim of this study was to validate a novel VSD questionnaire and determine the cutoff score for the screening for VSD in DLB. Methods This is a retrospective analysis of data from a project of the History-based Artificial Intelligent Clinical Dementia Diagnostic System (HAICDDS). VSD of non-demented control (NDC), Alzheimer's disease (AD), and DLB participants were analyzed and compared using the visuospatial questionnaire in the HAICDDS (HAI-VSQ), the Draw subscale in the Cognitive Abilities Screening Instrument (CASI-Draw), and the visuospatial subscale in Montreal Cognitive Assessment (MoCA-VS). Results A total of 440 individuals were studied, including 154 NDC, 229 AD, and 57 DLB participants. Compared to NDC or AD participants, DLB participants showed a higher total score on HAI-VSQ after adjustment for age. Using HAI-VSQ, a cutoff score ≥ 2 was useful for the screening for VSD in DLB with a sensitivity of 0.77 and a specificity of 0.94. Compared with CASI-Draw or MoCA-VS, HAI-VSQ was least influenced by gender, age, and education and had the highest correlation with the sum of boxes of the Clinical Dementia Rating scale. After adjustment for age, education, gender, and global cognitive function, HAI-VSQ significantly discriminated DLB from AD and NDC whereas MoCA-VS or CASI-Draw did not. Conclusion Our study showed that the newly designed simple questionnaire was a practical screening tool for VSD in DLB that can be applied in clinical practice as well as on a registration platform.

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.

Introduction: A positive association between physical activity and cognition has been reported. However, very few pertinent studies have evaluated physical activity by objective measures. Hypothesis: In a community-based sample of non-demented men, objectively measured step count was positively associated with higher cognitive function. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited community-dwelling apparently healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer (DIGI-Walker, DW-200) at baseline (2006-08). Among 853 mem who returned for follow-up (2010-12), we assessed their cognition using Cognitive Abilities Screening Instrument (CASI) score. The score can range from 0 to 100, and higher score indicates better cognition. We restricted our analyses to those with a valid 7-day average step count at baseline and who remained free of stroke (N=678). We calculated crude and adjusted mean CASI score according to quartile of average step count using linear regression models. All adjusting covariates used in models were asssessed at baseline including age, educational attainment, smoking, and drinking. Results: The mean [standard deviation] of age and unadjusted score were 63.8 [9.1] years and 90.8 [5.8]. Mean CASI score was higher in higher quartile of average step: 90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile of average step ( P for trend =0.004) in a model adjusted for age and education. Further adjustment for smoking, drinking and other cardiovascular risk factors resulted in similar pattern of association (Table 1). Conclusions: Apparently healthy Japanese men with greater 7-day average step count at baseline measured with pedometer was associated with a small but significantly higher CASI score than those with fewer step count. The finding is consistent with the hypothesis that physical activity is protective for cognition in non-demented individuals.

The problem of population aging in Taiwan is getting worse, the diseases of elderly patients are considered as an important issue. Dementia, one of brain diseases for elderly people, is a degeneration of brain. The main symptom of Dementia is the deterioration of memory and some cognitive functions, which eventually leads to the complete loss of mental function and death. Dementia will not only seriously affect the normal life, but also cause great burdens on relatives and society. Eventually, patients will completely lose mental functions. Therefore, diagnosis and treatment of dementia will be an important issue in medical research.The data were obtained from medical center based on the Cognitive Abilities Screening Instrument (CASI) test. Data discretization and Synthetic minority over-sampling technique were used to pre-processing this data. Then, Classification and Regression Tree (CART) and Chi-Square Automatic Interaction Detector (CHAID) tree-based algorithms were used to classify this data. As the result of decision tree, age is an important factor which affects brain diseases for elderly people.