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

2. 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

3. Cognitive science

4. Cognitive impairment T=Thinking
R=Remembrance/Reasoning/Reactions to emotions
I=Ideas
C=Concentration
K=knowledge

5. 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 , 5th Edition’2008

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

7. 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.

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

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

10. Patient distribution (n=143)

11. Frequency of drug intake (n=143)

12. Drug distribution (n=60)

13. Doctor distribution

14. Zolpidem in present study

15. Averagye number of drugs per elderly
8.24±3.2

16. Sex distribution of polypharmacy

17. Common drugs in polypharmacy

18. Multivitamins/calcium/vitamin D

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

20. Cholinergic pathways

21. Serotonergic system

22. Norepinephrine pathways

23. 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.

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

25. Mechanism of drug induced cognitive impairment

26. Mechanism…

27. Mechanism

28. 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.

29. 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):

31. 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.

32. 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.

33. 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

34. 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

35. 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

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

37. Pharmacodynamic changes
Increased number of receptors
Higher affinity
Post receptor events

38. 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”

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

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

41. Why delirium & dementia?
Impaired cholinergic transmission.

42. 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.

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

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

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

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

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

48. 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