Drug induced cognitive impairment Vikas Dhikav, Department of Neurology & PGIMER, GGS IP University, Dr. RML Hospital, New Delhi

Cognition Latin cognitiō, from cognōscere from co- (intensive) + nōscere to learn; see know  mental act or process by which knowledge is acquired, including perception, intuition, and reasoning www.freedictionary.com

Cognitive science

Cognitive impairment T=Thinking R=Remembrance/Reasoning/Reactions to emotions I=Ideas C=Concentration K=knowledge www.australiangov.com/diability

Drug induced cognitive impairment “Drug induced cognitive impairment occurring as a result of drugs is common in elderly and may variably cause or contribute to dementia or MCI” Bradley, Neurology in Clinical Practice, THE DEMENTIAS, chapter 70, vol-2, pp-1855-56, 5th Edition’2008

Contributing drugs A=Anti-cholinergics S=Sedatives H=Hypnotics A=Analgesics Bradley, Neurology in Clinical Practice, THE DEMENTIAS, chapter 70, vol-2, pp-1855-56, 5th Edition’2008

Aims & objectives To know frequency of prescription pattern of drugs capable of producing cognitive impairment in Indian Elderly. To know about average number of drugs elderly patients are taking. To know what is number of patients receiving multivitamins.

Study population Patients attending Memory Clinic of Dr. RML Hospital & PGIMER

Demographic data N=143 Male: female: 110:33 Mean age: 70.1 ± 10.1 Study period: July 2012 to July 2013

Patient distribution (n=143)

Frequency of drug intake (n=143)

Drug distribution (n=60)

Doctor distribution

Zolpidem in present study

Averagye number of drugs per elderly 8.24±3.2

Sex distribution of polypharmacy

Common drugs in polypharmacy

Multivitamins/calcium/vitamin D

Discussion Anand KS & Dhikav V, Ann Indian Acad Neurol 2012

Cholinergic pathways www.brainavm.uhnres.utoronto.ca 

Serotonergic system www.brainavm.uhnres.utoronto.ca 

Norepinephrine pathways www.brainavm.uhnres.utoronto.ca 

Drug list Anti-cholinergic Sedatives Hypnotics Analgesics Anti-depressants Anti-psychotics Anti-epileptics Anti-hypertensives Corticosteroids Anti-cancers Statins Estrogens Moore AR, O'Keeffe ST, Drugs Aging. 1999; 15(1):15-28.

Quantifying drug effect The Anticholinergic Cognitive Burden Scale  He Z, Ball PA. Int Psychogeriatr. 2013;25(9):1425-31.

Mechanism of drug induced cognitive impairment www.frca.uk

Mechanism… www.frca.uk

Mechanism www.natureneuroscience.com

What to look? Prescription drugs Over-the-counter medications Illicit substances Alcohol use Herbs Vitamins Nutraceuticals Homeopathic products Home remedies Drugs of alternative system of medicine Moore AR, O'Keeffe ST, Drugs Aging. 1999; 15(1):15-28.

Is CAM safe? “Patients with Alzheimer’s disease use drugs of alternative & complimentary system of medicine, with or without mainstream medicines” Dhikav V, Anand KS. Int Psychogeriatr. 2012;24(8):1361-2.

Compliance to drugs? “Compliance to drugs potentially capable of slowing down cognitive decline in Dementia is poor” Dhikav, V, Manaklata P, Anand KS. Int Psychoger 2013.

Which age group? “Elderly people are more likely than younger patients to develop cognitive impairment as a result of taking medications” Moore AR, O'Keeffe ST, Drugs Aging. 1999; 15(1):15-28.

Pharmacokinetic changes Increased body fat Less body water Increased volume of distribution Reduced baro-receptor sensitivity Increased number of receptors Reduced metabolic capacity Reduced elimination Goodman & Gillman’s Pharmacological Basis of Therapeutics, 12th Ed, 2012

Increased levels Reduced first pass metabolism Decreased gut metabolism Decreased p-glycoprotein activity (PGP) Decreased albumin levels Goodman & Gillman’s Pharmacological Basis of Therapeutics, 12th Ed, 2012

Metabolic clearance impaired Liver is principal site of metabolism Two phases Phase-I Oxidation (slows in elderly) E.g. dizepam Phase -II Unaffected Goodman & Gillman’s Pharmacological Basis of Therapeutics, 12th Ed, 2012

Elimination impaired Age dependent decrease in glomerular filtration Goodman & Gillman’s Pharmacological Basis of Therapeutics, 12th Ed, 2012

Pharmacodynamic changes Increased number of receptors Higher affinity Post receptor events

Which level? “It is important to note that in the elderly, drug-induced cognitive impairment may occur even in the presence of nontoxic or therapeutic levels of a drug” www.medscape.com

Which type? Delirium is most common type, followed by dementia. Moore AR, O'Keeffe ST, Drugs Aging. 1999; 15(1):15-28.

Frequency? Drug induced delirium=10-30%. Drug induced dementia=2-12%. Moore AR, O'Keeffe ST, Drugs Aging. 1999; 15(1):15-28.

Why delirium & dementia? Impaired cholinergic transmission.

Risk factors? Both dementia & delirium Dementia Delirium Anti-convulsants Dementia Long acting benzodiazepines Delirium Polypharmacy Anticholinergics Psychoactive compounds (e.g. TCADs) Narcotics Moore AR, O'Keeffe ST, Drugs Aging. 1999; 15(1):15-28.

How to avoid? “Start low & go slow” No polypharmacy Special care in people with cognitive impairment Early diagnosis Prompt withdrawal

DREAD anticholinergics? D=Delirium R=Retention of Urine E=Excitement A=Absent sweating D=Dementia

Drugs to be avoided Anti-anxiety Antidepressants Analgesics Maprobamate Antidepressants Amytryptaline Analgesics Indomethacin Anti-histaminics (H1) Diphenhydramine Anti-histaminics (H2) Cimetidine

Avoid… Antipsychotics Long acting benzodiazepines H2 antagonists Thioridazine Long acting benzodiazepines Chlordiazepoxide Diazepam H2 antagonists Muscles relaxants Chlorzoxazone Carisoprodol Methocarbamol Barbiturate Phenobarbitone

Avoid Analgesic Vasodilators Narcotic Oral hypoglycemic Ketorolac Dipyridamol Narcotic Pethidine Oral hypoglycemic Chlorpropamide

Conclusions Drug induced cognitive impairment is common More common in elderly Polytherapy is common Manifestations can be subtle to florid Avoid certain drugs in elderly Promptly discontinue drugs with adverse cognitive effects