Effectiveness of procedural memory stimulation in mild Alzheimer's disease patients: A controlled study

This study concerns the effectiveness of procedural memory training in mild and mild-moderate probable Alzheimer's disease (AD) patients. Eleven patients with AD (age: 78 - 8.4 years; MMSE score: 20 - 3.4; education: 5.7 - 2.7 years) attending a day hospital, were individually trained, for three consecutive weeks (one hour/day; five days/week), in 13 basic and instrumental activities of daily living such as personal hygiene, using the telephone, dressing, reading, writing, etc. Seven AD patients (age: 74 - 12 years; MMSE score: 19 - 4.2; education: 5.3 - 3.2 years) constituted the control group. Patients in both groups underwent baseline and follow up assessment (four months later) recording the total mean time employed to perform the 13 activities of daily living. The training group showed a significant reduction (p < .025) in the time necessary to perform the activities, while the control group showed a non-significant increase. Our results support the view that procedural memory in mild and mild-moderate AD is relatively well preserved and that training of activities of daily living constitutes a realistic goal for rehabilitation programmes.     

Comparing two programs of cognitive training in Alzheimer's disease: a pilot study

OBJECTIVES: To evaluate the efficacy of two different procedures of individual cognitive training in mild to moderate Alzheimer's Disease (AD). MATERIAL AND METHODS: Twenty-two AD patients entered the study. We compared stimulation of procedural memory (group 1) with training of partially spared cognitive functions (group 2). Assessment included: neuropsychological tests, scales, and the Functional Living Skills Assessment (FLSA), a standardized battery built to directly evaluate patients' performance in everyday life. RESULTS: We observed a significant improvement for both groups after training in FLSA total score (P=0.005) and subscales. For group 1, we also found a slightly improved performance in two tests: Attentional Matrices (P=0.041), and Verbal Fluency for Letters (P=0.059). After 3 months, patients' results showed a tendency to regress to the pre-training level. CONCLUSION: Both AD groups showed a substantial improvement after training in a direct performance measure of everyday functioning. However, results at neuropsychological tests suggest that training activities of daily living (supported by procedural memory) may be more effective than stimulating "residual" cognitive functions.     

A study of the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) in an Icelandic elderly population

The Alzheimer's Disease Assessment Scale (ADAS) is designed for screening of cognitive and non-cognitive dysfunctions characteristic of persons with probable Alzheimer's disease (AD). The cognitive part of the scale (ADAS-Cog) is both convenient for screening of probable AD and as a measure of cognitive functioning during drug intervention. The aim of this study was to translate the ADAS-Cognitive sub-test (ADAS-Cog) into Icelandic and to study its application in an elderly Icelandic population. The Mini-Mental State Examination (MMSE) and the ADAS-Cog were administered to 20 AD patients and 20 controls. Each patient was also rated on the Global Deterioration Scale (GDS). The probable AD patients were divided into two groups based on their GDS: 3-4 and 5-6 points. The patients were also divided into two groups based on their MMSE score: very mild to mild (23-30 points) and mild to moderate (15-22 points). Furthermore, the subjects were divided into two age groups: 65-76 and 77-92 years. Results revealed a highly significant difference on MMSE (22.3 +/- 3.4; 26.8 +/- 1.6; P < 0.05) and ADAS-Cog (18.4 +/- 7.7; 7.3 +/- 3.5; P < 0.05) scores for patients and controls respectively. AD patients also performed significantly worse than the elderly control group on eight of the 11 sub-tests. Thus, the present findings are mainly in line with those of previous studies. The scale exceeds other screening tests such as the MMSE in that it addresses in more detail the symptoms of AD and is valuable for early detection of the illness and staging. ADAS-Cog plays an important role in the diagnostic makeup of AD along with other detailed investigations, such as neuropsychological assessment.     

Awareness of disease in dementia: preliminary results in patients with mild and moderate Alzheimer's disease

OBJECTIVE: To evaluate the presence and the level of awareness of disease in mild and moderate Alzheimer's disease (AD). METHOD: Cross-sectional evaluation of patients with mild/moderate AD (n=42) assessed by Assessment of Psychosocial Impact of the Dementia Diagnosis (APSID), Mini-mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDR). RESULTS: Awareness of disease and its consequences were present in 66.7% patients with mild AD (n=18). In moderate AD (n=24), 20.8% presented total awareness, 45.8% presented only awareness of cognitive symptoms. Unawareness of disease was observed in 33.3%. CONCLUSIONS: The present data show association between awareness and level of severity of disease. CDR 1 patients show a better recognition of cognitive and daily life activity symptoms, whereas CDR 2 patients recognized their cognitive symptoms but failed to appraise their severity and consequences in daily life activities.     

Errorless learning and spaced retrieval techniques to relearn instrumental activities of daily living in mild Alzheimer’s disease: A case report study

Previous studies on cognitive training in Alzheimer’s disease (AD) were principally aimed at making patients learn items not related to functional needs. However, AD patients also experience difficulties with instrumental activities of daily living (IADL). The goal of the present multiple baseline case report study was to assess the preliminary efficacy and tolerability of an individualized cognitive training program using the errorless learning (EL) and spaced-retrieval (SR) techniques to relearn forgotten IADLs in mild AD. Following an exhaustive neuropsychological assessment, two participants received two training sessions per week during four weeks. Participant A was trained to use his voice mail and Participant B, to manage the messages from his answering machine. The results showed that the program was well tolerated and improved performance on the trained tasks. These ameliorations were maintained over a 5-week period. The effects of the training did not have any impact on global cognitive functions since the results on these measures remained relatively stable. This case report demonstrated preliminary efficacy of a new cognitive training program using EL and SR techniques tailored to the needs of AD patients. This is an important finding since the loss of these capacities alters autonomy in AD patients.     

“Keep up the good work!”: A case study of the effects of a specific cognitive training in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by significant impairment in multiple cognitive domains. In recent years, the development of cognitive trainings in AD has received significant attention. In the present case study we designed a cognitive training program (GEO, Geographical Exercises for cognitive Optimization) based on an errorless paradigm and tailored to the patient’s cultural interests. The aim of this training was to investigate the potential for acquiring and possibly retaining both procedural and verbal knowledge in early-stage AD. This study involved an 80-year-old female patient diagnosed with early-stage AD, and 10 matched healthy subjects. Participants were asked to perform the two GEO training tasks: a “puzzle-like” task for procedural memory, and an “association” task for verbal memory. Both the patient and the healthy controls were subsequently trained with GEO using the same two tasks for 2 months. Although the patient’s performance before training in both tasks was poor compared to healthy controls, after the training these differences disappeared. Our results showed that the patient was able to acquire new procedural abilities and verbal knowledge, and that her achievements were stable at the follow-up testing scheduled 3 months after the end of the intervention. This case study suggests a potentially useful strategy for cognitive training in AD.     

Annualized functional change in Alzheimer's disease participants and normal controls

The rate of functional change in persons with mild Alzheimer's disease (AD) was compared to that of cognitively normal elderly control subjects. A comparison of annualized rates of change on the Test of Everyday Functional Abilities (TEFA) was carried out, along with a brief measure of instrumental activities of daily living skills, in persons with mild AD (Mini-Mental State Exam score >20) and cognitively normal elderly controls. Persons with AD (N = 30) showed an 8.5 % (3.5 point) annualized decline in TEFA scores over an average of 1.2 years; there was no decline in a group of elderly normal controls (N = 20) over an average of 1.5 years. Persons with mild AD showed functional changes over the course of a year on a direct measure of instrumental activities of daily living; a comparable group of normally aging persons did not.     

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial

BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD). OBJECTIVE: To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: Two hundred four patients with AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more. MAIN OUTCOME MEASURES: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of omega-3 fatty acid supplementation; and blood pressure determinations. RESULTS: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n = 32) with very mild cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was safe and well tolerated. CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE >27 points).     

Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial

BACKGROUND: The amyloid-beta peptide Abeta(42) has been implicated in the pathogenesis of Alzheimer's disease (AD). We aimed to test the effects of tarenflurbil, a selective Abeta(42)-lowering agent (SALA), on cognition and function in patients with mild to moderate AD. METHODS: 210 patients living in the community who had a mini-mental state examination (MMSE) score of 15-26 were randomly assigned to receive tarenflurbil twice per day (400 mg [n=69] or 800 mg [n=70]) or placebo (n=71) for 12 months in a phase II, multicentre, double-blind study. Primary efficacy outcomes were the AD assessment scale cognitive subscale (ADAS-cog), the Alzheimer's Disease Cooperative Study activities of daily living scale (ADCS-ADL), and the clinical dementia rating sum of boxes (CDR-sb). In a 12-month extended treatment phase, patients who had received tarenflurbil continued to receive the same dose, and patients who had received placebo were randomly assigned to tarenflurbil at 800 mg or 400 mg twice per day. Primary efficacy analyses were done by intention to treat. This trial is registered with Health Canada (084527) and the Medicines and Healthcare products Regulatory Agency in the UK (20365/0001/A 69316). FINDINGS: A prespecified interaction analysis revealed that patients with mild AD (baseline MMSE 20-26) and moderate AD (baseline MMSE 15-19) responded differently to tarenflurbil in the ADAS-cog and the ADCS-ADL (p>or=0.10); therefore, these groups were analysed separately. Patients with mild AD in the 800 mg tarenflurbil group had lower rates of decline than did those in the placebo group in activities of daily living (ADCS-ADL difference in slope 3.98 [95% CI 0.33 to 7.62] points per year, effect size [reduction from placebo decline rate] 46.4%, Cohen's d 0.45; p=0.033) and global function (CDR-sb difference -0.80 [-1.57 to -0.03] points per year, effect size 35.7%, Cohen's d 0.42; p=0.042); slowing of cognitive decline did not differ significantly (ADAS-cog difference -1.36 [-4.07 to 1.36] points per year, effect size 33.7%, Cohen's d 0.20; p=0.327). In patients with moderate AD, 800 mg tarenflurbil twice per day had no significant effects on ADCS-ADL and ADAS-cog and had a negative effect on CDR-sb (-52%, Cohen's d -1.08; p=0.003). The most common adverse events were diarrhoea (in seven, nine, and five patients in the 800 mg, 400 mg, and placebo groups, respectively), nausea (in seven, seven, and four patients), and dizziness (in five, nine, and four patients). Patients with mild AD who were in the 800 mg tarenflurbil group for 24 months had lower rates of decline for all three primary outcomes than did patients who were in the placebo group for months 0-12 and a tarenflurbil group for months 12-24 (all p<0.001), and had better outcomes than did patients who were in the placebo group for months 0-12 and the 800 mg tarenflurbil group for months 12-24 (all p<0.05). INTERPRETATION: 800 mg tarenflurbil twice per day was well tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild AD. FUNDING: Myriad Pharmaceuticals.     

Metrifonate therapy in Alzheimer's disease: a pooled analysis of four randomized, double-blind, placebo-controlled trials

This retrospective analysis assessed the efficacy of metrifonate in the treatment of mild to moderate Alzheimer's disease (AD). Those four studies meeting Food and Drug Administration guidelines for establishing the efficacy of an AD therapeutic agent were pooled for further analysis. Data were included from all patients valid for the intent-to-treat analyses (last observation carried forward). Patients received once daily placebo (n = 550), metrifonate 30-60 mg (by weight, n = 769) or 60/80 mg (by weight, n = 197). Metrifonate 60/80 mg significantly improved the cognitive abilities [AD Assessment Scale - Cognitive Subscale (ADAS-Cog), p = 0.0001; Mini Mental State Examination (MMSE), p = 0.0001], psychiatric and behavioral disturbances (Neuropsychiatric Inventory, p = 0.039; ADAS - Noncognitive Subscale, p = 0.0001), performance of instrumental and basic activities of daily living (Disability Assessment for Dementia, p = 0.0002) and global status (Clinician's Interview-Based Impression of Change with Caregiver Input, p = 0.0001) of AD patients when compared with placebo. Metrifonate effects across these domains were dose related. Metrifonate 60/80 mg significantly improved the cognitive performance relative to both placebo and to baseline as evaluated by both the ADAS-Cog and the MMSE. Metrifonate is the first cholinesterase inhibitor consistently shown under prospective, placebo-controlled conditions to improve significantly behavior in addition to cognition, function in activities of daily living and global functional status of patients with mild to moderate AD.     

Dissociative semantic breakdown in Alzheimer's disease: Evidence from multiple category fluency test

Background

Category-specific semantic dissociation particularly in terms of biological and non-biological dichotomy has been described in Alzheimer's disease (AD). We re-examine above finding by performing multiple superordinate category verbal fluency test in AD patients.

Method

We analyze the baseline neuropsychological assessment performance of food and animal fluency test of AD patients from a tertiary hospital that collected prospectively over 5 years period and correlation was calculated by Kappa test. The analysis is stratified according to literacy level (primary: 0–6 years education and secondary: >6 years education) and disease severity (MMSE score: mild 19-24, moderate 13-18 and severe <13).

Result

A total of 296 AD patients were analyzed and only fair to moderate agreement between food and animal category fluency test was found especially in the mild AD cases (primary: kappa 0.42; secondary: kappa 0.40). Kappa agreement level increases when disease progress especially in the secondary education group. Food category, which is a more relevant semantic knowledge to Singapore population, is generally more affected. Higher educated subjects appeared to have less semantic dissociation effect when disease progress.

Conclusion

Despite less primed in daily life, biological category of semantic knowledge appears to be affected less during AD process in highly urbanized Singapore society. Brain appears to have special protective mechanism towards living things. However, education level seems have a modulation effect towards the biological protective mechanism.     

Annualized functional change in alzheimer's disease participants and normal controls

The rate of functional change in persons with mild Alzheimer's disease (AD) was compared to that of cognitively normal elderly control subjects. A comparison of annualized rates of change on the Test of Everyday Functional Abilities (TEFA) was carried out, along with a brief measure of instrumental activities of daily living skills, in persons with mild AD (Mini-Mental State Exam score >20) and cognitively normal elderly controls. Persons with AD (N = 30) showed an 8.5 %?(3.5 point) annualized decline in TEFA scores over an average of 1.2 years; there was no decline in a group of elderly normal controls (N = 20) over an average of 1.5 years. Persons with mild AD showed functional changes over the course of a year on a direct measure of instrumental activities of daily living; a comparable group of normally aging persons did not.     

Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized,double‐blind,controlled trial investigating three dosages of Cerebrolysin

Background: Cerebrolysin is a neuropeptide preparation mimicking the effects of neurotrophic factors. This subgroup analysis assessed safety and efficacy of Cerebrolysin in patients with moderate to moderately severe Alzheimer’s disease (AD) (ITT data set: N = 133; MMSE: 14–20) included in a dose‐finding study (ITT data set: N = 251; MMSE: 14–25). Results of the mild AD subgroup (ITT data set: N = 118; MMSE: 21–25) are also presented. Methods: Patients with AD received 100 ml IV infusions of Cerebrolysin (10, 30 or 60 ml diluted in saline; N = 32, 34 and 35, respectively) or placebo (saline; N = 32) over twelve weeks (5 days per week for 4 weeks and 2 days per week for another 8 weeks). Primary efficacy criteria ADAS‐cog+ (Alzheimer’s Disease Assessment Scale Cognitive Subpart Modified) and CIBIC+ (Clinical Interview‐based Impression of Change with Caregiver Input) were assessed 24 weeks after baseline. Results: At week 24, Cerebrolysin improved the global clinical function significantly with all three dosages and induced significant improvements in cognition, initiation of activities of daily living (ADL) and neuropsychiatric symptoms at 10‐, 30‐ and 60‐ml doses, respectively. Treatment effects on total ADL and other secondary parameters (MMSE, Trail‐making test) were not significant. Cerebrolysin was safe and well tolerated. Conclusions: These results demonstrate the efficacy of Cerebrolysin in moderate to moderately severe AD, showing dose‐specific effects similar to those reported for patients with mild to moderate AD. The benefits of Cerebrolysin in advanced AD need to be confirmed in larger trials.     

Effects of AZD3480 on cognition in patients with mild-to-moderate Alzheimer's disease: a phase IIb dose-finding study

AZD3480 is a selective agonist of the central α4β2 and α2β2 neuronal nicotinic cholinergic receptors (NNRs). Its effects on cognition were investigated in 567 patients with mild-to-moderate Alzheimer's disease (AD) (Mini Mental State Examination [MMSE] 12-26). Mean baseline MMSE was 21 (SD ± 3.7), with 61% of patients having mild disease (MMSE 21-26). Mean age was 74 (range 58-85) years. Patients were randomized to one of 5 treatment groups: AZD3480 5 mg, 20 mg or 35/100 mg, donepezil 10 mg (active comparator) or placebo, and treated once daily for 12 weeks. The primary outcome measure was change from baseline at Week 12 on the AD Assessment Scale-Cognitive Subscale (ADAS-Cog). Neither AZD3480 nor donepezil showed a statistically significant improvement versus placebo on ADAS-Cog. Improvements in a number of secondary outcome measures (MMSE, AD Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and Disability Assessment for Dementia [DAD]) were observed for AZD3480 and for donepezil. A post-hoc analysis on ADAS-Cog, excluding patients with very mild AD (MMSE 25-26) indicated improvement versus placebo for AZD3480 20 mg (-1.4, 95% CI: -3.0; 0.2) and donepezil (-1.0, 95% CI: -2.3; 0.3). AZD3480 was well tolerated. The study did not meet proof of concept criteria: since neither AZD3480 nor donepezil were statistically significantly superior to placebo on ADAS-Cog and was considered to be inconclusive. Further studies are required to determine the therapeutic potential of stimulating α4β2 receptors with NNRs in AD patients.     

Patients with Lewy body dementia use more resources than those with Alzheimer's disease

OBJECTIVES: The purpose of this study was to compare resource use and costs in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) and to assess determinants of costs of care in DLB. METHOD: Thirty-four patients with DLB were included in a cross-sectional study. The patients were matched with respect to age, gender and Mini Mental State Examination (MMSE) score to 34 patients with AD. Both groups were examined using Resource Utilisation in Dementia (RUD Lite), MMSE and the Neuropsychiatric inventory (NPI). The DLB patients were additionally examined using the Disability Assessment for Dementia Scale (DAD). RESULTS: Costs of care in patients suffering from DLB was on average 348,000 SEK (37,500 euro) per year compared to 169,000 SEK (18,200 euro) in the AD group (p < 0.001). Within the DLB group, care costs correlated significantly (r(c) = 2.77, p < 0.001) with dependency in instrumental activities of daily living measured with DAD, whereas MMSE and NPI were not significantly correlated to resource use in the DLB group. CONCLUSIONS: DLB patients use more resources, and are more costly than AD patients. Dependency in instrumental activities of daily living is strongly correlated to resource use in DLB patients.     

Is functional decline necessary for a diagnosis of Alzheimer's disease?

BACKGROUND: The purpose of this study is to examine baseline differences and annualized cognitive and functional change scores in mild Alzheimer's disease (AD) patients with and without impaired activities of daily living (ADL). METHODS: We recruited 267 mild probable AD patients with at least 1 year of follow-up (NINCDS-ADRDA criteria, MMSE>or=20). Based on initial ADL scores, they were divided into 2 groups: unimpaired (n=40) and impaired (n=227). We compared the differences in annualized change scores on MMSE, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), ADL and Clinical Dementia Rating sum of box score (CDR-SB) for patients with and without functional impairment at baseline. RESULTS: The group with unimpaired ADL at baseline had a significantly shorter symptom duration (p=0.01) and better neuropsychological test scores at baseline (p<0.001) than those with impaired ADL. The annualized cognitive and functional change of each group from baseline to 1-year follow-up was not significantly different on the MMSE, ADAS-cog, CDR-SB, Physical Self-Maintenance Scale and Instrumental Activities of Daily Living. After 1 year, 56% of the initially unimpaired group and 6% of the initially impaired group reported no ADL impairment. CONCLUSIONS: Our study suggests that functional decline should not be required for the diagnosis of mild AD.     

天智颗粒治疗轻、中度阿尔茨海默病临床研究

目的评价天智颗粒治疗轻、中度阿尔茨海默病(alzheimer disease,AD)的有效性及安全性。方法选择简易智能状态量表(MMSE)轻、中度AD患者60例,随机分成治疗组和对照组各30例,治疗组给予天智颗粒联合吡拉西坦治疗,对照组给予吡拉西坦治疗,观察12周。治疗前后应用简易智能状态量表MMSE,日常生活能力量表(ADL)评价临床疗效;用不良反应量表(TESS)评定不良反应。结果观察12周,天智颗粒治疗组较对照组MMES、ADL评分明显改善(P<0.01)。治疗组天智颗粒治疗12周后较治疗前MMSE与ADL分数分别改善3.8分和8.0分(P<0.05,P<0.01)。天智颗粒治疗组不良反应轻,与吡拉西坦对照组比较2组差异无显著意义(P>0.05)。结论天智颗粒能有效治疗轻、中度AD患者,对患者的认知功能和日常生活自理能力均有改善,耐受性好,安全性高。     

Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients.

BACKGROUND: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period. METHODS: Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2+/-7.2; mean Mini-Mental State Examination score, MMSE: 19.8+/-3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11+/-2.6 months of chronic Donepezil administration (5mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4+/-5.7, MMSE score: 20.6+/-3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13+/-1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings. RESULTS: The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6+/-3.5 to 17.8+/-4.4) and in treated (from 19.8+/-3.5 to 17.8+/-4.1) group. At t(0), the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region. CONCLUSIONS: Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.     

The Atorvastatin/Donepezil in Alzheimer’s Disease Study (LEADe): Design and baseline characteristics

BackgroundGrowing evidence suggests that elevated cholesterol levels in mid-life are associated with increased risk of developing Alzheimer’s disease (AD), and that statins might have a protective effect against AD and dementia. The Lipitor’s Effect in Alzheimer’s Dementia (LEADe) study tests the hypothesis that a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild to moderate AD in patients receiving background therapy of a cholinesterase inhibitor (donepezil 10 mg daily).MethodsThis is an international, multicenter, double-blind, randomized, parallel-group study with a double-blind randomized withdrawal phase of patients with mild to moderate AD (Mini-Mental State Examination [MMSE] score, 13 to 25). Inclusion criteria included age 50 to 90 years, receiving donepezil 10 mg for at least 3 months before randomization, and low-density lipoprotein cholesterol levels (LDL-C) 2.5 to 3.5 mmol/L (95 to 195 mg/dL). Co-primary end points are changes in AD Assessment Scale-cognitive subscale (ADAS-cog) and AD Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale scores. A confirmatory end point is rate of change in whole brain and hippocampal volumes in patients who enrolled in the magnetic resonance imaging substudy.ResultsEnrollment of 641 subjects is complete. The baseline mean data are age 74 ± 8 years, 53% women, MMSE 22 ± 3, ADAS-cog 23 ± 10, AD Functional Assessment and Change Scale (ADFACS) 13 ± 9, Neuropsychiatric Inventory (NPI) 10 ± 11, and Clinical Dementia Rating-Sum of Boxes (CDR-SB) 6 ± 3. Mean prior donepezil treatment was 409 ± 407 days. Mean baseline lipid levels are total cholesterol 5.8 ± 0.8 mmol/L (224 ± 33 mg/dL), LDL-C 3.7 ± 0.7 mmol/L (143 ± 26 mg/dL), triglycerides 1.5 ± 0.7 mmol/L (132 ± 64 mg/dL), and high-density lipoprotein cholesterol 1.6 ± 0.5 mmol/L (64 ± 18 mg/dL).ConclusionsLEADe will report in 2008 and is expected to provide a more definitive evaluation of the potential for statins in the treatment of people with AD.     

Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease

BACKGROUND: Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. OBJECTIVE: To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. DESIGN: Cross-sectional cohort design. Patients/ METHODS: We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. RESULTS: We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. CONCLUSION: There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future.