There is a long-established relationship between alcohol use disorders, cognitive impairments, and the development of dementia. Studies have shown that heavy alcohol use in middle aged individuals impairs cognitive function even in patients who are not diagnosed with dementia (Giovanni Piumatti, 2018; Katherine Stavro, 2012). Traditionally, the study of neurocognitive impairments in alcoholics have focused on thiamine deficiency resulting in Wernicke encephalopathy or Wernicke-Korsakoff syndrome. More recently, evidence has begun to arise linking alcohol use disorders with other types of dementia including Alzheimer?s disease. Recent epidemiological data suggests that the hazard ratio to develop Alzheimer?s disease is 2-fold greater amongst individuals with alcohol use disorders compared to the general population (Michael Schwarsinger, 2018). This relationship is especially strong when alcohol abuse is examined as a risk factor for the onset of dementia in women and middle-aged adults. These epidemiological data suggest that the ?at risk? period to develop dementia is shifted to the middle-age years in individuals with alcohol use disorder. Consistent with this notion alcohol consuming rodents relative to controls show an increase in the expression of several proteins (such as b-amyloid precursor protein, C-terminal fragment-b, enzyme b-secretase 1, immature nicastrin, etc.,) that are involved in the synthesis of beta-amyloid plaques (Ab). However, the only post-mortem study that examined this issue in humans found no significant increase in the aggregation of Ab, hyperphosphorylated ?, or ?-synuclein in alcoholics compared to controls (Leena Aho, 2009). Given the retrospective nature of postmortem studies and the fact it cannot exclude co- morbid medical, psychiatric, and drug abuse disorders, it is difficult to interpret these data. There is a great need for in vivo studies to further investigate the relationship between alcohol use disorders, Ab, and Alzheimer?s disease. The positron emission tomography (PET) radiotracer [11C]PiB, which was discovered at the University of Pittsburgh is one of the most widely used and well validated Ab imaging agents (Klunk et al., 2004). Here, we propose to use [11C]PiB and PET to contrast the rate (%) of Ab positivity (+) in 40-65 year old alcoholics and controls. We hypothesize increased Ab+ in alcoholics compared to controls. Such a finding would suggest an increased risk of Ab+, and by extension explain the increased rates of Alzheimer?s dementia in alcoholics reported in recent epidemiological studies.
Here, we propose to use [11C]PiB and PET to contrast the rate (%) of Ab positivity (+) in 40-65 year old alcoholics and controls. We hypothesize increased Ab+ in alcoholics compared to controls. Such a finding would suggest an increased risk of Ab+, and by extension explain the increased rates of Alzheimer?s dementia in alcoholics reported in recent epidemiological studies.
| Narendran, Rajesh; Ciccocioppo, Roberto; Lopresti, Brian et al. (2018) Nociceptin Receptors in Alcohol Use Disorders: A Positron Emission Tomography Study Using [11C]NOP-1A. Biol Psychiatry 84:708-714 |
