A Quick Test of cognitive speed is sensitive in detecting early treatment response in Alzheimer's disease

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, S-205 02 Malmö, Sweden. .
Alzheimer's Research and Therapy (Impact Factor: 3.98). 10/2010; 2(5):29. DOI: 10.1186/alzrt53
Source: PubMed


There is a great need for quick tests that identify treatment response in Alzheimer's disease (AD) to determine who benefits from the treatment. In this study, A Quick Test of cognitive speed (AQT) was compared with the mini-mental state examination (MMSE) in the evaluation of treatment outcome in AD.
75 patients with mild to moderate AD at a memory clinic were assessed with AQT and the MMSE at a pretreatment visit, at baseline and after 8 weeks of treatment with cholinesterase inhibitors (ChEI) initiated at baseline. Changes in the mean test scores before and after treatment were compared, as well as the number of treatment responders detected by each test, according to a reliable change index (RCI).
After 8 weeks of treatment, the AQT improvement, expressed as a percentage, was significantly greater than that of the MMSE (P = 0.026). According to the RCI, the cut-offs to define a responder were ≥16 seconds improvement on AQT and ≥3 points on the MMSE after 8 weeks. With these cut-offs, both tests falsely classified ≤5% as responders during the pretreatment period. After 8 weeks of treatment, AQT detected significantly more responders than the MMSE (34% compared with 17%; P = 0.024). After 6 months of treatment, the 8-week AQT responders still showed a significantly better treatment response than the AQT nonresponders (22.3 seconds in mean difference; P < 0.001).
AQT detects twice as many treatment responders as the MMSE. It seems that AQT can, already after 8 weeks, identify the AD patients who will continue to benefit from ChEI treatment.

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    • "In the present study of mild AD, which includes all three ChEI agents, the three-year decline in ADAS-cog was 6.12 points and MMSE 3.10 points, suggesting a similar rate of change as in our previously described mild-to-moderate SATS group [10,26]. The US Food and Drug Administration has defined an improvement of at least four points in the ADAS-cog score as clinically significant (reported in [27,28]), and a MMSE change of three points has been suggested to indicate a clinically significant alteration in cognitive ability [29,30]. From the Alzheimer’s Disease Neuroimaging Initiative, Schneider et al.[31] reported that the ChEI-treated participants with mild AD deteriorated, on average, 9.25 points in ADAS-cog and 4.19 points in MMSE scores after two years in the study. "
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    ABSTRACT: Knowledge of longitudinal progression in mild Alzheimer's disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in mild AD patients in a routine clinical setting. This was a prospective, open-label, non-randomized, multicenter study of ChEI treatment (donepezil, rivastigmine or galantamine) conducted during clinical practice. The 734 mild AD patients (Mini-Mental State Examination (MMSE) score 20 to 26) were assessed at baseline and then semi-annually over three years. Outcome measures included the MMSE, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinician's Interview-Based Impression of Change (CIBIC) and Instrumental Activities of Daily Living (IADL) scale. After three years of ChEI therapy, 31% (MMSE) and 33% (ADAS-cog) of the patients showed improved/unchanged cognitive ability, 33% showed improved/unchanged global performance and 14% showed improved/unchanged IADL capacity. Higher mean dose of ChEI and lower educational level were both predictors of more positive longitudinal cognitive and functional outcomes. Older participants and those with a better IADL score at baseline exhibited a slower rate of cognitive decline, whereas younger participants and those with higher cognitive status showed more preserved IADL ability over time. Gender and apolipoprotein E (APOE) genotype showed inconsistent results. Prediction models using the abovementioned scales are presented. In naturalistic mild AD patients, a marked deterioration in IADL compared with cognitive and global long-term outcomes was observed, indicating the importance of functional assessments during the early stages of the disease. The participants' time on ChEI treatment before inclusion in studies of new therapies might affect their rate of decline and thus the comparisons of changes in scores between various studies. An increased understanding of expected disease progression in different domains and potential predictors of disease progression is essential for assessment of future therapies in AD.
    Alzheimer's Research and Therapy 10/2013; 5(5):44. DOI:10.1186/alzrt210 · 3.98 Impact Factor
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    • "AD is a progressive neurodegenerative disease characterized by the loss of cholinergic neurons in the nucleus basalis of Meynert, which is the basement of the cholinergic hypothesis and results in the subsequent development of acetylcholinesterase (AChE) inhibitors in AD treatment 9. AChE inhibitors are used to treat the patients with mild to moderate AD 10. Since Donepezil can upregulate AChE activities significantly and increase the protein level of CSF in the patients with AD 11, it has been widely used in the symptomatic treatments of AD 12. "
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    ABSTRACT: To evaluate the efficacy and safety of donepezil plus natural hirudin in patients with mild-to-moderate Alzheimer's Disease. In the 20-week, randomized, open-label and controlled study, 84 patients received either donepezil (5 mg/day for the first 4 weeks and 10 mg/day thereafter) or donepezil plus natural hirudin (3 g/day) treatment. Efficacy was reflected by the change of the total scores of Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog), Activities of Daily Life (ADL) and Neuropsychiatric Inventory (NPI). The patients with the donepezil plus natural hirudin treatment showed more significant improvement in the daily activities and the decline of the cognition than those with donepezil treatment. Significant difference was present in the groups since the 8th week. No group difference was found in the NPI change. However, within the hirudin treatment group, more powerful efficacy including NPI assessment was found in the patients with vascular risk factors (VRF) as comparing to with those without VRF. The combination of donepezil and natural hirudin was well tolerated. The dropout rate was greater in the donepezil and natural hirudin (50%) treatment group than in the donepezil (39%) treatment group. Similar result was found in the incidence of adverse events (23.8% vs 19.0%), but there was no statistical difference between the two groups. Adverse events were the most common reason for the dropout. Although hemorrhage and hypersensitiveness were more common in donepezil plus Maixuekang treatment (11.9% and 7.1%) group than in donepezil treatment (2.4% and 2.4%) group, no significant difference was present between the two groups. Economic problem was another important reason for the patients' withdrawal. Compared with the donepezil treatment in the patients with mild-to-moderate AD, our results suggest that donepezil combined with natural hirudin may improve the treatment effects in the ADL, BPSD and cognition of the patients. Furthermore, this joint treatment is safe.
    International journal of medical sciences 05/2012; 9(3):248-55. DOI:10.7150/ijms.4363 · 2.00 Impact Factor
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    ABSTRACT: Objective: This retrospective study used A Quick Test of Cognitive Speed (AQT) to compare processing speed and efficiency measures by adults with attention-deficit/hyperactivity disorder (ADHD) or non-ADHD psychiatric disorders and healthy controls. Method: Color, form, and color-form combination naming tests were administered to 104 adults, ages 17-55 years, referred for psychiatric evaluation of possible ADHD. Thirty healthy adults were controls. Psychiatric intake procedures identified 64 adults with ADHD (ICD-10 and DSM-IV criteria) and 40 with mild psychiatric disorders without ADHD. The study was conducted from 2008 through 2010. Results: At intake, color, form, and color-form combination naming times (seconds) were longer and overhead [color-form combination - (color + form)] was larger for patients with ADHD than for non-ADHD patients and controls. In the ADHD group, color and form measures were in the normal range. Color-form combination was in the slower-than-normal speed (60-70 seconds) and overhead, a processing-efficiency measure, in the atypical range (> 10 seconds). In the non-ADHD patient and control groups, all AQT measures were in the normal range. Analysis of variance with post hoc analysis of log-normal values for color, form, and color-form combination and time for overhead indicated significant (Bonferroni P < .01) mean differences between the ADHD and other groups, but not between the non-ADHD and control groups. When using fail criteria for either color-form combination or overhead, the sensitivity for the ADHD group was 89%. Conclusions: RESULTS support AQT as a possible complement to psychiatric intake procedures to differentiate adults with ADHD from those with mild psychiatric disorders, and they suggest that a controlled prospective study might be productive.
    03/2012; 14(2). DOI:10.4088/PCC.11m01273
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