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Association between alcohol and Alzheimer's disease (Review)

  • Authors:
    • Wen-Juan Huang
    • Xia Zhang
    • Wei-Wei Chen
  • View Affiliations

  • Published online on: June 14, 2016
  • Pages: 1247-1250
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by dense deposition of amyloid-β (Aβ) protein in the brain, failure of the memory and dementia. At present, there is no cure for AD and current treatments only provide a temporary reduction of symptoms. Thus, there is a need for effective preventive/curative strategic approaches. Accordingly, epidemiological studies have reported a reduction in the prevalence of AD in individuals ingesting low amounts of alcohol, while a moderate consumption of ethanol may protect against Aβ. These data are conflicting with other observations that assigned detrimental effects of heavy alcohol use on brain function, which are apparently similar to those observed in AD. These discrepancies questioned whether or not alcohol is a protective agent against the development of AD, whether the probable protective effects are influenced by the quantity and/or frequency of drinking. These issues are addressed in this review with the aim to suggest the real risk of alcohol for developing or preventing AD.


Alzheimer's disease (AD), the most common form of dementia affecting populations aged over 65 years worldwide, is sporadic, genetically non-obvious, and rarely inherited (1). The main well-known pathological features of the disease include the abnormal extracellular deposition of misfolded amyloid-β (Aβ) senile plaques in brain parenchyma and cerebral vessels, the intracellular accumulation of hyperphosphorylated tau (τ) in neurofibrillary tangles (NFTs), chronic neuroinflammation, neuronal loss and severe brain atrophy as well as progressive loss of memory (2,3). Consequently, in the last 30 years, the deregulation of Aβ metabolism (oligomerization, aggregation and plaque formation) has been the major target for therapeutic intervention (4), and only marginal effects have been registered (57), suggesting the need for preventive/curative treatments or alternative solutions.

Therefore, although the causes of AD remain unknown and cures or universally effective treatments, are not available, most experts have highlighted a broad constellation of contributing risk factors. Among these risk factors, alcohol consumption, associated with extensive cognitive problems (8), including alcoholic dementia (9), has been targeted. Similar features have been denoted between the effects of alcohol on cognition, brain disorder and brain biochemistry with the biological effects of AD, suggesting that the use of alcohol may constitute a risk for aggravating or developing AD (10). In line with this view, AD patients with a habitual drinking history have shown cognitive improvement during the clinical course of abstinence (11). By contrast, this effect was not observed in patients consuming high amounts of alcohol prior to diagnosis of AD (11). In line with these data, there is another emerging body of literature that contends alcohol consumption, particularly red wine, may rather serve as a protective factor for cognitive decline (12,13). Several epidemiological studies have shown that low or moderate wine consumption can be effective in retarding age-related cognitive decline (14), possibly linked to polyphenols present in beverages.

However, the studies promoting the benefits of alcohol on AD exclusively focus on moderate alcohol consumption (12), the restriction of alcohol to only an elderly population (13), and broad classification of cognitive decline (15). Relevant issues remained regarding the protection, the aggravating or detrimental effects of alcohol consumption or whether protective effects are simply influenced by the quantity and/or frequency of drinking. Despite the limiting factors identified regarding the beneficial effects of alcohol consumption (16), a single-target therapeutic strategy appears to produce only suboptimal results and a broader neuroprotective approach, at least theoretically, appears more appealing (17). Thus, the aim of the present review was to discuss the association between alcohol consumption and AD.

Alcohol consumption as a risk factor for developing AD

Heavy alcohol consumption impairs cognitive performance with immediate and long-term effects on the brain anatomy and neuropsychological functioning (1821). Cognitive impairment is related to clinical dementia as it accelerates shrinkage and atrophy of the brain, leading to critical determinant of neurodegenerative changes and cognitive decline in aging (22). However, these morphological changes induced by alcohol consumption may be reversible unlike AD or aging (23), as atrophy decreases, with cognitive improvement after abstinence from alcohol (24,25). Other data showed that morphological changes in the brain are associated with the loss of a number of nerve cells occurring in the white matter, which largely comprises nerve fibers that connect neurons (26) and/or cortical cholinergic neurons (24), known to be affected in AD. This link renders plausible that alcohol use may be linked to AD as the cholinergic system plays an important role in memory. This role is confirmed and its deficits are well established in AD (27). Chronic alcohol use causes degeneration of cholinergic neurons (28), or decreases receptors of cholinergic system in AD. These may aggravate the reduction of cholinergic neurons already present in AD patients. However, the improvement of cognitive function in alcoholics after abstention from alcohol suggests that cognitive deficits may reflect neurochemical alterations rather than neuronal loss (24,28). Therefore, without appearing as an accelerator of AD process, alcohol may induce its effects on the cholinergic system, independently from the cholinergic deficits caused by AD (29,30). However, alcohol-related brain damage appears to differ in young and older alcohol consumers (24), although data suggest that alcohol abuse may accelerate aging-related changes in the brain at any age and that older adults may be more vulnerable to the effects of alcohol (8). Apart from cholinergic deficit, another negative effect of heavy alcohol consumption on cognitive function may be attributed to nutritional deficiency or vascular change (31,32), which consist of damage that may be relatively irreversible even after abstinence from heavy alcohol consumption (11).

Therefore, despite the above evidence showing cognitive detrimental effects of heavy alcohol consumption, to the best of our knowledge, no study has established a clear association between alcohol consumption and AD (33). More consistently, recent genetical study on a Japanese population provided evidence that the mitochondrial aldehyde dehydrogenase 2 (ALDH2*2, metabolizes acetaldehyde into acetate, protecting against oxidative stress and playing an important role in the development of AD), and two functional single-nucleotide polymorphisms (SNPs) of the dopamine-β-hydroxylase (DBH) gene, involved in the pathophysiology of alcoholism and whose activity is reduced in the neocortex of AD), did not modify the risk for developing AD, suggesting that the polymorphism of the ALDH2 and DBH genes were not associated with AD (34). Nevertheless, future studies must be undertaken on other populations worldwide.

Potential benefits of alcohol on AD

Low-to-moderate alcohol intake is considered to protect against neurodegeneration pathology (13,15), dementia (3539) and cognitive deterioration (4043). Of the biologic mechanisms suggested to explain such potential beneficial effects on the brain, there are mainly the antioxidant properties of wine flavonoids (44), the effects against Aβ (45) and the prevention of ischemia or stroke by alcohol (46). Specifically, polyphenols, members of a large family of plant-derived compounds, are molecules containing one or more phenolic group. There are thousands of polyphenols that have been identified thus far including, bioflavonoids (anthocyanins, flavanols, favanols, favones, flavanones, isofavones and proanthocyanins), coumestans, ligans and stilbenoids (47). Polyphenolics are in general antioxidant molecules that reduce the in vitro process aggregation of Aβ, reducing the neuronal death of cortical neurons preventing neurodegeneration (48). The morin for example, a specific flavonoid described in red wine exhibited significant effects in preventing aggregation of Aβ (49). In agreement with these data, red wine Cabernet Sauvignon significantly reduced the number of Aβ plaque-induced neuropathology and attenuated a spatial memory decrease in an adult Tg2576 mouse model of AD (50). Another flavonoid that plays an important role in red wine is resveratrol. Resveratrol is known to protect against cardiovascular diseases (which are risk factors for developing AD) and various types of cancer, together with the promotion of the antiaging effect, the modulation of pathomechanisms of debilitating neurological disorder such as strokes, ischemia and Huntington's disease, as well as protection against neuronal degeneration (14,51). Other natural molecules including fulvic acid, altered the aggregation mechanism of τ proteins, a critical protein involved in the stabilization of microtubule and axonal transport, found to be involved in AD pathogenesis (52). However, whatever the facts around the benefits that may follow the potential benefits of low-to-moderate consumption of alcohol, the importance of drinking patterns and specific beverages consumed remain elusive. The operational definition of low or moderate drinking which may vary greatly across studies (53) and the concept of a moderate drinker, which may also be imprecise, comprising a wide range measure that may include those consuming less than one drink a day (54). Red wine consumption appears to promote far more protective effects than the consumption of other ethanol containing beverages (55). This is in keeping with variations that may be introduced by consumers who sometimes associate the consumption of tobacco, or the possible toxicity effects of chronic exposure of the liver to alcohol (56), which can also contribute to brain alteration in regions involved in memory (57).

Taken together, the data provide insufficient evidence to suggest abstainers should initiate alcohol consumption to protect against dementia or AD.


Based on the abovementioned research data, no relationship between alcohol consumption and AD exists. In addition, although low-to-moderate consumption of alcohol may protect against AD, leading to benefits on neurodegeneration, Aβ, oxidative stress and τ neurofibrilary tangle formation suggest bias regarding the definition of low-to-moderate consumption as well as the variability of beverages containing alcohol. In addition, the absence of studies on the possible side effects of chronic exposure to alcohol on peripheral organs such as liver, and kidney lead to the necessity to delineate global and standard protocols for advanced studies. These studies render the benefits associated with low-to-moderate alcohol consumption against AD. However, the results should be considered as controversial and insufficient to suggest abstainers that initiate alcohol consumption in a preventive manner against AD.



Kumar A, Singh A and Ekavali E: A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 67:195–203. 2015. View Article : Google Scholar : PubMed/NCBI


Querfurth HW and LaFerla FM: Alzheimer's disease. N Engl J Med. 362:329–344. 2010. View Article : Google Scholar : PubMed/NCBI


Medeiros R and LaFerla FM: Astrocytes: conductors of the Alzheimer disease neuroinflammatory symphony. Exp Neurol. 239:133–138. 2013. View Article : Google Scholar : PubMed/NCBI


Mucke L and Selkoe DJ: Neurotoxicity of amyloid β-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med. 2:a0063382012. View Article : Google Scholar : PubMed/NCBI


Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, et al: Alzheimer's Disease Cooperative Study Steering Committee; Solanezumab Study Group: Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 370:311–321. 2014. View Article : Google Scholar : PubMed/NCBI


Krstic D and Knuesel I: Deciphering the mechanism underlying late-onset Alzheimer disease. Nat Rev Neurol. 9:25–34. 2013. View Article : Google Scholar : PubMed/NCBI


Reitz C, Conrad C, Roszkowski K, Rogers RS and Mayeux R: Effect of genetic variation in LRRTM3 on risk of Alzheimer disease. Arch Neurol. 69:894–900. 2012. View Article : Google Scholar : PubMed/NCBI


Evert DL and Oscar-Berman M: Alcohol-related cognitive impairments. Alcohol Health Res World. 19:891995.


Smith DM and Atkinson RM: Mood disorders secondary to drugs and pharmacologic agents. Semin Clin Neuropsychiatry. 2:285–295. 1997.PubMed/NCBI


Tyas SL: Are tobacco and alcohol use related to Alzheimer's disease? A critical assessment of the evidence and its implications. Addict Biol. 1:237–254. 1996. View Article : Google Scholar : PubMed/NCBI


Toda A, Tagata Y, Nakada T, Komatsu M, Shibata N and Arai H: Changes in Mini-Mental State Examination score in Alzheimer's disease patients after stopping habitual drinking. Psychogeriatrics. 13:94–98. 2013. View Article : Google Scholar : PubMed/NCBI


Neafsey EJ and Collins MA: Moderate alcohol consumption and cognitive risk. Neuropsychiatr Dis Treat. 7:465–484. 2011. View Article : Google Scholar : PubMed/NCBI


Peters R, Peters J, Warner J, Beckett N and Bulpitt C: Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 37:505–512. 2008. View Article : Google Scholar : PubMed/NCBI


Granzotto A and Zatta P: Resveratrol and Alzheimer's disease: Message in a bottle on red wine and cognition. Front Aging Neurosci. 6:952014. View Article : Google Scholar : PubMed/NCBI


Anstey KJ, Mack HA and Cherbuin N: Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatry. 17:542–555. 2009. View Article : Google Scholar : PubMed/NCBI


Panza F, Frisardi V, Seripa D, Logroscino G, Santamato A, Imbimbo BP, Scafato E, Pilotto A and Solfrizzi V: Alcohol consumption in mild cognitive impairment and dementia: harmful or neuroprotective? Int J Geriatr Psychiatry. 27:1218–1238. 2012. View Article : Google Scholar : PubMed/NCBI


Mudher A and Lovestone S: Alzheimer's disease - do tauists and baptists finally shake hands? Trends Neurosci. 25:22–26. 2002. View Article : Google Scholar : PubMed/NCBI


Ridderinkhof KR, de Vlugt Y, Bramlage A, Spaan M, Elton M, Snel J and Band GP: Alcohol consumption impairs detection of performance errors in mediofrontal cortex. Science. 298:2209–2211. 2002. View Article : Google Scholar : PubMed/NCBI


Zhu W, Volkow ND, Ma Y, Fowler JS and Wang G-J: Relationship between ethanol-induced changes in brain regional metabolism and its motor, behavioural and cognitive effects. Alcohol Alcohol. 39:53–58. 2004. View Article : Google Scholar : PubMed/NCBI


Oslin DW and Cary MS: Alcohol-related dementia: validation of diagnostic criteria. Am J Geriatr Psychiatry. 11:441–447. 2003. View Article : Google Scholar : PubMed/NCBI


Weissenborn R and Duka T: Acute alcohol effects on cognitive function in social drinkers: their relationship to drinking habits. Psychopharmacology (Berl). 165:306–312. 2003.PubMed/NCBI


Meyer JS, Terayama Y, Konno S, Akiyama H, Margishvili GM and Mortel KF: Risk factors for cerebral degenerative changes and dementia. Eur Neurol. 39(Suppl 1): 7–16. 1998. View Article : Google Scholar : PubMed/NCBI


Wilkinson DA and Poulos CX: The chronic effects of alcohol on memory. A contrast between a unitary and dual system approach. Recent Dev Alcohol. 5:5–26. 1987. View Article : Google Scholar : PubMed/NCBI


Kril JJ and Halliday GM: Brain shrinkage in alcoholics: a decade on and what have we learned? Prog Neurobiol. 58:381–387. 1999. View Article : Google Scholar : PubMed/NCBI


Reed LJ, Lasserson D, Marsden P, Stanhope N, Stevens T, Bello F, Kingsley D, Colchester A and Kopelman MD: FDG-PET findings in the Wernicke-Korsakoff syndrome. Cortex. 39:1027–1045. 2003. View Article : Google Scholar : PubMed/NCBI


Jensen GB and Pakkenberg B: Do alcoholics drink their neurons away? Lancet. 342:1201–1204. 1993. View Article : Google Scholar : PubMed/NCBI


Tyas SL: Alcohol use and the risk of developing Alzheimer's disease. Alcohol Res Health. 25:299–306. 2001.PubMed/NCBI


Arendt T: Impairment in memory function and neurodegenerative changes in the cholinergic basal forebrain system induced by chronic intake of ethanol. Cell and Animal Models in Aging and Dementia Research. Hoyer S, Müller D and Plaschke K: 44:Springer. (Vienna). 173–187. 1994.doi: 10.1007/978-3-7091-9350-1_13. View Article : Google Scholar


Freund G and Ballinger WE Jr: Alzheimer's disease and alcoholism: possible interactions. Alcohol. 9:233–240. 1992. View Article : Google Scholar : PubMed/NCBI


Diamond I and Gordon AS: Cellular and molecular neuroscience of alcoholism. Physiol Rev. 77:1–20. 1997.PubMed/NCBI


Harper C and Matsumoto I: Ethanol and brain damage. Curr Opin Pharmacol. 5:73–78. 2005. View Article : Google Scholar : PubMed/NCBI


Schmidt KS, Gallo JL, Ferri C, Giovannetti T, Sestito N, Libon DJ and Schmidt PS: The neuropsychological profile of alcohol-related dementia suggests cortical and subcortical pathology. Dement Geriatr Cogn Disord. 20:286–291. 2005. View Article : Google Scholar : PubMed/NCBI


Piazza-Gardner AK, Gaffud TJ and Barry AE: The impact of alcohol on Alzheimer's disease: a systematic review. Aging Ment Health. 17:133–146. 2013. View Article : Google Scholar : PubMed/NCBI


Komatsu M, Shibata N, Ohnuma T, Kuerban B, Tomson K, Toda A, Tagata Y, Nakada T, Shimazaki H and Arai H: Polymorphisms in the aldehyde dehydrogenase 2 and dopamine β hydroxylase genes are not associated with Alzheimer's disease. J Neural Transm Vienna. 121:427–432. 2014. View Article : Google Scholar : PubMed/NCBI


Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S and Breteler MB: Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris). 153:185–192. 1997.PubMed/NCBI


Truelsen T, Thudium D and Grønbaek M: Copenhagen City Heart Study: Amount and type of alcohol and risk of dementia: The Copenhagen City Heart Study. Neurology. 59:1313–1319. 2002. View Article : Google Scholar : PubMed/NCBI


Huang W, Qiu C, Winblad B and Fratiglioni L: Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. J Clin Epidemiol. 55:959–964. 2002. View Article : Google Scholar : PubMed/NCBI


Luchsinger JA, Tang MX, Siddiqui M, Shea S and Mayeux R: Alcohol intake and risk of dementia. J Am Geriatr Soc. 52:540–546. 2004. View Article : Google Scholar : PubMed/NCBI


Mukamal KJ, Kuller LH, Fitzpatrick AL, Longstreth WT Jr, Mittleman MA and Siscovick DS: Prospective study of alcohol consumption and risk of dementia in older adults. JAMA. 289:1405–1413. 2003. View Article : Google Scholar : PubMed/NCBI


Cervilla JA, Prince M and Mann A: Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project. J Neurol Neurosurg Psychiatry. 68:622–626. 2000. View Article : Google Scholar : PubMed/NCBI


Christian JC, Reed T, Carmelli D, Page WF, Norton JA Jr and Breitner JC: Self-reported alcohol intake and cognition in aging twins. J Stud Alcohol. 56:414–416. 1995. View Article : Google Scholar : PubMed/NCBI


Leroi I, Sheppard J-M and Lyketsos CG: Cognitive function after 11.5 years of alcohol use: relation to alcohol use. Am J Epidemiol. 156:747–752. 2002. View Article : Google Scholar : PubMed/NCBI


Zuccalà G, Onder G, Pedone C, Cesari M, Landi F, Bernabei R and Cocchi A: Gruppo Italiano di Farmacoepidemiologia nell'Anziano Investigators: Dose-related impact of alcohol consumption on cognitive function in advanced age: results of a multicenter survey. Alcohol Clin Exp Res. 25:1743–1748. 2001. View Article : Google Scholar : PubMed/NCBI


Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P and Dartigues J-F: Intake of flavonoids and risk of dementia. Eur J Epidemiol. 16:357–363. 2000. View Article : Google Scholar : PubMed/NCBI


Ho L, Chen LH, Wang J, Zhao W, Talcott ST, Ono K, Teplow D, Humala N, Cheng A, Percival SS, et al: Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer's disease-type neuropathology and cognitive deterioration. J Alzheimers Dis. 16:59–72. 2009.PubMed/NCBI


Berger K, Ajani UA, Kase CS, Gaziano JM, Buring JE, Glynn RJ and Hennekens CH: Light-to-moderate alcohol consumption and risk of stroke among U.S. male physicians. N Engl J Med. 341:1557–1564. 1999. View Article : Google Scholar : PubMed/NCBI


Pasinetti GM: Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications. Planta Med. 78:1614–1619. 2012. View Article : Google Scholar : PubMed/NCBI


Kang I-J, Jeon YE, Yin XF, Nam J-S, You SG, Hong MS, Jang BG and Kim M-J: Butanol extract of Ecklonia cava prevents production and aggregation of beta-amyloid, and reduces beta-amyloid mediated neuronal death. Food Chem Toxicol. 49:2252–2259. 2011. View Article : Google Scholar : PubMed/NCBI


Noor H, Cao P and Raleigh DP: Morin hydrate inhibits amyloid formation by islet amyloid polypeptide and disaggregates amyloid fibers. Protein Sci. 21:373–382. 2012. View Article : Google Scholar : PubMed/NCBI


Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST and Pasinetti GM: Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB J. 20:2313–2320. 2006. View Article : Google Scholar : PubMed/NCBI


Anekonda TS: Resveratrol - a boon for treating Alzheimer's disease? Brain Res Brain Res Rev. 52:316–326. 2006. View Article : Google Scholar


Cornejo A, Jiménez JM, Caballero L, Melo F and Maccioni RB: Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer's disease. J Alzheimers Dis. 27:143–153. 2011.PubMed/NCBI


Ganguli M, Vander Bilt J, Saxton JA, Shen C and Dodge HH: Alcohol consumption and cognitive function in late life: a longitudinal community study. Neurology. 65:1210–1217. 2005. View Article : Google Scholar : PubMed/NCBI


Reid MC, Van Ness PH, Hawkins KA, Towle V, Concato J and Guo Z: Light to moderate alcohol consumption is associated with better cognitive function among older male veterans receiving primary care. J Geriatr Psychiatry Neurol. 19:98–105. 2006. View Article : Google Scholar : PubMed/NCBI


Baur JA and Sinclair DA: Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 5:493–506. 2006. View Article : Google Scholar : PubMed/NCBI


Sun Q, Long Z, Wu H, Liu Y, Wang L, Zhang X, Wang X and Hai C: Effect of alcohol on diethylnitrosamine-induced hepatic toxicity: critical role of ROS, lipid accumulation, and mitochondrial dysfunction. Exp Toxicol Pathol. 67:491–498. 2015. View Article : Google Scholar : PubMed/NCBI


Matsumoto H and Matsumoto I: Alcoholism: protein expression profiles in a human hippocampal model. Expert Rev Proteomics. 5:321–331. 2008. View Article : Google Scholar : PubMed/NCBI

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Huang, W., Zhang, X., & Chen, W. (2016). Association between alcohol and Alzheimer's disease (Review). Experimental and Therapeutic Medicine, 12, 1247-1250.
Huang, W., Zhang, X., Chen, W."Association between alcohol and Alzheimer's disease (Review)". Experimental and Therapeutic Medicine 12.3 (2016): 1247-1250.
Huang, W., Zhang, X., Chen, W."Association between alcohol and Alzheimer's disease (Review)". Experimental and Therapeutic Medicine 12, no. 3 (2016): 1247-1250.