Anti-inflammatory drugs for treatment and prevention of Alzheimer’s disease have to date proved disappointing, including a large study of low-dose prednisone, but higher dose steroids significantly reduced amyloid secretion in a small series of nondemented patients. In addition, there is a case report of a patient with amyloid angiopathy who had complete remission from two doses of dexamethasone, and very high dose steroids are already used for systemic amyloidosis. This paper presents the hypothesis that pulse-dosed intrathecal methylprednisolone or dexamethasone will produce detectable slowing of Alzheimer’s progression, additive to that obtained with cholinesterase inhibitors and memantine. A protocol based on treatment regimens for multiple sclerosis and central nervous system lupus is outlined, to serve as a basis for formulating clinical trials. Ultimately intrathecal corticosteroids might become part of a multi-agent regimen for Alzheimer’s disease and also have application for other neurodegenerative disorders.
Epidemiological evidence suggests that drugs which counteract inflammation might have efficacy for the prevention and treatment of Alzheimer’s disease, but up to now clinical trials have failed to show any clear-cut benefits for nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, anti-leprosy agents or prednisone. In the case of prednisone, however, it may be that much higher doses might be effective where lower doses were not. In the largest clinical trial to date, patients were given prednisone starting at 20 mg per day for one month, followed by one year at 10 mg daily and then tapering off over another 4 months. By contrast, in a series of 16 nondemented patients aged 25 to 82 who were given prednisolone 30–60 mg per day for at least month for treatment of various conditions, there was significant reduction in cerebrospinal fluid amyloid beta peptides in 15 out of 16 patients, up to about a 50% decline for patients receiving 50 and 60 mg of prednisolone. If amyloid is indeed a cause of Alzheimer’s disease, the above data suggests high dose steroids could suppress Alzheimer’s disease by reducing amyloid.
If the above line of reasoning is on the right track, it is important to note that high dose corticosteroids are already used clinically for treatment of primary systemic amyloidosis, in amounts orders of magnitude greater than those used in the Alzheimer’s disease trial. For example, in one recently published study of a regimen combining dexamethasone and interferon, patients were given several days of dexamethasone in an amount of 40 mg per day, which would be equivalent to 400 mg of prednisone daily.
Finally, there is a case report of a 64-year-old man with multiple myeloma who had a temporary remission of Alzheimer’s disease while receiving chemotherapy with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone.
Obviously megadose of anabolic steroids or cytotoxic chemotherapy as a treatment for Alzheimer’s disease would be hard to justify, but if one can knock down amyloid production, inflammation or both with corticosteroids alone, there should be at least some therapeutic effects. The key is delivering high enough doses of corticosteroids to have efficacy without devastating or killing patients with steroid-induced side effects in the process. Building on several case reports of patients with central nervous system lupus erythematosus and multiple sclerosis who responded to intrathecal prednisolone, dexamethasone, or triamcinalone after failing oral and intravenous steroids, this paper proposes that a similar therapeutic strategy could be pursued for patients with Alzheimer’s disease. Studies in rhesus monkeys and pigs indicate that that intrathecal steroids maximize biodistribution within the brain and minimize it within the rest of the body.
Epidemiological evidence suggests that drugs which counteract inflammation might have efficacy for the prevention and treatment of Alzheimer’s disease, but up to now clinical trials have failed to show any clear-cut benefits for nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, anti-leprosy agents or prednisone. In the case of prednisone, however, it may be that much higher doses might be effective where lower doses were not. In the largest clinical trial to date, patients were given prednisone starting at 20 mg per day for one month, followed by one year at 10 mg daily and then tapering off over another 4 months. By contrast, in a series of 16 nondemented patients aged 25 to 82 who were given prednisolone 30–60 mg per day for at least month for treatment of various conditions, there was significant reduction in cerebrospinal fluid amyloid beta peptides in 15 out of 16 patients, up to about a 50% decline for patients receiving 50 and 60 mg of prednisolone. If amyloid is indeed a cause of Alzheimer’s disease, the above data suggests high dose steroids could suppress Alzheimer’s disease by reducing amyloid.
If the above line of reasoning is on the right track, it is important to note that high dose corticosteroids are already used clinically for treatment of primary systemic amyloidosis, in amounts orders of magnitude greater than those used in the Alzheimer’s disease trial. For example, in one recently published study of a regimen combining dexamethasone and interferon, patients were given several days of dexamethasone in an amount of 40 mg per day, which would be equivalent to 400 mg of prednisone daily.
Finally, there is a case report of a 64-year-old man with multiple myeloma who had a temporary remission of Alzheimer’s disease while receiving chemotherapy with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone.
Obviously megadose of anabolic steroids or cytotoxic chemotherapy as a treatment for Alzheimer’s disease would be hard to justify, but if one can knock down amyloid production, inflammation or both with corticosteroids alone, there should be at least some therapeutic effects. The key is delivering high enough doses of corticosteroids to have efficacy without devastating or killing patients with steroid-induced side effects in the process. Building on several case reports of patients with central nervous system lupus erythematosus and multiple sclerosis who responded to intrathecal prednisolone, dexamethasone, or triamcinalone after failing oral and intravenous steroids, this paper proposes that a similar therapeutic strategy could be pursued for patients with Alzheimer’s disease. Studies in rhesus monkeys and pigs indicate that that intrathecal steroids maximize biodistribution within the brain and minimize it within the rest of the body.
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