A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease

Sano, Mary; Ernesto, Christopher; Thomas, Ronald G.; Klauber, Melville R.; Schafer, Kimberly; Grundman, Michael; Woodbury, Peter; Growdon, John H.; Cotman, Carl W.; Pfeiffer, Eric; Schneider, Lon S.; Thal, Leon J.

doi:10.1056/nejm199704243361704

Cited by 2,207 publications

(1,190 citation statements)

References 32 publications

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“…Protection against oxidative damage has already been demonstrated to slow the clinical progression of AD [28], and chelation therapy with the iron chelator desferrioxamine was able to reduce the disease progression in patients with sporadic AD [9]. The identification of this novel AD-related genetic determinant provides new insights into the pathogenesis of the disease, and may also contribute towards the diagnosis and treatment of individuals from families at risk of AD carrying HFE mutations.…”

Section: Discussionmentioning

confidence: 99%

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Sampietro

Caputo

Casatta

et al. 2001

Neurobiology of Aging

104

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NEUROBIOL AGING. In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 Ϯ 6.0 years versus 76.6 Ϯ 5.8 years of those who were homozygous for the wild-type allele (p ϭ 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged Ͻ70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70 -80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

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Section: Discussionmentioning

confidence: 99%

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Sampietro

Caputo

Casatta

et al. 2001

Neurobiology of Aging

104

View full text Add to dashboard Cite

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“…But these drugs only offer a symptomatic approach and are of limited effect in long term administration. Other drugs have been reported to at least delay the progression of AD, like indomethacin (McGeer and McGeer, 1999;Rogers et al, 1993), selegilin and vitamin E (Sano et al, 1997), suggesting that anti-inflammatory and antioxidant agents can be beneficial in the treatment of AD patients.…”

Section: Discussionmentioning

confidence: 99%

Alpha-lipoic acid as a new treatment option for Azheimer type dementia

Häger¹,

Marahrens²,

Kenklies³

et al. 2001

Archives of Gerontology and Geriatrics

167

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Oxidative stress and energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD), thus antioxidants with positive effects on glucose metabolism such as thioctic (a-lipoic) acid should exert positive effects in these patients. Therefore, 600 mg a-lipoic acid was given daily to nine patients with AD and related dementias (receiving a standard treatment with acetylcholinesterase inhibitors) in an open study over an observation period of, on avarage, 337 980 days. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (mini-mental state examination: MMSE and AD assessment scale, cognitive subscale: ADAScog). Despite the fact that this study was small and not randomized, this is the first indication that treatment with a-lipoic acid might be a successful 'neuroprotective' therapy option for AD and related dementias.

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“…Multiple preclinical studies on vitamin C and vitamin E using transgenic AD mouse models indicated decreased lipid peroxidation, memory deficits, and Aβ plaque burden [114][115][116]. However, clinically, vitamins C and E showed limited benefits on cognitive function or delay of AD progression [117][118][119]141]. Some studies indicated negative effects of high-dose vitamin E on cognitive function and increased risk for mortality [142].…”

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

2015

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Alzheimer's disease (AD) has a complex and progressive neurodegenerative phenotype, with hypometabolism and impaired mitochondrial bioenergetics among the earliest pathogenic events. Bioenergetic deficits are well documented in preclinical models of mammalian aging and AD, emerge early in the prodromal phase of AD, and in those at risk for AD. This review discusses the importance of early therapeutic intervention during the prodromal stage that precedes irreversible degeneration in AD. Mechanisms of action for current mitochondrial and bioenergetic therapeutics for AD broadly fall into the following categories: 1) glucose metabolism and substrate supply; 2) mitochondrial enhancers to potentiate energy production; 3) antioxidants to scavenge reactive oxygen species and reduce oxidative damage; 4) candidates that target apoptotic and mitophagy pathways to either remove damaged mitochondria or prevent neuronal death. Thus far, mitochondrial therapeutic strategies have shown promise at the preclinical stage but have had little-to-no success in clinical trials. Lessons learned from preclinical and clinical therapeutic studies are discussed. Understanding the bioenergetic adaptations that occur during aging and AD led us to focus on a systems biology approach that targets the bioenergetic system rather than a single component of this system. Bioenergetic system-level therapeutics personalized to bioenergetic phenotype would target bioenergetic deficits across the prodromal and clinical stages to prevent and delay progression of AD.

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A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease

Abstract: In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.

Cited by 2,207 publications

References 32 publications

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Alpha-lipoic acid as a new treatment option for Azheimer type dementia

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

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