Recreational alcohol and brain. GP Study Day 12 th March 2019 Anya Topiwala

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1 Recreational alcohol and brain GP Study Day 12 th March 2019 Anya Topiwala

2 Acute Intoxication Behavioural disinhibition Disrupted socio-emotional processing Impaired psychomotor performance Reduced prefrontal and temporal lobe function

3 Chronic Heavy Consumption and the Brain

4 Wernicke s Encephalopathy opthalmoplegia confusion ataxia THIAMINE

5 Korsakoff s Syndrome Untreated Wernicke s can progress to Korsakoff s Often permanent Thiamine deficiency Prominent anterograde amnesia Prefrontal deficits

6 Chronic heavy consumption Mamillary body atrophy Hippocampal atrophy Frontal atrophy Review - Kril and Halliday 1999

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9 Alcoholic dementia Primary Secondary Prevalence 9-22% Early onset Level? 28u/35u weekly for >5 years* Oslin et al., 1998

10 Recovery on abstinence? 7 days 1 month 7.5 months Durazzo et al., 2014

11 Reduced risk of cognitive decline? Stampfer et al., 2005, NEJM

12 Risk of cognitive decline J shaped curve? Alcohol consumption abstinence moderate heavy

13 Confounding? U. S. Department of Health and Human Services, Substance Abuse and Mental Health Administration. National Household Survey on Drug Abuse, 1997.

14 Brain findings in moderate drinkers

15 Summary Topiwala and Ebmeier 2018

16 Whitehall II Study Sociodemographic and clinical data MRI and neuropsychology Phase Phase 3 Phase 5 Phase 7 Phase 9 Phase 11 Oxford N=10K N=800 N=6K

17 Baby boomers

18 Or.

19 Topiwala et al., BMJ

20 Topiwala et al., BMJ

21 1. Increased alcohol and smaller hippocampi Topiwala et al., 2017

22 Visual hippocampal atrophy Scheltens et al. 1992

23 Scheltens scale normal atrophy Scheltens et al. 1992

24 2. Increased alcohol and smaller hippocampi Weekly units

25 3. Increased alcohol and smaller hippocampi Topiwala et al., 2017

26 Reduced white matter integrity Topiwala et al., 2017

27 Faster cognitive decline Topiwala et al., 2017

28 Putting the pieces together? Topiwala et al., 2017

29 Strengths Duration Prospective alcohol data Large n MRI analysis Phenotyping depth

30 Limitations Observational Generalisable? Self-report alcohol Observer bias? Reverse causation? Underpowered for genetic analysis

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32 Summary Hippocampal atrophy Reduced white matter integrity Faster cognitive decline

33 Clear as mud? Sabia et al., 2018

34 Association between alcohol consumption per week and risk of dementia by age. *Cox regression analysis adjusted for sociodemographic factors. Séverine Sabia et al. BMJ 2018

35 Will we ever get a definitive answer?

36 MACH trial Moderate drinking (5-13 drinks/week) vs. abstinence (<1 drinks/week) Outcomes: MI, ischaemic stroke, hospitalised angina, death Only powered to detect beneficial effect

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38 No association with Alzheimer s disease Susanna C Larsson et al. BMJ 2017;359:bmj.j5375

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40 Tips for primary care Be vigilant for heavy drinking, including middle aged and class men Thiamine Emphasise no clear benefit moderate drinking Young onset memory problems think alcohol Monitor memory in heavy drinkers Probably at least some reversibility, so worth trying to cut down

41 Thiamine benefit Chou et al., 2018: n=5k with thiamine, n=5k without post AUD diagnosis

42 Conclusions

43 Acknowledgements Neurobiology of aging group Funders: UK Medical Research Council Mott scholarship, Linacre College Oxford Alzheimer s Research UK Royal College of Psychiatrists

44 Extent of the exposure Prevalence risky drinking

45 Comparisons of abstainers Sabia et al. Topiwala et al. Mean age (P5) 51.4 (6.1) 53.5 (4.9) Female (%) BMI >30 (%) GHQ score (P5) 3.1 (5.5) 2.8 (4.5) Low SES (%) Less than secondary education (%) 60 30