This study demonstrated that heavy alcohol drinking in young-old people (60–69 years) was associated with a lower risk of cognitive impairment, while middle-old people (≧70 years) showed a higher risk of cognitive impairment than non-drinkers. This study also revealed that older adults (≧70 years), men, people from minority races, persons with lower education or income levels, people with difficulty attending social events, and those with hypertension or CKD were significantly associated with a higher risk of cognitive impairment.
Cognition refers to the mental functions involved in learning, memory, judgment, expression, and work [1, 15]. Some researchers have reported that older adults may be more susceptible to cognitive dysfunction due to brain aging and long-term cumulative injury [15, 19]. People with lower education levels may have less brain reserve and a higher risk of cognitive decline [1, 15, 20]. Ethnic minorities and people with low income or social difficulties and an inability to afford good food may have increased susceptibility to cognitive dysfunction [1, 15, 21]. People with hypertension or chronic kidney disease may have long-term inflammation and oxidative stress with a higher risk of cognitive impairment . Men may experience higher stress in daily activities without the protective effects of estrogen (seen in women), leading to a higher risk of cognitive decline [1, 15]. Our study also revealed that the abovementioned factors were associated with a higher risk of cognitive impairment.
Studies have shown that a low or moderate amount of alcohol consumption protects against cognitive impairment [4, 7, 8]. However, some studies show that low or moderate alcohol drinking has a neutral effect or a higher risk of cognitive impairment [9,10,11, 22]. The conflicting results could be because these studies used different tools to evaluate cognitive dysfunction; the definitions of the quantity and pattern of alcohol drinking, smoking status, educational and occupational attainment, comorbidities, and psychotropic drugs use of the drinkers and non-drinkers were different [4, 11]. However, the recent studies have indicated that a low or moderate amount of alcohol consumption is associated with a lower risk of cognitive impairment . These findings are consistent with our study result that low to moderate alcohol consumption was associated with a lower risk of cognitive impairment. The reasons are as follows: (1) low to moderate alcohol drinking can increase high-density lipoprotein (HDL) levels, decrease platelet aggregation, increase fibrinolysis, and inhibit thrombotic activity ; (2) alcohol drinking can reduce systemic inflammation and facilitate antioxidant effect ; (3) Moderate alcohol drinking was reported to increase the levels of brain-derived neurotrophic factor (a key regulator of neuronal plasticity and development) in the dorsal striatum . However, alcohol consumption can lead to liver disease, accidents, stroke, and cancers .
Studies show that heavy alcohol drinking may have direct or indirect detrimental effects on the brain [4, 11, 28]. First, acetaldehyde and reactive oxygen species (ROS) produced by alcohol metabolism can have toxicological concerns to the liver, gut and brain [5, 29, 30]. Alcohol metabolism can generate mitochondrial damage and hypoxia, make cells to undergo necrosis, apoptosis, and induce inflammation. ROS may lead to less antioxidants, breakdown of electron transport chain and reduced ATP production, mitochondrial membrane collapse and lysosomal membrane leakage, and ultimately cause cell injury or death . ROS also can stimulate the activation of nuclear factor-κB (NF-κB) and increase inflammation . Second, alcohol can modify the fluidity of cell membranes, interact with calcium and chlorine channels, and impair cell function. It acts on several neural networks served by different neurotransmitters . Third, alcohol can also block N-methyl-d-aspartate (NMDA) receptors. Chronic inhibition of NMDA receptors can increase glutamate release with excitotoxic effects on neurons [28, 31]. Fourth, malnutrition, thiamine deficiency, and other vitamin deficiencies can cause indirect neuronal damage . Fifth, heavy drinking can lead to hyperlipidemia, high blood pressure, increased risk of stroke, and brain injury . Finally, chronic alcohol consumption can impair the microbiota balance and barrier function of the gut, increase lipopolysaccride (LPS) translocation, decrease liver’s ability to detoxify bacterial products and engender an imbalance in cytokine milieu, abate the brain’s ability to regulate periphery inflammation, and give rise to persistent systemic inflammation and organ damage . However, there are still reports showing neutral or protective effects of heavy alcohol drinking against cognitive impairment [4, 11]. As we divided the older adults into young-old (60–69 years) and middle-old (≧70 years) groups, heavy alcohol drinking seemed to provide protective effects against cognitive impairment in young-old persons, with a higher risk of cognitive impairment in middle-old persons. But we must be careful that this is a cross-sectional study, we can only see association but not causality. Young-old people with heavy alcohol drinking may have be more financially capable. They can have a healthy diet with appropriate leisure activities, which can lead them to less cognition decline. It is also possible that the DSST may not be sensitive enough to detect cognitive impairment caused by heavy drinking in this study. Older adults showing an accumulation of various brain insults with time may be more vulnerable to the effects of heavy alcohol drinking [15, 18, 32, 33]. However, many older adults may have the habit of alcohol drinking  and it will be challenging to influence drinking behavior when there is long interval between risk-taking behaviors and the onset of complications. We should stress the importance of restricting alcohol use in middle-old people to decrease the risk of cognitive impairment.
Studies have demonstrated that the use of probiotics can improve gut permeability and attenuate tissue injury in patients or animals with alcoholic liver diseases. We may suggest probiotics for older people with heavy drink to potentially mitigate inflammation . Oxidative stress occurs when the endogenous antioxidant defenses are unable to eliminate excessive ROS. Older adults have insufficient antioxidant defense and may not be able to eliminate the excess production of ROS by heavy drinking with the susceptibility to cognitive decline . Eftekhari and Ahmadian, et al. have performed exquisite researches to demonstrate that antioxidants (N-acetylcysteine, quercetine, and taurine), ROS scavengers (a-tocopherol succinate and/or butylated hydroxyltoluene), ATP generators (fructose and/r l-glutamine), mitochondrial permeability transition (MPT) pore sealing agents (carnitine and/or trifluoperazine), endocytosis inhibitors (chloroquine and/or methylamine), and CYP450 inhibitors (4-methylpyrazole and/or cimetidine) can prevent medication-induced oxidative stress cytotoxicity [36, 37]. We may advise the elderly to consume more unprocessed vegetables, fruits, fish and meats to increase the natural antioxidants. But because the older people have bad teeth. Their absorption of nutrients is not good. They may need to supplement antioxidant medications. Due to poor water solubility, slow permeability, gastrointestinal degradation, first-pass effect, and instability during storage, most antioxidants have not been used successfully. This problem may be solved by adopting the nanomedicine, that is to encapsulate or process the antioxidants as nanoparticles. These options can increase the solubility, permeability and preservation of nano-antioxidants, also enhance their surface area, uptake and transport to the target sites; which will work to improve intracellular penetration and distribution of the nano-antioxidants. Nanocapsulated quercetin (a flavonoid) has been demonstrated to reduce the oxidative stress of brain damage caused by arsenic exposure . We may suggest older people to take nano-antioxidants to plummet the oxidative stress and combat the cognitive dysfunction caused by heavy alcohol drinking.
Some limitations in this study need to be stated. First, as NHANES data analysis was cross-sectional in design, we could not determine the duration, pattern, and frequency of alcohol drinking. The assessment of alcohol consumption was based on self-report instead of objective measures, and therefore, may be subject to bias; however, current evidence reveals that this may be a reliable and valid approach to measure alcohol consumption . Second, the NHANES examined persons dwelling in the community, not institutions. The community-dwelling older adults may be healthier than nursing home residents; therefore, our results may underestimate the risk of cognitive impairment. Third, we excluded subjects who could not complete DSST assessments, or those individuals who could not enroll in surveys. Thus, those who participated in the NHANES were relatively healthy or resistant to the toxic effects of alcohol. Fourth, we used the DSST to assess cognitive impairment, which is sensitive to cognitive decline . However, this test alone may not provide insights into different domains of cognitive processing. Fifth, this dataset lacks information on apolipoprotein Eɛ4 (APOE E4) , alcohol dehydrogenase 1B (ADH1B), and acetaldehyde dehydrogenase 2 (ALDH2) genes, and therefore, we did not include these 3 genes as variables in the analysis. Sixth, the results of this study apply to the American population and may not apply to other countries. Finally, this is a cross-sectional study with some inevitable bias. Prospective randomized control trials are needed to verify our results.