Dementia Prevention And Substance Use Disorders

Dementia from Addictive Compounds

As a geriatric psychiatrist and an addiction psychiatrist, what I see happening in both professional literature and lay literature is mind boggling.  There is a clear bias advocating for the benign and even therapeutic effects of alcohol and addicting drugs.  What most articles omit is that the health effects of alcohol are limited to no more than two standard drinks per day for men and one drink per day for women.  The drinks cannot be all taken on the same day.  The limits are per day not per week.  Most of the evidence also suggests that the alcoholic beverage should be wine rather than beer or distilled spirits.  Recent studies suggest that of the 70% of Americans who drink - about 1/3 of them are probably drinking in excess of those amounts.  Doing the arithmetic that amounts to about 56 million people.  Even a low percentage of brain injury will result in a significant number of cases od dementia. Moderate to heavy drinking (3-12+ drinks/day) carries the associated risks of high carbohydrate intake and sedentary life style.  It is very common to find that moderate to heavy drinkers stop their usual outdoor activities and exercise and spend a lot of time watching television.  This can lead to obesity, glucose intolerance and dyslipidemia and in the worst case scenario metabolic syndrome.  All of those consequences lead to increased risk of cardiovascular and cerebrovascular disease.  

There are addiction risks with alcohol consumption apart from atherosclerotic heart disease. Alcohol is proarrhythmic and doubles the risk for arrhythmia.  In one large Danish study (11) they noted that alcohol intake and a history of atrial fibrillation was a risk factor for ventricular fibrillation.  Some authors view alcohol use a risk factor in preventable atrial fibrillation.  In clinical practice it is very common to interview patients with atrial fibrillation who notice that during times of heavy alcohol use they can sense that they are in atrial fibrillation and they spontaneously convert to sinus rhythm as their blood alcohol levels drop.  Atrial fibrillation is a causative mechanism for embolic stroke and associated cognitive disorders.

The direct toxic effect of alcohol on the brain has been debated for years. Amnesia from Wernicke-Korsakoff syndrome is a known diagnostic entity related to thiamine deficiency associated with excessive alcohol use.  It is probably underdiagnosed in most populations compared with postmortem diagnoses of the specific lesions consistent with Wernicke-Korsakoff syndrome (WKS).  A large number of people with alcohol use problems have demonstrable cognitive effects on testing as well as structural and functional brain imaging brain imaging studies suggest some effect on brain structure.  The lack of a pathological lesion has led some to suggest that this is a non-specific effect, but it is very likely that there are several variants of cognitive dysfunction related to alcohol use that are not associated with WKS (12).  On a clinical basis it is very common to see patients with subjective cognitive impairment that typically involves working memory, declarative memory, and executive function.  In treatment setting where abstinence from alcohol is assured many of these problems seem to clear up after about 60 days of abstinence.  But there are also populations of people with varying degrees of anterograde and retrograde amnesia that is not as dense as expected with full WKS.  Many of these patients are seen in treatment settings and never referred for comprehensive assessments of their cognitive disorder.  To my knowledge there have been no studies looking at the issue of whether or not partial amnestic states correlate with WKS lesions at autopsy.        

The problems with recognizing and treating cognitive disorders associated with substance use problems are exemplified in the first few paragraphs about alcohol.  They are no less important for other commonly abused substances.  In the case of stimulants, amphetamine analogues are known neurotoxins.  Studies by Volkow and others have shown persistent changes in dopaminergic neurons up to 15 months after the last use.  This may correlate with a persistent attentional deficit that leads patients to conclude that they now have attention deficit disorder.  Additional brain insults from hemorrhagic strokes and cardiovascular problems associated with long term stimulant use are common.  Stimulants are well known precipitants of acute myocardial ischemia and brain complications from hypoperfusion and emboli.  Acute hypertension and tachycardia are part of the acute intoxication syndrome that can lead to hypertension and hemorrhagic stroke.  This recurrent cycle leads to commonly observed complications of cardiomyopathy in the 4th and 5th decades of life and heightened risk of ventricular arrhythmias and cardiac arrest.

The graphic at that top of this post is not exhaustive - but point out some significant acute and chronic complications of drug use that can lead to permanent brain injury.  These mechanisms cannot be overlooked as avoidable causes of dementia.  I will be trying to elaborate on this graphic in the future to look at developing a review in this area.  Any acute acre and addiction psychiatrist is probably more aware of these syndromes and complications because they are encountered in clinical practice.  I have not seen any formal estimates of the fraction of dementia cases are preventable by avoiding these compounds.  The largest fraction of dementia cases would likely be attributable to the most commonly used drugs - tobacco and alcohol.  Drugs that kill more people acutely on a proportional basis like stimulants and opioids probably leave fewer survivors with dementia as a complication.  

Contrary to the conventional wisdom these days - avoiding dementia is another strong argument for a sober life style.


George Dawson, MD, DFAPA


References:

1: de Gaetano G, Costanzo S, Di Castelnuovo A, Badimon L, Bejko D, Alkerwi A,Chiva-Blanch G, Estruch R, La Vecchia C, Panico S, Pounis G, Sofi F, Stranges S, Trevisan M, Ursini F, Cerletti C, Donati MB, Iacoviello L. Effects of moderate beer consumption on health and disease: A consensus document. Nutr Metab Cardiovasc Dis. 2016 Jun;26(6):443-67. doi: 10.1016/j.numecd.2016.03.007. Epub 2016 Mar 31. Review. PubMed PMID: 27118108.

Moderate consumption is defined as 1 drink per day in women and 2 drinks per day  for men in a non-binge drinking pattern. J-shaped dose-response curve

2: Fernández-Solà J. Cardiovascular risks and benefits of moderate and heavy alcohol consumption. Nat Rev Cardiol. 2015 Oct;12(10):576-87. doi: 10.1038/nrcardio.2015.91. Epub 2015 Jun 23. Review. PubMed PMID: 26099843.

U-Shaped dose-response curve

3: Matsumoto C, Miedema MD, Ofman P, Gaziano JM, Sesso HD. An expanding knowledge of the mechanisms and effects of alcohol consumption on cardiovascular disease. J Cardiopulm Rehabil Prev. 2014 May-Jun;34(3):159-71. doi: 10.1097/HCR.0000000000000042. Review. PubMed PMID: 24667667.

4: Graff-Iversen S, Jansen MD, Hoff DA, Høiseth G, Knudsen GP, Magnus P, Mørland J, Normann PT, Næss OE, Tambs K. Divergent associations of drinking frequency and binge consumption of alcohol with mortality within the same cohort. J Epidemiol Community Health. 2013 Apr;67(4):350-7. doi: 10.1136/jech-2012-201564. Epub 2012 Dec 12. PubMed PMID: 23235547.

5: Weyerer S, Schäufele M, Wiese B, Maier W, Tebarth F, van den Bussche H,Pentzek M, Bickel H, Luppa M, Riedel-Heller SG; German AgeCoDe Study group (German Study on Ageing, Cognition and Dementia in Primary Care Patients). Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older. Age Ageing. 2011 Jul;40(4):456-63. doi: 10.1093/ageing/afr007. Epub 2011 Mar 2. PubMed PMID: 21367764.

6: Bathla M, Singh M, Anjum S, Kulhara P, Jangli S IIIrd. Metabolic syndrome indrug naïve patients with substance use disorder. Diabetes Metab Syndr. 2016 Sep 3. pii: S1871-4021(16)30183-7. doi: 10.1016/j.dsx.2016.08.022. [Epub ahead of print] PubMed PMID: 27618517

Alcohol was the main substance used by patients meeting WHO criteria for Metabolic Syndrome.

7: Vancampfort D, Hallgren M, Mugisha J, De Hert M, Probst M, Monsieur D, Stubbs B. The Prevalence of Metabolic Syndrome in Alcohol Use Disorders: A Systematic Review and Meta-analysis. Alcohol Alcohol. 2016 Sep;51(5):515-21. doi: 10.1093/alcalc/agw040. Epub 2016 Jun 23. Review. PubMed PMID: 27337988. 

1 person in 5 with alcohol use disorder has metabolic syndrome.

8: Wakabayashi I. Frequency of heavy alcohol drinking and risk of metabolicsyndrome in middle-aged men. Alcohol Clin Exp Res. 2014 Jun;38(6):1689-96. doi: 10.1111/acer.12425. Epub 2014 May 12. PubMed PMID: 24818654.

Positive correlation between heavy drinking and metabolic syndrome.

9: Yousefzadeh G, Shokoohi M, Najafipour H, Eslami M, Salehi F. Association between opium use and metabolic syndrome among an urban population in Southern Iran: Results of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS). ARYA Atheroscler. 2015 Jan;11(1):14-20. PubMed PMID: 26089926; PubMed Central PMCID: PMC4460348.

Current opioid users had the highest prevalence of metabolic syndrome (39.6%) but the study was confounded by a high baseline rate in the controls (37.2%).

10:   Brunner S, Herbel R, Drobesch C, Peters A, Massberg S, Kääb S, Sinner MF.Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich Octoberfest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW). Eur Heart J. 2017 Apr 25. doi: 10.1093/eurheartj/ehx156. [Epub ahead of print] PubMed PMID: 28449090.

11: Jabbari R. Ventricular fibrillation and sudden cardiac death during myocardialinfarction. Dan Med J. 2016 May;63(5). pii: B5246. Review. PubMed PMID: 2712702.

12: Ridley NJ, Draper B, Withall A. Alcohol-related dementia: an update of the evidence. Alzheimers Res Ther. 2013 Jan 25;5(1):3. doi: 10.1186/alzrt157. eCollection 2013. Review. PubMed PMID: 23347747.


Supplementary:

The calculation for the following observation:

Recent studies suggest that of the 70% of Americans who drink - about 1/3 of them are probably drinking in excess of those amounts.  Doing the arithmetic that amounts to about 56 million people.

321M(current US population) - 80M (population less than drinking age) x 0.7 (percentage of population that drinks) x 0.3 percentage of excess drinkers = 56 million people.

 

Delirium Reinvented

One of my colleagues posted an article from the The Atlantic on delirium to her Facebook feed a few days ago.  Most of my colleagues in that venue are hospital, consultation-liaison, addiction or geriatric psychiatrists and we diagnose a lot of delirium.  Entitled the Overlooked Danger of Delirium in Hospitals it makes it seem like this is some kind of new and strange diagnostic category.  The article talks about the prevalence, the association with critical illness and advanced age, and the diagnostic overlap of dementia and delirium.  We hear from an Internal Medicine specialist Sharon Inouye, MD about the need to correctly diagnose and prevent delirium.  She mentions that as opposed to a decade ago, physician and nurses are all taught about delirium.  There is mention of the CAM (Confusion Assessment Method) that Inouye developed.  Like all health care articles there are estimates of the massive cost of delirium as well some prevention techniques.  There is also political concern that Medicare will declare delirium a "never" event with penalties for any hospital with cases of delirium.  That would be unfortunate because it makes a mistake that also seems to be made in this article - that delirium is a manifestation of many illnesses, especially the kind of illnesses that patient's are hospitalized for.

The article seemed odd to me because it was written from the perspective that delirium is an iatrogenic preventable event!  Certainly that can be the case. Delirium is a primary feature of hundreds of different disorders and recognizing delirium and those etiologies is potentially life saving.  Delirium can mimic psychiatric conditions due to the presence of hallucinations and delusional thinking.  For example, it is entirely possible to see a patient in the emergency department with apparent paranoid delusions and miss the fact that they happen to be delirious.  Sometimes the only sign is that the patient is inattentive and when vital signs are checked they have an elevated temperature.  This can be a common presentation of viral encephalitis in younger patients or urinary tract infections in the elderly.  It is bad form to miss either of those diagnoses and attribute the symptoms to a psychiatric disorder.  Another common form of delirium that is missed is drug or alcohol intoxication or withdrawal states.  Some intoxicants will render the patient totally unable to care for themselves until they are detoxified.  Other deliriums from alcohol or sedative withdrawal are life threatening and can be associated with seizures and other life-threatening states.  An acute change in a person's mental state resulting in delirium needs to be recognized and assessed as a medical emergency.    

One of the first cases of delirium that I ran into after residency was a case of cerebral edema that I was consulted on because of "hysterical behavior".  After that, I worked in and eventually ran a Geriatric Psychiatry and Memory Disorders Clinic for about 8 years.  The majority of people coming to that clinic had dementia of some sort.  They would see me and a neurologist.  We started out with an internist who was also a geriatric specialist, but that turned out to be overkill in terms of the number of medical specialists seeing each person in an outpatient clinic.  We eventually opted for records from the patient's primary care physician.  One of the most valuable functions of that clinic was our ability to follow people with prolonged deliriums.  Once a delirium has been established by a disease state and that state has resolved the delirium can persist for months.  Some of the outliers in that clinic took up to 6 months to clear.  We found that in many cases, the patients were extensively tested for intellectual ability and functional capacity when they were in the delirious state and told that they had dementia.  It was always instructive for the patient and family to get the testing repeated when we were sure the delirium had resolved and find that they had been restored to baseline.  Many people know their full scale IQ score and were relieved to see that they were back to that level of functioning.

A valuable lesson from working in that clinic and in hospital settings was the use of the electroencephalogram (EEG) as a possible test for delirium.   EEGs are commonly viewed as diagnostic tools to determine if a person is having seizures, but they also contain a lot of information about brain metabolism.  EEGs can be difficult to interpret especially if the patient is on a number of medications that affects cerebral metabolism. There are two broad categories of EEG patterns for delirium: one with a predominance of slow frequencies (designated theta and delta) and one with faster frequencies (designated beta).  We found a number of people with very significant cognitive impairment that was thought to be either a psychiatric disorder or a dementia but with a profound degree of slowing more consistent with a delirium.    

Delirium is an augenblick diagnosis for most psychiatrists.  The patient could appear disinterested, apathetic, agitated, or overtly confused.  It occurs in situations where brain physiology is compromised such as post surgical/anaesthesia states, drug intoxication states, drug reaction states, or possible physical illness delirium should be high on the differential diagnosis.  The Atlantic article makes it seem like knowledge about delirium is something very recent, but psychiatrists have been focused on it for a long time.  In the first two iterations of the DSM, delirium was subsumed under the categories of acute and chronic brain syndromes (DSM-I 1952) and organic brain syndromes (DSM-II 1968).  The current diagnostic code and name has been with us since the DSM III in 1980.  One of the early experts in delirium was Zbigniew J. Lipowski, MD, FRCP(C) - a Professor of Psychiatry from the University of Toronto.  His first text on the condition was Delirium: Acute Brain Failure in Man published in 1980.  That was followed by his classic text,  Delirium: Acute Confusional States published in 1990.  A comparable text from a neurological standpoint was Arieff and Griggs Metabolic Brain Dysfunction in Systemic Disorders published in 1992.

Any psychiatrist trained in the past 30 years should be able to diagnose delirium and come up with a differential diagnosis and monitoring or treatment plan.  A significant number of people can be followed on an outpatient basis as long as they are in a safe environment with the appropriate level of assistance.  The main goal of treatment is to make sure that the primary medical illness that led to the problem has been treated.  There are no known medications that will accelerate the resolution of these symptoms and medical management usually involves getting rid of medications that can lead to cognitive problems.  That can include benzodiazepines, antidepressants and antipsychotics but also more common medications like antihistamines and anticholinergic medications that are used for various purposes.  Like most psychiatric interventions in our health care system, clinics with staff interested in doing this work are few and far between generally because they are rationed resources.

There is a current movement underway to train Family Physicians and Internists (like Dr. Inouye) to recognize and prevent delirium.  In the minority of hospitals where psychiatrists work they are also a clear resource.  A delirium in a previously healthy person should signal a fairly comprehensive evaluation to figure out what happened.

And whenever there is a question of whether a person has a delirium or a psychiatric disorder - call a psychiatrist.  Psychiatrists know a lot about delirium and have for decades.



George Dawson, MD, DFAPA



Reference:

Sandra G. Boodman.  Overlooked Danger of Delirium in Hospitals.  The Atlantic.  June 7, 2015.


Supplementary 1:  The graphic is a standard EEG.  I tried to post a slowed EEG seen in delirium, but the publisher wanted what I consider to be an exorbitant fee for a non-commercial blog.  If anyone has a slow anonymous EEG laying around, send me a copy and I will post it.