Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco .
MAYWOOD, Ill., Having a drink only occasionally may reduce the risk of dementia, perhaps because long exposure to low alcohol levels help brain cells survive other stresses, researchers here said.
Most studies that have sought to compare drinking patterns with risk factors associated with dementia have found that moderate drinkers generally have a lower risk, according to Michael A. Collins, Ph.D., of Loyola University Chicago, and colleagues.
Yet their literature review of cardiovascular and neurological effects of ethanol, published online in Alcoholism: Clinical and Experimental Research, outlined a potential neuroprotective mechanism that light-to-moderate drinking could induce.
It was derived from a variety of preclinical studies of a phenomenon known as alcohol preconditioning.
In an interview, Dr. Collins said it was analogous to ischemic preconditioning, in which exposing brain neurons to a brief period of hypoxia helps them survive later bouts of more severe ischemia, such as would occur in a stroke.
These studies have shown that neurons in vitro temporarily dosed with low levels of ethanol can survive stresses that kill untreated neurons.
Dr. Collins said the mechanism appears to involve a sensor-transducer pathway, in which focal adhesion kinase and certain protein kinase C species are activated following low-dose alcohol exposure, which in turn generates two heat shock proteins, Hsp27 and Hsp70.
These latter proteins are well-known to protect cells from stress.
The likelihood of a direct neuroprotective mechanism is boosted by laboratory studies with two known neurotoxic agents, gp120 and beta-amyloid protein. The latter is believed to play a role in Alzheimer's disease, while gp120 is responsible for HIV dementia.
Pretreatment with alcohol protected brain neurons from these agents in vitro, Dr. Collins said.
Whether the preconditioning model accurately reflects what goes on in the brains of human drinkers is uncertain, Dr. Collins acknowledged.
"It is nonetheless conceivable that light-to-moderate, stable alcohol ingestion over years exerts 'preconditioning-like' effects on glia and neurons," he and his colleagues wrote in their review.
Noting that millions of new cases of dementia are diagnosed annually, they added, "it seems imperative that as much as possible is learned about the apparent cytoprotective mechanisms engendered by low-moderate alcohol intake and levels."
The review covered more than 100 studies of the cardiovascular and neurological effects of ethanol. It summarized and updated the proceedings of a roundtable meeting organized and chaired by Dr. Collins in 2007.
Dr. Collins and colleagues noted that not all studies showed a decreased risk. Moreover, they said, many of the investigators who did find reduced risk factors attributed their findings to the hematologic and cardiovascular effects of alcohol, or of other components of alcoholic drinks such as resveratrol.
But the review also included a number of in vitro and animal studies suggesting that low-dose ethanol has direct neuroprotective effects.
"Light to moderate, non-binge alcohol intake . . . does no apparent harm to cognition during aging, even possibly reducing the risk of cognitive decline [and] dementia," Dr. Collins and colleagues said.
"Alcohol-related anti-inflammatory heat shock protein and protein kinase changes in the brain bear similarities to those elucidated in the heart, particularly with respect to protein kinase C and quite likely other signal transduction kinases," they added