Cholinergic treatments, such as donepezil, and glutamatergic medicine, such as memantine, frequently show partial efficacy in the treatment of Alzheimer's disease and mild cognitive impairment (MCI), whether prescribed alone or in combination.1 Cholinergic and glutamatergic pathways may not be the only deficient neuropsychiatric systems in Alzheimer's disease. Serotonergic, dopaminergic, noradrenergic, and other pathways also may be dysfunctional in Alzheimer's and MCI.
Nicotine enhances memory by its effect on specific nicotinic cholinergic receptors.2 In addition, nicotine has antianxiety and antidepressant properties, possibly due to associative pathways between nicotinic cholinergic and noncholinergic specialty neurons, such as GABA, 5-hydroxy-tryptamine, dopamine, and norepinephrine.3 Nicotine also improves learning and attention.4
Varenicline behaves like nicotine and is the new selective alpha4beta2 nicotinic cholinergic receptor partial agonist used to treat nicotine dependence, which may also improve attention and learning.5 A case of Alzheimer's that responded to the addition of varenicline is reported here.
Case report. Ms. A, a 72-year-old Caucasian woman, was referred by her son in June, 2006, for obsessive worrying, anxiety, depression, and mildly impaired memory. She met DSM-IV-TR criteria for cyclothymic disorder but not dementia. Her previous physician prescribed venlafaxine and donepezil for her mood disorder and MCI, respectively. Venlafaxine was raised to 300mg daily, gabapentin was started and eventually raised to 2,000mg daily, and donepezil was discontinued in favor of memantine 5mg, eventually raised to 20mg daily. She became euthymic and her MCI improved slightly for about 10 months, at which time Ms. A began setting two extra place settings for dinner every late afternoon, acting defensive, showing signs of irritability, and significant memory impairment, especially in the evening. She met DSM-IV-TR criteria for Alzheimer's disease, and varenicline 1mg was started at 3pm daily. Ms. A's husband was instructed to have his wife eat a low-acid snack with an eight-ounce glassful of water before taking the medicine. She resumed setting the correct two dinner settings within a few days; her memory and mood improved considerably; and she no longer met criteria for Alzheimer's. In addition, she downgraded to MCI for two weeks with no side effects reported. Her level of functioning continued to improve during the treatment month that followed; she spontaneously resumed processing the household laundry, a practice she had abandoned for more than two years. Ms. A's memory remained much improved after three months of treatment with varenicline.
Although the placebo effect is negligible, a therapeutic link between varenicline and Alzheimer's cannot be established with certainty in this case. This case report does suggest that the new nicotinic cholinergic partial agonist varenicline was useful in this individual and may be useful in the management of the memory deficits associated with Alzheimer's disease. Further investigation is warranted using larger numbers of subjects at various stations along the MCI-Alzheimer's continuum. Varenicline may be a novel treatment for the cognitive deficits associated with Alzheimer's, other types of dementia, and MCI. Additional clinical trials using varenicline may also help us better understand the currently unsolved neuropsychiatric maze underlying Alzheimer's and MCI.
With regards,
James A. Cocores, MD
Nutritional Neuropsychiatry
Southcoast Psychotherapy and
Education Associates
Boca Raton, Florida
References
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