Alzheimers Abstracts 16

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High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.
            (Aisen et al., 2008)  Download
CONTEXT:  Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. OBJECTIVE:  To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. DESIGN, SETTING, AND PATIENTS:  A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. INTERVENTION:  Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months. MAIN OUTCOME MEASURE:  Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). RESULTS:  A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements. CONCLUSION:  This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. TRIAL REGISTRATION:  clinicaltrials.gov Identifier: NCT00056225.


 

Effects of acetyl-L-carnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors.
            (Bianchetti et al., 2003)  Download
Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.

Acetyl-carnitine and Alzheimer's disease.
            (Bowman, 1992)  Download
In a double-blind, randomized, controlled clinical trial, progression of Alzheimer’s disease was significantly reduced in patients who received acetyl-carnitine (2 g/day) for one year.

Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach.
            (Brooks et al., 1998)  Download
OBJECTIVES:  To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. DESIGN:  Longitudinal, double-blind, parallel-group, placebo-controlled. SETTING:  Twenty-four outpatient sites across the United States. PARTICIPANTS:  A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). MEASUREMENTS:  Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. RESULTS:  The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age. CONCLUSIONS:  ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.


 

Action of acetyl-L-carnitine in neurodegeneration and Alzheimer's disease.
            (Calvani et al., 1992)  Download
ALC has to be considered a nemoprotective agent, able to stimulate and restorz the metabolic machinery of surviving neurons. Its benefit in patients is that it slows the course of primary degenerative dementia, actually improving some cognitive and behavioral areas. The potential use of ALC in a number of progressive neurodegenerative disorders should be investigated carefully.

A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease.
            (Connelly et al., 2008)  Download
OBJECTIVES:  (1) to assess the effect of 1 mg folic acid supplementation of cholinesterase inhibitors (ChI) in a 6 month double-blind placebo-controlled study of patients with Alzheimer's Disease (AD) and (2) to assess whether outcome measures were affected by changes in homocysteine levels. METHOD:  Fifty-seven consecutive outpatients with probable AD were treated concurrently with a ChI and either folic acid or placebo. None had conditions or medication known to interfere with folate metabolism. Fasting folate and homocysteine levels were measured prior to commencing ChI and 6 months later. Response was categorised using criteria of the National Institute of Clinical Excellence (NICE). RESULTS:  Twelve males and 29 females completed treatment (mean age 76.27 SD 6.23 years, Mini-Mental State Examination (MMSE) 23.49 SD 3.53, baseline homocysteine 18.39 SD 4.62 micromoles per litre). 23 received folic acid and 18 placebo. There were no significant baseline differences or use of individual ChI between the two arms. After 6 months a significant difference was seen in the change from baseline in combined Instrumental Activities of Daily Living and Social Behaviour scores between arms (folate+1.50 (SD 5.32) vs placebo -2.29 (SD 6.16) (p=0.03) but not change in MMSE scores. Sixteen of 23 subjects receiving folic acid and 7/18 placebo subjects were classified as NICE responders (p=0.05). CONCLUSION:  This pilot double blind study suggests that response to ChI in patients with AD may be improved by the use of folic acid. The relationship between any change in homocysteine levels and response to treatment is discussed.

Ginkgo biloba for prevention of dementia: a randomized controlled trial.
            (DeKosky et al., 2008)  Download
CONTEXT:  Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G. biloba on dementia incidence are lacking. OBJECTIVE:  To determine effectiveness of G. biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS:  Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n = 2587) or MCI (n = 482) at study entry were assessed every 6 months for incident dementia. INTERVENTION:  Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or placebo (n = 1524). MAIN OUTCOME MEASURES:  Incident dementia and AD determined by expert panel consensus. RESULTS:  Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G. biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G. biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G. biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94-1.33; P = .21) and for AD, 1.16 (95% CI, 0.97-1.39; P = .11). G. biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85-1.50; P = .39). CONCLUSIONS:  In this study, G. biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. Trial Registration clinicaltrials.gov Identifier: NCT00010803.

Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's disease.
            (Exley et al., 2006)  Download
There are unexplained links between human exposure to aluminium and the incidence, progression and aetiology of Alzheimer's disease. The null hypothesis which underlies any link is that there would be no Alzheimer's disease in the effective absence of a body burden of aluminium. To test this the latter would have to be reduced to and retained at a level that was commensurate with an Alzheimer's disease-free population. In the absence of recent human interference in the biogeochemical cycle of aluminium the reaction of silicic acid with aluminium has acted as a geochemical control of the biological availability of aluminium. This same mechanism might now be applied to both the removal of aluminium from the body and the reduced entry of aluminium into the body while ensuring that essential metals, such as iron, are unaffected. Based upon the premise that urinary aluminium is the best non-invasive estimate of body burden of aluminium patients with Alzheimer's disease were asked to drink 1.5 L of a silicic acid-rich mineral water each day for five days and, by comparison of their urinary excretion of aluminium pre-and post this simple procedure, the influence upon their body burden of aluminium was determined. Drinking the mineral water increased significantly (P<0.001) their urinary excretion of silicic acid (34.3 +/- 15.2 to 55.7 +/- 14.2 micromol/mmol creatinine) and concomitantly reduced significantly P=0.037) their urinary excretion of aluminium (86.0 +/- 24.3 to 62.2 +/- 23.2 nmol/mmol creatinine). The latter was achieved without any significant (P>0.05) influence upon the urinary excretion of iron (20.7 +/- 9.5 to 21.7 +/- 13.8 nmol/mmol creatinine). The reduction in urinary aluminium supported the future longer-term use of silicic acid as non-invasive therapy for reducing the body burden of aluminium in Alzheimer's disease.


 

Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E.
            (Fillenbaum et al., 2005)  Download
BACKGROUND:  Since increased oxidative stress may impair cognition and be a risk factor for dementia, there has been interest in determining whether use of antioxidants could protect against such events. OBJECTIVE:  To determine whether supplement use of vitamins C and/or E in a community-based sample of older African American and white individuals delayed incident dementia or Alzheimer's disease (AD). METHODS:  We selected a subgroup from the Duke Established Populations for Epidemiologic Studies of the Elderly, a longitudinal study of community-representative persons aged 65-105 years living in 5 adjacent counties in North Carolina, and followed them for dementia (1986-1987 through June 2000). Information gathered during in-home interviews included sociodemographic characteristics, health status, health service use, and vitamin use. Diagnosis of dementia and AD was based on evaluations using the clinical and neuropsychological batteries of the Consortium to Establish a Registry for Alzheimer's Disease, with final determination by consensus agreement of specialists using Diagnostic and Statistical Manual of Mental Disorders, third revision, and National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. RESULTS:  Of 616 persons initially dementia-free (mean age 73 y; 62% female; 62% African American), 141 developed dementia, of whom 93 developed AD. Increased age and mobility problems were risk factors for dementia (only age for AD), while an increased number of outpatient visits reduced the likelihood of developing dementia. Neither use of any vitamins C and/or E (used by 8% of subjects at baseline) nor high-dose use reduced the time to dementia or AD. CONCLUSIONS:  In this community in the southeastern US where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or AD.

An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease.
            (Heo et al., 2008)  Download
BACKGROUND AND PURPOSE:  Ginseng is one of the most popular herbs worldwide. Ginseng has various medical applications, and it seems to have significant effects as a cognition-enhancing drug. In this study, we examined the efficacy of Korean red ginseng (KRG) as an adjuvant therapy to conventional anti-dementia medications in patients with Alzheimer's disease. METHODS:  The trial was designed as a 12-week randomized study. Sixty-one patients (24 males and 37 females) with Alzheimer's disease were randomly assigned to one of the following treatment groups: low-dose KRG (4.5 g/day, n = 15), high-dose KRG (9 g/day, n = 15) or control (n = 31). The Alzheimer's Disease Assessment Scale (ADAS), Korean version of the Mini-Mental Status Examination (K-MMSE) and Clinical Dementia Rating (CDR) scale were used to assess the change in cognitive and functional performance at the end of the 12-week study period. RESULTS:  The patients in the high-dose KRG group showed significant improvement on the ADAS and CDR after 12 weeks of KRG therapy when compared with those in the control group (P = 0.032 and 0.006 respectively). The KRG treatment groups showed improvement from baseline MMSE when compared with the control group (1.42 vs. -0.48), but this improvement was not statistically significant. CONCLUSIONS:  KRG showed good efficacy for the treatment of Alzheimer's disease; however, further studies with larger samples of patients and a longer efficacy trial should be conducted to confirm the efficacy of KRG.

Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial.
            (Kanowski and Hoerr, 2003)  Download
In 1996, Kanowski et al. reported about the beneficial effects of ginkgo biloba special extract EGb 761 (240 mg/day) in outpatients with pre-senile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) of mild to moderate severity. The comparison of the results of this double-blind, placebo-controlled, randomized, multi-center study with other dementia studies is hampered by the fact that only the responder analysis of the per-protocol (PP) population, which was pre-specified in the protocol as confirmatory analysis, has been published in detail so far. Moreover, cognitive functioning was measured using the Syndrom-Kurztest (SKT), whereas results of other studies are based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Therefore, the conventional intention-to-treat (ITT) analysis of this study is provided with an estimation of ADAS-cog scores based on measured SKT scores. After 24 weeks of treatment, the ITT analysis of the SKT and estimated ADAS-cog scores revealed a mean decrease in the total score by -2.1 (95 % CI: -2.7; -1.5) points and -2.7 (95 % CI: -3.5; -1.9) points, respectively, for the EGb 761 group, which indicates an improvement in cognitive function. On the contrary, the placebo group exhibited only a minimal change of -1.0 (95 % CI: -1.6; -0.3) and -1.3 (95 % CI: -2.0; -0.4) points, respectively. The changes from baseline differed significantly between treatment groups by 1.1 (SKT) and 1.4 (estimated ADAS-cog) points, respectively (P = 0.01). The Clinical Global Impression of Change (CGI, Item 2) favored the EGb 761 group with a mean difference of 0.4 points (P = 0.007). Changes in the rating related to activities of daily living (Nürnberger-Alters-Beobachtungs-Skala, NAB) showed a favorable trend for EGb 761R. A subgroup analysis regarding patients with DAT yielded comparable results. Using a decrease of at least 4 points on the estimated ADAS-cog scores as cutoff criterion for treatment response, 35 % of EGb 761-treated patients were considered responders versus only 19 % for the placebo group (P = 0.01). The results of this ITT analysis substantiate the outcomes previously obtained with a responder analysis of the per-protocol population and confirm that EGb 761 improves cognitive function in a clinically relevant manner in patients suffering from dementia. The therapeutic effect is in line with the outcome of another EGb 761 study conducted in the U.S.


 

Combination therapy of donepezil and vitamin E in Alzheimer disease.
            (Klatte et al., 2003)  Download
A retrospective chart review was performed on 130 patients from the Ohio State University Memory Disorders Clinic to examine the long-term effects of combination therapy with donepezil and vitamin E on patients with Alzheimer disease. Subjects were included if they met National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease, had taken at least 5 mg donepezil and at least 1000 U vitamin E daily, had at least a 1-year follow-up while continuing these medications, and had a Mini-Mental State Examination score of 10-24. The Mini-Mental State Examination was then recorded annually thereafter. These data were compared with the Consortium to Establish a Registry for Alzheimer's Disease database for patients collected prior to the availability of these treatment options. Patients declined at a significantly lower rate as compared with the Consortium to Establish a Registry for Alzheimer's Disease data. The long-term combination therapy of donepezil and vitamin E appears beneficial for patients with Alzheimer disease. Future prospective studies would be needed to compare combination treatment to vitamin E and donepezil alone.

Influence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimer's disease.
            (Le Bars et al., 2002)  Download
OBJECTIVE:  To explore the treatment effect of EGb 761((R)) (EGb) in Alzheimer's disease depending on baseline severity. METHODS:  We applied stratification to the intent-to-treat data set collected during a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with 120 mg of EGb, using cutoff points of 23 and 14 for the Mini-Mental State Examination (MMSE) score. Outcome measures used were the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) and the Geriatric Evaluation by Relative's Rating Instrument (GERRI). RESULTS:  In the severity stratum 1 (MMSE >23), the placebo group did not show significant changes, while the EGb group improved significantly by 1.7 points on the ADAS-Cog and by 0.09 points on the GERRI. In the severity stratum 2 (MMSE <24), the placebo group worsened by 4.1 points on the ADAS-Cog and 0.18 points on the GERRI, whereas the EGb group showed 60% less decline on the ADAS-Cog (treatment difference of 2.5 points) and no change on the GERRI (treatment difference of 0.25 points). The most severely impaired subgroup (MMSE <15) showed slightly more pronounced worsening for both treatment groups. However, in comparison to placebo, EGb induced virtually the same magnitude of effect as was observed in the entire stratum 2. CONCLUSIONS:  The results of this retrospective analysis indicated that a treatment effect favorable to EGb could be observed with respect to cognitive performance (p = 0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. However, the relative changes from baseline measured at endpoint depended heavily on the severity at baseline. Improvement was observed in the group of patients with very mild to mild cognitive impairment, while in more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo.


Panax ginseng enhances cognitive performance in Alzheimer disease.
            (Lee et al., 2008)  Download
Recent experimental evidences suggest protective and trophic effects of ginseng in the memory function of Alzheimer disease (AD). Thus, we investigated the clinical efficacy of Panax ginseng in the cognitive performance of AD patients in an open-label study. Consecutive AD patients were randomly assigned to the ginseng (n=58) or the control group (n=39), and the ginseng group was treated with Panax ginseng powder (4.5 g/d) for 12 weeks. Cognitive performances were monitored using the mini-mental state examination (MMSE) and Alzheimer disease assessment scale (ADAS) during 12 weeks of the ginseng treatment and at 12 weeks after the ginseng discontinuation. MMSE and ADAS scales showed no baseline difference between the groups. After ginseng treatment, the cognitive subscale of ADAS and the MMSE score began to show improvements and continued up to 12 weeks (P=0.029 and P=0.009 vs. baseline, respectively). After discontinuing ginseng, the improved ADAS and MMSE scores declined to the levels of the control group. These results suggest that Panax ginseng is clinically effective in the cognitive performance of AD patients.

Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
            (Meador et al., 1993) Download
Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies.

Thiamine therapy in Alzheimer's disease.
            (Mimori et al., 1996) Download
Fursultiamine (TTFD), a derivative of thiamine, at an oral dose of 100 mg/day had a mild beneficial effect in patients with Alzheimer's disease in a 12-week open trial. The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function. Only mildly impaired subjects showed cognitive improvement. Alzheimer patients' blood levels of thiamine before the trial were within the normal range. No adverse reactions were observed and all patients tolerated the trial well. TTFD could afford an alternate treatment to large doses of thiamine hydrochloride in Alzheimer patients. However, further investigations of the therapeutic implications of thiamine and its possible etiologic clues to Alzheimer's disease are necessary.


A trial of thiamine in Alzheimer's disease.
            (Nolan et al., 1991) Download
Because a previous short-term study demonstrated a statistically significant, but not clinically important, improvement in cognitive test scores during thiamine treatment in patients with dementia of the Alzheimer's type, a 12-month, double-blind, parallel-group study was conducted to examine whether long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type. Fifteen subjects were enrolled and 10 completed the 1-year study. Data are available for two additional subjects through the first 9 months of study. No significant differences were found between the placebo and thiamine groups at any point during the study. In both groups, overall means for the Mini-Mental State Examination, verbal learning, and naming scores decreased significantly over the 12-month study period. These results do not support the hypothesis that long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type.

 


References

Aisen, PS, et al. (2008), ‘High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial.’, JAMA, 300 (15), 1774-83. PubMed: 18854539
Bianchetti, A, R Rozzini, and M Trabucchi (2003), ‘Effects of acetyl-L-carnitine in Alzheimer’s disease patients unresponsive to acetylcholinesterase inhibitors.’, Curr Med Res Opin, 19 (4), 350-53. PubMed: 12841930
Bowman, BA (1992), ‘Acetyl-carnitine and Alzheimer’s disease.’, Nutr Rev, 50 (5), 142-44. PubMed: 1630720
Brooks, JO, et al. (1998), ‘Acetyl L-carnitine slows decline in younger patients with Alzheimer’s disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach.’, Int Psychogeriatr, 10 (2), 193-203. PubMed: 9677506
Calvani, M, et al. (1992), ‘Action of acetyl-L-carnitine in neurodegeneration and Alzheimer’s disease.’, Ann N Y Acad Sci, 663 483-86. PubMed: 1482095
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Exley, C, et al. (2006), ‘Non-invasive therapy to reduce the body burden of aluminium in Alzheimer’s disease.’, J Alzheimers Dis, 10 (1), 17-24; discussion 29. PubMed: 16988476
Fillenbaum, GG, et al. (2005), ‘Dementia and Alzheimer’s disease in community-dwelling elders taking vitamin C and/or vitamin E.’, Ann Pharmacother, 39 (12), 2009-14. PubMed: 16227448
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Kanowski, S and R Hoerr (2003), ‘Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial.’, Pharmacopsychiatry, 36 (6), 297-303. PubMed: 14663654
Klatte, ET, et al. (2003), ‘Combination therapy of donepezil and vitamin E in Alzheimer disease.’, Alzheimer Dis Assoc Disord, 17 (2), 113-16. PubMed: 12794389
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Lee, ST, et al. (2008), ‘Panax ginseng enhances cognitive performance in Alzheimer disease.’, Alzheimer Dis Assoc Disord, 22 (3), 222-26. PubMed: 18580589
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Mimori, Y, H Katsuoka, and S Nakamura (1996), ‘Thiamine therapy in Alzheimer’s disease.’, Metab Brain Dis, 11 (1), 89-94. PubMed: 8815393
Nolan, KA, et al. (1991), ‘A trial of thiamine in Alzheimer’s disease.’, Arch Neurol, 48 (1), 81-83. PubMed: 1986730