Dr. Ron’s Research Review – January 29, 2020

©

This week’s research review focuses on nutrition for Alzheimer’s disease.

A nutritional formulation improved the Dementia Rating Scale in patients with Alzheimer's disease in a phase II randomized clinical trial for cognition and mood. (Remington et al., 2015)
A study published in the Journal of Alzheimer's Disease determined whether nutritional intervention could positively impact cognitive performance and behavioral difficulties for individuals diagnosed with Alzheimer's disease (AD). The University of Massachusetts Lowell, Lowell, MA and  Framingham State University, Framingham, MA, conducted the study.
A double-blind, multi-site, phase II study was conducted in which 106 individuals with AD were randomized to a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open-label extension where participants received NF for 6 additional months.
The nutraceutical formulation cohort improved versus the placebo cohort within 3 months (Clox-1 p = 0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722, 2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric Inventory. Both cohorts improved or maintained baseline performance during open-label extensions. Activities of Daily Living did not change for either cohort.
These findings extend phase I studies where a nutraceutical formulation maintained or improved cognitive performance and mood/behavior. (Remington et al., 2015)

A vitamin/nutriceutical formulation was found beneficial for early-stage Alzheimer's disease in a 1-year, open-label pilot study with a 16-month caregiver extension. (Chan et al., 2008)
A study published in the American Journal of Alzheimer's Disease & Other Dementias examined the efficacy of a vitamin/nutriceutical formulation (folate, vitamin B6, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine) in early-stage Alzheimer's disease. The Center for Cell Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, MA, conducted the study.
A 12-month, open-label trial included 14 community-dwelling individuals with early-stage Alzheimer's disease.
Participants improved in the Dementia Rating Scale and Clock-drawing tests (Clox 1 and 2). Family caregivers reported improvement in multiple domains of the Neuropsychiatric Inventory (NPI) and maintenance of performance in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADL). Sustained performance was reported by caregivers for those participants who continued in an 16-month extension. Performance on the NPI was equivalent to published findings at 3 to 6 months for donepezil and exceeded that of galantamine and their historical placebos. Participants demonstrated superior performance for more than 12 months in NPI and ADL versus those receiving naproxen and rofecoxib or their placebo group.
This formulation holds promise for treatment of early-stage Alzheimer's disease prior to and/or as a supplement for pharmacological approaches. (Chan et al., 2008)

Physician and caregiver ease of use/satisfaction scores, and assessments of cognition and ADL, showed significant benefits for donepezil compared with galantamine in a multinational, randomized, 12-week comparative trial. (Jones et al., 2004)
A study published in the International Journal of Geriatric Psychiatry compared directly, in the same patient cohort, the ease of use and tolerability of donepezil and galantamine in the treatment of Alzheimer's disease (AD), and investigated the effects of both treatments on cognition and activities of daily living (ADL). The Research Institute for the Care of the Elderly, St Martin's Hospital, Bath, UK conducted the study.
Patients with mild to moderate AD from 14 European centers were randomized to receive open-label donepezil (up to 10 mg once daily) or galantamine (up to 12 mg twice daily) for 12 weeks, according to the approved product labeling. Physicians and caregivers completed questionnaires rating satisfaction with treatment/ease of use in daily practice. Secondary assessments were the ADAS-cog, the MMSE, and the DAD scale to assess ADL. Tolerability was evaluated by reporting adverse events (AEs).
Both physicians and caregivers reported significantly greater overall satisfaction/ease of use for donepezil (n = 64) compared with galantamine (n = 56) at weeks 4, 12, and endpoint (week 12 LOCF; all p-values <0.05). Significantly greater improvements in cognition were also observed for donepezil versus galantamine on the ADAS-cog at Week 12 and endpoint (p-values <0.05). ADL improved significantly in the donepezil group compared with the galantamine group at weeks 4, 12, and endpoint (p-values <0.05). Most adverse events were mild to moderate, however, 46% galantamine-treated patients reported gastrointestinal adverse events vs 25% donepezil patients.
Physician and caregiver ease of use/satisfaction scores, and assessments of cognition and ADL, showed significant benefits for donepezil compared with galantamine in this direct comparative trial. Both treatments were well tolerated, with more gastrointestinal adverse events reported for galantamine vs donepezil. (Jones et al., 2004)

 

Dr. Ron

 


Articles

 

Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension.
            (Chan et al., 2008)  Download
We examined the efficacy of a vitamin/nutriceutical formulation (folate, vitamin B6, alpha-tocopherol, S-adenosyl methionine, N-acetyl cysteine, and acetyl-L-carnitine) in a 12-month, open-label trial with 14 community-dwelling individuals with early-stage Alzheimer's disease. Participants improved in the Dementia Rating Scale and Clock-drawing tests (Clox 1 and 2). Family caregivers reported improvement in multiple domains of the Neuropsychiatric Inventory (NPI) and maintenance of performance in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADL). Sustained performance was reported by caregivers for those participants who continued in an 16-month extension. Performance on the NPI was equivalent to published findings at 3 to 6 months for donepezil and exceeded that of galantamine and their historical placebos. Participants demonstrated superior performance for more than 12 months in NPI and ADL versus those receiving naproxen and rofecoxib or their placebo group. This formulation holds promise for treatment of early-stage Alzheimer's disease prior to and/or as a supplement for pharmacological approaches. A larger, placebo-controlled trial is warranted.

A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer's disease.
            (Jones et al., 2004)  Download
OBJECTIVES:  To compare directly, in the same patient cohort, the ease of use and tolerability of donepezil and galantamine in the treatment of Alzheimer's disease (AD), and investigate the effects of both treatments on cognition and activities of daily living (ADL). METHODS:  Patients with mild to moderate AD from 14 European centres were randomised to receive open-label donepezil (up to 10 mg once daily) or galantamine (up to 12 mg twice daily) for 12 weeks, according to the approved product labelling. Physicians and caregivers completed questionnaires rating satisfaction with treatment/ease of use in daily practice. Secondary assessments were the ADAS-cog, the MMSE, and the DAD scale to assess ADL. Tolerability was evaluated by reporting adverse events (AEs). RESULTS:  Both physicians and caregivers reported significantly greater overall satisfaction/ease of use for donepezil (n = 64) compared with galantamine (n = 56) at weeks 4, 12, and endpoint (week 12 LOCF; all p-values <0.05). Significantly greater improvements in cognition were also observed for donepezil versus galantamine on the ADAS-cog at Week 12 and endpoint (p-values <0.05). ADL improved significantly in the donepezil group compared with the galantamine group at weeks 4, 12, and endpoint (p-values <0.05). Most AEs were mild to moderate, however, 46% galantamine-treated patients reported gastrointestinal AEs vs 25% donepezil patients. CONCLUSIONS:  Physician and caregiver ease of use/satisfaction scores, and assessments of cognition and ADL, showed significant benefits for donepezil compared with galantamine in this direct comparative trial. Both treatments were well tolerated, with more gastrointestinal AEs reported for galantamine vs donepezil.

A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease.
            (Remington et al., 2015)  Download
BACKGROUND:  Increasing evidence points toward the efficacy of nutritional modifications in delaying cognitive decline and mood/behavioral difficulties in Alzheimer's disease (AD). Nutritional supplementation with individual agents has shown varied results suggesting the need for combinatorial intervention. OBJECTIVE:  We set out to determine whether nutritional intervention could positively impact cognitive performance and behavioral difficulties for individuals diagnosed with AD. METHODS:  A double-blind, multi-site, phase II study (ClinicalTrials.gov NCT01320527; Alzheimer's Association Trialmatch) was conducted in which 106 individuals with AD were randomized to a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open-label extension where participants received NF for 6 additional months. RESULTS:  The NF cohort improved versus the placebo cohort within 3 months (Clox-1 p = 0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722, 2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric Inventory. Both cohorts improved or maintained baseline performance during open-label extensions. Activities of Daily Living did not change for either cohort. CONCLUSIONS:  These findings extend phase I studies where NF maintained or improved cognitive performance and mood/behavior.

References

Chan, A, et al. (2008), ‘Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a 1-year, open-label pilot study with an 16-month caregiver extension.’, Am J Alzheimers Dis Other Demen, 23 (6), 571-85. PubMed: 19047474
Jones, RW, et al. (2004), ‘A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer’s disease.’, Int J Geriatr Psychiatry, 19 (1), 58-67. PubMed: 14716700
Remington, R, et al. (2015), ‘A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer’s Disease.’, J Alzheimers Dis, 45 (2), 395-405. PubMed: 25589719