Abstract
Alcohol consumption triggers a neuroinflammatory response which, if prolonged, can lead to substantial volume loss in both gray and white matter. This brain injury is associated with characteristic cognitive deficits, and, in extreme cases, with dementia. Even mild cognitive impairment creates a significant hurdle for alcohol rehabilitation, because the domains that are affected tend to be those important for sustaining abstinence. Thus, cognitive decline induced by alcohol contributes to the persistence of alcoholism. Here, I present converging data from animal and clinical studies that show how alcohol affects the brain and behavior. Although there is currently no targeted treatment for overcoming alcohol-induced cognitive decline, emerging evidence suggests that physical activity is both protective and restorative. This is a potential avenue for future programs targeted at treating alcohol abuse.
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References
Aharonovich E (2003) Cognitive impairment, retention and abstinence among cocaine abusers in cognitive-behavioral treatment. Drug Alcohol Depend 71(2):207–211
Aharonovich E, Hasin DS, Brooks AC, Liu X, Bisaga A, Nunes EV (2006) Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug Alcohol Depend 81(3):313–322
Baker KG, Harding AJ, Halliday GM, Kril JJ, Harper CG (1999) Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neuroscience 91(2):429–438
Bates ME, Bowden SC, Barry D (2002) Neurocognitive impairment associated with alcohol use disorders: implications for treatment. Exp Clin Psychopharmacol 10(3):193–212
Bates ME, Pawlak AP, Tonigan JS, Buckman JF (2006) Cognitive impairment influences drinking outcome by altering therapeutic mechanisms of change. Psychol Addict Behav 20(3):241–253
Bell SP, Dutta A (2002) DNA replication in eukaryotic cells. Annu Rev Biochem 71:333–374
Blume AW, Davis JM, Schmaling KB (1999) Neurocognitive dysfunction in dually-diagnosed patients: a potential roadblock to motivating behavior change. J Psychoactive Drugs 31(2):111–115
Brady KT, Gray KM, Tolliver BK (2011) Cognitive enhancers in the treatment of substance use disorders: clinical evidence. Pharmacol Biochem Behav 99(2):285–294
Brown RA, Abrantes AM, Minami H, Read JP, Marcus BH, Jakicic JM, Strong DR, Dubreuil ME, Gordon AA, Ramsey SE, Kahler CW, Stuart GL (2014) A preliminary, randomized trial of aerobic exercise for alcohol dependence. J Subst Abuse Treat 47(1):1–9
Cardenas VA, Durazzo TC, Gazdzinski S, Mon A, Studholme C, Meyerhoff DJ (2011) Brain morphology at entry into treatment for alcohol dependence is related to relapse propensity. Biol Psychiatry 70(6):561–567
Cations M, Withall A, Low LF, Draper B (2016) What is the role of modifiable environmental and lifestyle risk factors in young onset dementia? Eur J Epidemiol 31(2):107–124
Crews FT, Boettiger CA (2009) Impulsivity, frontal lobes and risk for addiction. Pharmacol Biochem Behav 93(3):237–247
Crews FT, Nixon K (2009) Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol 44(2):115–127
Crews FT, Buckley T, Dodd PR, Ende G, Foley N, Harper C, Sullivan EV (2005) Alcoholic neurobiology: changes in dependence and recovery. Alcohol Clin Exp Res 29(8):1504–1513
Crews FT, Collins MA, Dlugos C, Littleton J, Wilkins L, Neafsey EJ, Noronha A (2004a) Alcohol-induced neurodegeneration: when, where and why? Alcohol Clin Exp Res 28(2):350–364
Crews FT, Nixon K, Wilkie ME (2004b) Exercise reverses ethanol inhibition of neural stem cell proliferation. Alcohol 33(1):63–71
Cui C, Noronha A, Warren KR, Koob GF, Sinha R, Thakkar M, Sullivan EV (2015) Brain pathways to recovery from alcohol dependence. Alcohol 49(5):435–452
Dominguez, G., Belzung, C., Pierard, C., David, V., Henkous, N., Decorte, L.,…Beracochea, D. (2016). Alcohol withdrawal induces long-lasting spatial working memory impairments: relationship with changes in corticosterone response in the prefrontal cortex. Addict Biol. doi:10.1111/adb.12371
Draper, B., Cations, M., White, F., Trollor, J., Loy, C., Brodaty, H.,…Withall, A. (2016). Time to diagnosis in young-onset dementia and its determinants: the INSPIRED study. Int J Geriatr Psychiatry. doi:10.1002/gps.4430
Fabel K, Wolf SA, Ehninger D, Babu H, Leal-Galicia P, Kempermann G (2009) Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. Front Neurosci 3:50
Fontes-Ribeiro CA, Marques E, Pereira FC, Silva AP, Macedo TR (2011) May exercise prevent addiction? Curr Neuropharmacol 9(1):45–48
Gallego X, Cox RJ, Funk E, Foster RA, Ehringer MA (2015) Voluntary exercise decreases ethanol preference and consumption in C57BL/6 adolescent mice: sex differences and hippocampal BDNF expression. Physiol Behav 138:28–36
Gazdzinski S, Durazzo TC, Meyerhoff DJ (2005) Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence. Drug Alcohol Depend 78(3):263–273
Gazdzinski S, Durazzo TC, Mon A, Yeh PH, Meyerhoff DJ (2010) Cerebral white matter recovery in abstinent alcoholics—a multimodality magnetic resonance study. Brain 133(Pt 4):1043–1053
Golub HM, Zhou QG, Zucker H, McMullen MR, Kokiko-Cochran ON, Ro EJ, Suh H (2015) Chronic alcohol exposure is associated with decreased neurogenesis, aberrant integration of newborn neurons, and cognitive dysfunction in female mice. Alcohol Clin Exp Res 39(10):1967–1977
Hamilton GF, Criss KJ, Klintsova AY (2015) Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats. Synapse 69(8):405–415
Hao HN, Parker GC, Zhao J, Barami K, Lyman WD (2003) Differential responses of human neural and hematopoietic stem cells to ethanol exposure. J Hematother Stem Cell Res 12(4):389–399
Harding AJ, Halliday GM, Ng JL, Harper CG, Kril JJ (1996) Loss of vasopressin-immunoreactive neurons in alcoholics is dose-related and time-dependent. Neuroscience 72(3):699–708
Harper C (2009) The neuropathology of alcohol-related brain damage. Alcohol Alcohol 44(2):136–140
Harvey RJ, Skelton-Robinson M, Rossor MN (2003) The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 74(9):1206–1209
Hayes DM, Deeny MA, Shaner CA, Nixon K (2013) Determining the threshold for alcohol-induced brain damage: new evidence with gliosis markers. Alcohol Clin Exp Res 37(3):425–434
He X, Sullivan EV, Stankovic RK, Harper CG, Pfefferbaum A (2007) Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure. Neuropsychopharmacology 32(10):2207–2216
Helfer JL, Goodlett CR, Greenough WT, Klintsova AY (2009) The effects of exercise on adolescent hippocampal neurogenesis in a rat model of binge alcohol exposure during the brain growth spurt. Brain Res 1294:1–11
Kim S, Kim Y, Park SM (2016) Association between alcohol drinking behaviour and cognitive function: results from a nationwide longitudinal study of South Korea. BMJ Open 6(4):e010494
Koob GF (2013) Negative reinforcement in drug addiction: the darkness within. Curr Opin Neurobiol 23(4):559–563
Leasure JL, Nixon K (2010) Exercise neuroprotection in a rat model of binge alcohol consumption. Alcohol Clin Exp Res 34(3):404–414
Llamas-Velasco S, Contador I, Villarejo-Galende A, Lora-Pablos D, Bermejo-Pareja F (2015) Physical activity as protective factor against dementia: a prospective population-based study (NEDICES). J Int Neuropsychol Soc 21(10):861–867
Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (2013) Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis. Neurosci Biobehav Rev 37(8):1622–1644
Majchrowicz E (1975) Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43(3):245–254
Maynard ME, Leasure JL (2013) Exercise enhances hippocampal recovery following binge ethanol exposure. PLoS One 8(9):e76644
McClain JA, Hayes DM, Morris SA, Nixon K (2011) Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics. J Comp Neurol 519(13):2697–2710
McClain JA, Morris SA, Marshall SA, Nixon K (2014) Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence. Addict Biol 19(4):687–699
McMurtray A, Clark DG, Christine D, Mendez MF (2006) Early-onset dementia: frequency and causes compared to late-onset dementia. Dement Geriatr Cogn Disord 21(2):59–64
Meeusen R, Roeykens J, Magnus L, Keizer H, De Meirleir K (1997a) Endurance performance in humans: the effect of a dopamine precursor or a specific serotonin (5-HT2A/2C) antagonist. Int J Sports Med 18(8):571–577
Meeusen R, Smolders I, Sarre S, de Meirleir K, Keizer H, Serneels M, Michotte Y (1997b) Endurance training effects on neurotransmitter release in rat striatum: an in vivo microdialysis study. Acta Physiol Scand 159(4):335–341
Nixon K, Crews FT (2002) Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem 83(5):1087–1093
Nixon K, Kim DH, Potts EN, He J, Crews FT (2008) Distinct cell proliferation events during abstinence after alcohol dependence: microglia proliferation precedes neurogenesis. Neurobiol Dis 31(2):218–229
Nordstrom P, Nordstrom A, Eriksson M, Wahlund LO, Gustafson Y (2013) Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study. JAMA Intern Med 173(17):1612–1618
Obernier JA, White AM, Swartzwelder HS, Crews FT (2002) Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav 72(3):521–532
Pang TY, Renoir T, Du X, Lawrence AJ, Hannan AJ (2013) Depression-related behaviours displayed by female C57BL/6J mice during abstinence from chronic ethanol consumption are rescued by wheel-running. Eur J Neurosci 37(11):1803–1810
Pfefferbaum A, Sullivan EV (2005) Disruption of brain white matter microstructure by excessive intracellular and extracellular fluid in alcoholism: evidence from diffusion tensor imaging. Neuropsychopharmacology 30(2):423–432
Pfefferbaum A, Sullivan EV, Mathalon DH, Shear PK, Rosenbloom MJ, Lim KO (1995) Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clin Exp Res 19(5):1177–1191
Pfefferbaum A, Rosenbloom MJ, Chu W, Sassoon SA, Rohlfing T, Pohl KM, Sullivan EV (2014) White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study. Lancet Psychiatry 1(3):202–212
Radak Z, Hart N, Sarga L, Koltai E, Atalay M, Ohno H, Boldogh I (2010) Exercise plays a preventive role against Alzheimer’s disease. J Alzheimers Dis 20(3):777–783
Rees E, Gowing LR (2013) Supplementary thiamine is still important in alcohol dependence. Alcohol Alcohol 48(1):88–92
Ridley NJ, Draper B, Withall A (2013) Alcohol-related dementia: an update of the evidence. Alzheimers Res Ther 5(1):3
Rosenbloom MJ, Rohlfing T, O’Reilly AW, Sassoon SA, Pfefferbaum A, Sullivan EV (2007) Improvement in memory and static balance with abstinence in alcoholic men and women: selective relations with change in brain structure. Psychiatry Res 155(2):91–102
Sabia S, Elbaz A, Britton A, Bell S, Dugravot A, Shipley M, Singh-Manoux A (2014) Alcohol consumption and cognitive decline in early old age. Neurology 82(4):332–339
Savage LM, Hall JM, Resende LS (2012) Translational rodent models of Korsakoff syndrome reveal the critical neuroanatomical substrates of memory dysfunction and recovery. Neuropsychol Rev 22(2):195–209
Schuch FB, Deslandes AC, Stubbs B, Gosmann NP, Silva CT, Fleck MP (2016) Neurobiological effects of exercise on major depressive disorder: a systematic review. Neurosci Biobehav Rev 61:1–11
Sechi G, Serra A (2007) Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 6(5):442–455
Siette J, Westbrook RF, Cotman C, Sidhu K, Zhu W, Sachdev P, Valenzuela MJ (2013) Age-specific effects of voluntary exercise on memory and the older brain. Biol Psychiatry 73(5):435–442
Sircar R, Sircar D (2005) Adolescent rats exposed to repeated ethanol treatment show lingering behavioral impairments. Alcohol Clin Exp Res 29(8):1402–1410
Slawecki CJ, Thorsell A, Ehlers CL (2004) Long-term neurobehavioral effects of alcohol or nicotine exposure in adolescent animal models. Ann N Y Acad Sci 1021:448–452
Smith MA, Pennock MM, Walker KL, Lang KC (2012) Access to a running wheel decreases cocaine-primed and cue-induced reinstatement in male and female rats. Drug Alcohol Depend 121(1-2):54–61
Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C (2011) Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med 269(1):107–117
Sullivan EV, Pfefferbaum A (2005) Neurocircuitry in alcoholism: a substrate of disruption and repair. Psychopharmacology (Berl) 180(4):583–594
Sullivan EV, Rosenbloom MJ, Lim KO, Pfefferbaum A (2000) Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: relationships to changes in brain structure. Neuropsychology 14(2):178–188
Sullivan EV, Deshmukh A, De Rosa E, Rosenbloom MJ, Pfefferbaum A (2005) Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism. Biol Psychiatry 57(7):768–776
Tateno M, Ukai W, Yamamoto M, Hashimoto E, Ikeda H, Saito T (2005) The effect of ethanol on cell fate determination of neural stem cells. Alcohol Clin Exp Res 29(12 Suppl):225S–229S
Ussher M, Sampuran AK, Doshi R, West R, Drummond DC (2004) Acute effect of a brief bout of exercise on alcohol urges. Addiction 99(12):1542–1547
Vetreno RP, Hall JM, Savage LM (2011) Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment. Neurobiol Learn Mem 96(4):596–608
Withall A (2013) The challenges of service provision in younger-onset dementia. J Am Med Dir Assoc 14(4):230–232
Withall A, Draper B, Seeher K, Brodaty H (2014) The prevalence and causes of younger onset dementia in Eastern Sydney, Australia. Int Psychogeriatr 26(12):1955–1965
Zahr NM, Bell RL, Ringham HN, Sullivan EV, Witzmann FA, Pfefferbaum A (2011a) Ethanol-induced changes in the expression of proteins related to neurotransmission and metabolism in different regions of the rat brain. Pharmacol Biochem Behav 99(3):428–436
Zahr NM, Kaufman KL, Harper CG (2011b) Clinical and pathological features of alcohol-related brain damage. Nat Rev Neurol 7(5):284–294
Zhao YN, Wang F, Fan YX, Ping GF, Yang JY, Wu CF (2013) Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure. Behav Brain Res 236(1):270–282
Acknowledgments
This research was supported by a Society for Mental Health Research Fellowship, followed by a National Health and Medical Research Council/Australian Research Council Fellowship to CJP, and the Victorian State Government Operational Infrastructure Scheme. Many thanks to Professor Andrew J Lawrence for comments on an earlier draft of the manuscript.
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Perry, C.J. Cognitive Decline and Recovery in Alcohol Abuse. J Mol Neurosci 60, 383–389 (2016). https://doi.org/10.1007/s12031-016-0798-4
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DOI: https://doi.org/10.1007/s12031-016-0798-4