Jee Wook Kim

Alcohol and Cognition in the Elderly: A Review

Consumption of large amounts of alcohol is known to have negative effects, but consumption in smaller amounts may be protective. The effect of alcohol may be greater in the elderly than in younger adults, particularly with regard to cognition. However, the drinking pattern that will provide optimal protection against dementia and cognitive decline in the elderly has not been systematically investigated. The present paper is a critical review of research on the effect of alcohol on cognitive function and dementia in the elderly. Studies published from 1971 to 2011 related to alcohol and cognition in the elderly were reviewed using a PubMed search. Alcohol may have both a neurotoxic and neuroprotective effect. Longitudinal and brain imaging studies in the elderly show that excessive alcohol consumption may increase the risk of cognitive dysfunction and dementia, but low to moderate alcohol intake may protect against cognitive decline and dementia and provide cardiovascular benefits. Evidence suggesting that low to moderate alcohol consumption in the elderly protects against cognitive decline and dementia exists; however, because of varying methodology and a lack of standardized definitions, these findings should be interpreted with caution. It is important to conduct more, well-designed studies to identify the alcohol drinking pattern that will optimally protect the elderly against cognitive decline and dementia.

Microstructural alteration of the anterior cingulum is associated with apathy in Alzheimer disease.

OBJECTIVES To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD). DESIGN Cross-sectional study. SETTING University Dementia Clinic. PARTICIPANTS Fifty-one very mild or mild probable AD subjects. INTERVENTION Volumetric magnetic resonance imaging with diffusion tensor imaging. MEASUREMENTS Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory. RESULTS Apathy group showed significantly lower FA values than apathy-free group in the left anterior cingulum (A-C), regardless of concomitant depression and psychotropic medications. Left A-C FA values also had significant linear relationship with apathy-composite scores as a measure of apathy severity, even after controlling gray matter density of the ipsilateral anterior cingulate cortex. CONCLUSIONS Our findings support that communication failure between the anterior cingulate cortex and other brain structures via the A-C contributes to the development and aggravation of apathy in AD, additionally supporting the general notion of disconnection syndrome for clinical manifestation of AD.

Total Scores of the CERAD Neuropsychological Assessment Battery: Validation for Mild Cognitive Impairment and Dementia Patients With Diverse Etiologies

OBJECTIVES This study aimed to validate the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer Disease neuropsychological battery (CERAD-NP) for a large elderly population including mild cognitive impairment (MCI) and dementia patients with various etiologic backgrounds. The authors also investigated whether the addition of frontal-executive function score can improve the discrimination accuracy of the total scores for dementia and MCI. DESIGN, SETTING, AND PARTICIPANTS One thousand three hundred thirty-six normal comparison (NC), 583 dementia (420 AD, 111 non-AD dementia, and 52 mixed AD with non-AD dementia), and 250 MCI (223 amnestic and 27 nonamnestic MCI) individuals living in the community were included (all aged 60 years and older). RESULTS Both TS-I and TS-II were highly correlated with other global cognitive and functional scales. Both total scores showed, though modest, superior NC versus MCI discrimination ability to Mini-Mental State Examination (MMSE). Their discrimination ability for NC versus dementia was excellent and significantly better, especially in discriminating very mild dementia, than MMSE. The addition of frontal-executive test score to TS-I or TS-II did not make a significant improvement in dementia or MCI discrimination ability. Both of them also showed higher test-retest and interrater reliability than MMSE or any individual neuropsychological tests in the CERAD-NP. CONCLUSION These results strongly support the validity and usefulness of CERAD total scores for early detection and progression monitoring of MCI and dementia in clinical and research settings.

Validity of the telephone interview for cognitive status (TICS) and modified TICS (TICSm) for mild cognitive imparment (MCI) and dementia screening

This study aimed to validate the TICS and modified TICS (TICSm) in Korean elderly population and to compare MCI and dementia screening ability between TICS and TICSm. TICS and TICSm were administered to 70 cognitively normal (CN), 75 MCI, and 85 dementia subjects, with mini-mental state examination (MMSE) and other cognitive and functional measures. TICS and TICSm scores were highly correlated with other global cognitive and functional scores. The CN vs. dementia discrimination ability of both instruments was as excellent as that of MMSE (sensitivity/specificity at optimal cutoff: 87.1/90.1 for TICS; 88.2/90.0 for TICSm). Although their CN vs. MCI discrimination performances were comparable to that of MMSE, they were far from perfect (sensitivity/specificity: 69.3/68.6 for TICS; 73.3/67.1 for TICSm). There was no significant difference in dementia or MCI screening accuracy between TICS and TICSm. Both of them also showed high test-retest reliability. Our findings indicate that TICS and TICSm are reliable and as valid as MMSE in regard of screening cognitively impaired elderly. In terms of the comparison between TICSm and TICS, however, TICSm has little advantage over TICS for screening dementia and even MCI, in spite of longer administration time and more efforts required.

Relationship of Amyloid-Beta Burden With Age-At-Onset in Alzheimer Disease

OBJECTIVE To investigate the relationship between in vivo brain amyloid-beta (Aβ) burden, measured by C-labeled Pittsburgh Compound B (C-PiB) retention, and age-at-onset in patients with Alzheimer disease (AD). DESIGN Cross-sectional study. SETTING University Dementia Clinic. PARTICIPANTS Twenty-two AD patients including 11 early-onset AD (EOAD: onset <65 years) and 11 late-onset AD (LOAD: onset ≥65years) cases with matched dementia severity, duration of illness, and apolipoprotein E ε4 allele number. INTERVENTION C-PiB positron emission tomography scans. MEASUREMENTS Both region of interest and voxel-based analyses were performed to compare C-PiB retention between EOAD and LOAD groups, and to test linear relationship between age-at-onset and C-PiB retention. RESULTS Both region of interest (ROI) and voxel-based analyses revealed that EOAD patients had significantly higher C-PIB retentions than LOAD patients in diffuse brain regions including frontal, lateral parietal, lateral temporal, and occipital cortex, and basal ganglia. Subgroup analyses showed that negative correlation between age-at-onset and C-PiB retention was significant in LOAD but not in EOAD. CONCLUSIONS Our finding of a heavier Aβ burden in the brain of living EOAD patients than LOAD patients is in agreement with those from postmortem studies. The inverse relationship between age-at-onset and Aβ burden is possibly associated with aging-related decrease of brain or cognitive reserve and with aging-related increase of brain vulnerability.

A Normative Study of the Digit Span in an Educationally Diverse Elderly Population

Objective The purpose of this study was to explore the effect of demographic variables on Digit Span test (DS) performance in an educationally diverse elderly population and to provide normative information. Methods The DS was administered to 784 community-dwelling volunteers aged 60-90 years with an educational history of from zero to 25 years of full-time education. People with serious neurological, medical and psychiatric disorders (including dementia) were excluded. Results Age, education and gender were found to be significantly associated with performance on the DS. Based on the results obtained, DS norms were stratified by age (2 strata), education (3 strata), and gender (2 strata). Conclusion Our results on DS performance suggest that both attention and working memory are influenced by age, education and gender. The present study provides reasonably comprehensive normative information on the DS for an educationally diverse elderly population.

Improvement of Dementia Screening Accuracy of Mini-Mental State Examination by Education-Adjustment and Supplementation of Frontal Assessment Battery Performance

This study aimed to investigate whether the demographic variable-adjustment and supplementation of Frontal Assessment Battery (FAB) score can improve the screening ability of Mini-Mental State Examination (MMSE) for dementia and its subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia (320 Alzheimers disease [AD]; 139 non-Alzheimers disease dementia [NAD]; and 15 mixed AD-NAD dementia) individuals living in the community were included. Education-adjusted MMSE (MMSE-edu) score showed significantly better screening accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not for overall dementia and AD, than MMSE raw score alone. Additional supplementation of FAB to MMSE-edu further increased the ability for overall dementia or NAD screening, but not for AD screening. Further education adjustment of MMSE-FAB also improved its ability for overall dementia, AD, and NAD screening. These results strongly support the usefulness of education-adjustment and supplementation of frontal function assessment to improve screening performance of MMSE for dementia and its subtypes, NAD in particular.

Comparison of Regional Gray Matter Atrophy, White Matter Alteration, and Glucose Metabolism as a Predictor of the Conversion to Alzheimer's Disease in Mild Cognitive Impairment

We compared the predictive ability of the various neuroimaging tools and determined the most cost-effective, non-invasive Alzheimers disease (AD) prediction model in mild cognitive impairment (MCI) individuals. Thirty-two MCI subjects were evaluated at baseline with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, diffusion tensor imaging (DTI), and neuropsychological tests, and then followed up for 2 yr. After a follow up period, 12 MCI subjects converted to AD (MCIc) and 20 did not (MCInc). Of the voxel-based statistical comparisons of baseline neuroimaging data, the MCIc showed reduced cerebral glucose metabolism (CMgl) in the temporo-parietal, posterior cingulate, precuneus, and frontal regions, and gray matter (GM) density in multiple cortical areas including the frontal, temporal and parietal regions compared to the MCInc, whereas regional fractional anisotropy derived from DTI were not significantly different between the two groups. The MCIc also had lower Mini-Mental State Examination (MMSE) score than the MCInc. Through a series of model selection steps, the MMSE combined with CMgl model was selected as a final model (classification accuracy 93.8%). In conclusion, the combination of MMSE with regional CMgl measurement based on FDG-PET is probably the most efficient, non-invasive method to predict AD in MCI individuals after a two-year follow-up period. Graphical Abstract

The Effectiveness of Continuing Group Psychotherapy for Outpatients with Alcohol Dependence: 77‐Month Outcomes

BACKGROUND Group psychotherapy (PT) is one of the most common interventions used to treat alcohol dependence (AD), and it is assumed to be effective. Despite its common clinical use, long-term trials that have been conducted to examine the efficacy of group PT in the treatment of outpatients with AD are limited and often lack appropriate comparisons. On that basis, a long-term comparative trial was performed with the main objective of evaluating the effectiveness of continuing group PT for outpatients with AD. METHODS Quasi-experimental trial was conducted from January 2004 to May 2010 in 177 AD subjects who had completed an inpatient 10-week alcohol treatment program. Abstinence rates of the combined group (experimental group: outpatient individual PT plus group PT, N = 94) and the standard outpatient individual PT-only group (comparison group, N = 83) were statistically compared using Kaplan-Meier survival analysis. Predictive factors of abstinence rate for alcohol were assessed using Cox regression analysis. RESULTS Abstinence rates of the combined PT group were significantly high relative to those of the outpatient individual PT-only group. Significant predictive factors for the alcohol abstinence rate were outpatient group PT and age. Even after controlling for confounding factors, outpatient group PT was a significant predictive factor for the alcohol abstinence rate. CONCLUSIONS Our findings indicate that for AD patients who had completed an inpatient 10-week alcohol treatment, outpatient group PT appears to be an effective form of continuing care or aftercare within the context of an outpatient service delivery system.

The 5-item Alcohol Use Disorders Identification Test (AUDIT-5): An Effective Brief Screening Test for Problem Drinking, Alcohol Use Disorders and Alcohol Dependence

AIMS To identify an optimal brief version of the Alcohol Use Disorders Identification Test (AUDIT) and to evaluate its effectiveness as a screening test for problem drinking (PD), alcohol use disorders (AUD) and alcohol dependence (AD). METHODS A multicenter trial was conducted from March, 2010, to January, 2012, in 101 normal comparison, 203 risky drinking, 92 alcohol abuse and 101 AD men aged below 65 years of age in a Korean population. For the purposes of screening, risky drinking, alcohol abuse and AD were grouped: all the three grouped as PD and the latter two grouped as AUD. Logistic regression analysis was used to determine the items among the 10-item AUDIT that provided information predictive of PD, AUD and AD. Receiver operating characteristic (ROC) curve analysis was performed to investigate the discrimination ability of the brief versions of AUDIT, 10-item AUDIT and Cut-down, Annoyed, Guilt, Eye-opener as a screen for PD, AUD and AD. Areas under the ROC curve were compared between tests according to the method suggested by Hanley and McNeil. RESULTS The 5-item AUDIT (AUDIT-5: AUDIT items 2, 4, 5, 9 and 10) was obtained by stepwise multiple regression analyses for each screening. AUDIT-5 exhibited an AUD screening accuracy significantly superior to that of the 10-item AUDIT, but other brief versions of AUDIT and CAGE did not. Furthermore, AUDIT-5 had a high PD and AD screening accuracy equivalent to that of the 10-item AUDIT. CONCLUSION These results strongly support the usefulness of AUDIT-5 for screening of PD, AUD and AD in clinical settings in Korean male populations.