Shu-Ing Chang

Cognitive and behavioral effects of quetiapine in Alzheimer Disease patients

In a prospective, open-label, 12-week pilot study in outpatients with probable Alzheimer disease (AD) with psychosis or aggressive behaviors, we used the Alzheimers Disease Assessment Scale–cognitive subscale (ADAS-cog) and the Neuropsychiatric Inventory (NPI) to evaluate the cognitive and behavioral effects of quetiapine. After receiving doses ranging from 50 to 150 mg, patients given quetiapine showed a significant decrease of delusions, aggression, and overall behaviors based on NPI scores at 6 and 12 weeks. ADAS-cog scores did not show a significant change over 12 weeks. This study provides initial evidence that quetiapine does not significantly worsen cognition in AD outpatients.

Self-administered Gerocognitive Examination (SAGE) A Brief Cognitive Assessment Instrument for Mild Cognitive Impairment (MCI) and Early Dementia

ObjectivesTo develop a self-administered cognitive assessment instrument to facilitate the screening of mild cognitive impairment (MCI) and early dementia and determine its association with gold standard clinical assessments including neuropsychologic evaluation. MethodsAdults aged above 59 years with sufficient vision and English literacy were recruited from geriatric and memory disorder clinics, educational talks, independent living facilities, senior centers, and memory screens. After Self-administered Gerocognitive Examination (SAGE) screening, subjects were randomly selected to complete a clinical evaluation, neurologic examination, neuropsychologic battery, functional assessment, and mini-mental state examination (MMSE). Subjects were identified as dementia, MCI, or normal based on standard clinical criteria and neuropsychologic testing. ResultsTwo hundred fifty-four participants took the SAGE screen and 63 subjects completed the extensive evaluation (21 normal, 21 MCI, and 21 dementia subjects). Spearman rank correlation between SAGE and neuropsychologic battery was 0.84 (0.76 for MMSE). SAGE receiver operating characteristics on the basis of clinical diagnosis showed 95% specificity (90% for MMSE) and 79% sensitivity (71% for MMSE) in detecting those with cognitive impairment from normal subjects. ConclusionsThis study suggests that SAGE is a reliable instrument for detecting cognitive impairment and compares favorably with the MMSE. The self-administered feature may promote cognitive testing by busy clinicians prompting earlier diagnosis and treatment.

A pilot open-label trial of citalopram for restless activity and aberrant motor behaviors in alzheimer disease

OBJECTIVE In a prospective, open-label pilot study in probable-Alzheimer disease (AD) outpatients, the authors investigated the efficacy of citalopram to reduce restless activity and aberrant motor behaviors. METHODS Nineteen subjects were evaluated with Neuropsychiatric Inventory subscale and total scores. RESULTS There was a significant decline in aberrant motor behaviors and overall behavior problems at 4, 8, and 12 weeks. CONCLUSION This study provides initial evidence that citalopram may be effective in reducing aberrant motor behaviors in AD. However, because of the potential biases of an open-label study, these findings need to be confirmed in a larger, controlled trial.

Memory profiles differ between parkinsonian dementia syndromes and Alzheimer's disease

efits, and general ethics of disclosing apolipoprotein (APOE) genotype to older adults. Knowledge that one carries the APOE e 4 allele risk factor for Alzheimer’s disease (AD) was recently found to have little short-term psychological risk. However, the impact of this knowledge on subjective ratings of memory and objective memory test performance of older adults is unknown. Methods:We administered objective verbal and visual memory tests, and self-rating scales of memory function, to 144 older adults (ages 52-89) with known APOE genotype who knew (e 4+: n 1⁄4 25; e 4-: n 1⁄4 49) or did not know (e 4+: n 1⁄4 25; e 4-: n 1⁄4 45) their genotype and genetic risk for AD prior to neuropsychological evaluation. Results: Although APOE genotype did not have an overall main effect on subjective self-ratings or objective memory scores, we observed significant genotype X disclosure interaction effects on several memory rating scales and tests of immediate and delayed verbal recall (all p’s<.05). Older adults who knew their e 4+ genotype tended to judge their memory more harshly and performed worse on an objective verbal memory test than did e 4+ adults who did not know. In contrast, older adults who knew their e 4genotype judged their memory more positively than did e 4adults who did not know, but these groups did not differ in objective memory test performance. The participant groups did not differ significantly in age, level of education, gender distribution, global ratings of depression (i.e., Geriatric Depression Scale) or global cognitive performance (i.e., Mini-Mental State Exam, Mattis Dementia Rating Scale). Conclusions: These results indicate that informing older adults that they have an APOE genotype associated with increased risk of AD can have adverse consequences on their perception of their memory abilities and their performance on objective memory tests. Therefore, clinicians and researchers should consider knowledge of genotype when evaluating older adults who may or may not be at risk for developing dementia. Similar implications can be drawn for those individuals who have knowledge of AD related risk based on neuroimaging or cerebrospinal fluid biomarkers.

Self Administered Gerocognitive Examination (SAGE) score changes over time in worried well, Mild Cognitive Impairment (MCI), dementia converter, and Alzheimer patients

decline is a hallmark of Alzheimer’s disease (AD), describing both risks and benefits in terms of changes in function is a logical choice for such an exercise and requires understanding the temporal relationship of changes in cognition and function. The objective of this study was to co-vary the individual items with Disability Assessment in Dementia (DAD) with measures of cognition and time to identify the temporal order associated with disease progression. Methods: 337 subjects (196 AD, 70 mild cognitive impairment, 71 cognitively healthy volunteers) were enrolled at 40 study sites across the US and Europe during 2006 and 2007 for an 18-month non-interventional study (ELN-AIP-901), sponsored by Elan Pharmaceuticals and Wyeth Research. Recruitment criteria were similar to those used in the ADNI study. DAD was performed at baseline and at 6-months intervals. DAD item scale scores were co-varied with Mini-Mental State Examination (MMSE) score using survival analysis. Results: Using median MMSE survival, patients were unable to perform activities for all items of the sub-domains for finance, medication, and outings at higher scores than for items in other sub-domains. The specific activities ‘‘organize finance’’ and ‘‘adequately organize correspondence’’ exhibited the shortest MMSE survival, ie, ‘‘lost’’ earlier in the course of the disease. The inability to perform items in the sub-domains of personal hygiene, dressing, eating, and continence occurred at lowest MMSE survivals, ie, ‘‘lost’’ at the later stages of AD progression. Seven items ‘‘lost’’ late in the course of the disease, lowest median MMSE survival, were from 3 of the 10 sub-domains, specifically dressing (4 items), eating (2 items), and continence (1 item). Conclusions: Inability to perform instrumental functional activities occurred earlier in the course of the disease, as measured by MMSE score, than basic functional activities. DAD items exhibit a hierarchical loss progression associated with cognitive decline, by MMSE. These findings support the use of DAD items that correlate with AD progression as a method for characterizing benefit and risk.