Salim Atrouni , MD Neurologist

1. Dealing With Depression In Alzheimer's Disease SalimAtrouni, MD Neurologist

2. Alois Alzheimer  Auguste – first patient 1906

3. Definition Alzheimer’s Disease is a progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living and a variety of neuropsychiatric symptoms and behavioral disturbances.

4. Epidemiology • 2-3% of people aged 65 show signs of the disease • 25-50% of people aged 85 have symptoms of Alzheimer’s

5. Clinical Features • Gradual development of forgetfulness is the major symptom • Appointment are forgotten and possessions misplaced • Questions are repeated again and again • Remote memories are relatively preserved and recent ones lost

6. Clinical Features Dysphasia • Speech is halting because of failure to recall the needed word • Vocabulary becomes restricted • Comprehension of spoken words seems at first to be preserved • Echolalia

7. Clinical Features Acalculia or Dyscalculia

8. Clinical Features Visuospatial Disorientation • Car cannot be parked • Arms do not find the correct sleeves of the dressing gown • The patient turn in the wrong direction on the way home or becomes lost • The simplest of geometric forms and patterns cannot be copied

9. Clinical Features Ideational and Ideomotor Apraxia • The patient forgets how to use common objects and tools while retaining the necessary motor power and co-ordination for these activities

10. Behavioral changes • Psychosis • Depression

11. Treatment of Alzheimer’ Disease

12. Memantine (EBIXA) • N-methyl-D- aspartate antagonist FDA approved for the treatment of moderate to severe AD • May interfere with glutamatergicexcitotoxicity or may provide symptomatic improvement through effects on the function of hippocampal neurons.

13. Cholinesterase Inhibitors • Approved for the treatment of mild to moderate AD should be considered as a standard of care for patients with AD • Three cholinesterase inhibitors are available: • Donepezil (ARICEPT) • Galantamine (REMINYL). • Rivastigmine (EXELON)

14. Potential Benefits of a Skin Patch • Bypasses the gastrointestinal tract • Not influenced by food intake • Avoids the first-pass effect • Smooth, continuous drug delivery (for continuous efficacy) • Potentially reduced side effects • Improves treatment compliance • Reduces pill burden • Access to optimal doses

15. Components of a Modern Matrix Patch Coloured backing layer Acrylic (drug) matrix Silicone (adhesive) matrix Release liner (peeled off just before patch application)

16. Introducing Exelon Patch

17. Reach Target Dose with Confidence One-step dose increase Exelon 9.5 mg/24 h Patch Exelon 4.6 mg/24 h Patch 4 weeks Starting dose Target dose

18. Exelon Patch: Easy to Apply • Exelon Patch visually reassures that medication is being taken • Exelon Patch can be dosed at any time of day, with or without food • Try to apply Exelon Patch at about the same time every day

19. Exelon Patch can be applied to: Upper or lower back Upper arm Chest Exelon Patch: Flexible and Convenient Lefèvreet al J Clin Pharmacol 2007

20. Symptoms of Depression • Feelings of sadness or unhappiness • Irritability or frustration, even over small matters • Loss of interest or pleasure in normal activities • Reduced sex drive • Insomnia or excessive sleeping • Changes in appetite-depression often causes decreased appetite and weight loss, but in some people it causes increased cravings for food and weight gain • Agitation or restlessness-for example, pacing, hand-wringing or an inability to sit still

21. Symptoms of Depression (Cont’d) • Slowed thinking, speaking or body movements • Indecisiveness, distractibility and decreased concentration • Fatigue, tiredness and loss of energy-even small tasks may seem to require a lot of effort • Feelings of worthlessness or guilt, fixating on past failures or blaming yourself when things aren’t going right • Trouble thinking, concentrating, making decisions and remembering things • Frequent thoughts of death, dying or suicide • Crying spells for no apparent reason • Unexplained physical problems, such as back pain or headaches

22. Depression in Alzheimer’s Disease • Depression occurs in about 20 to 40 percent of people with Alzheimer’s disease • Early Alzheimer’s and depression share many symptoms, so it can be difficult to distinguish between the two disorders

23. Depression in Alzheimer’s Disease (Cont’d) • One important difference between Alzheimer’s and Depression is the effectiveness of treatment. Alzheimer’s drugs can only slow the progression of cognitive decline, but medications to treat depression can improve a person’s quality of life dramatically • People who have both Alzheimer’s and Depression may find it easier to cope with the changes caused by Alzheimer’s when they feel less depressed

24. Features of Depression in Alzheimer’s Disease • Dementia itself can lead to certain symptoms commonly associated with depression, including apathy, loss of interest in activities and hobbies, and social withdrawal and isolation • The cognitive impairment in Alzheimer’s patients makes it difficult for them to articulate their sadness, hopelessness, guilt and other feeling associated with depression • Depression in Alzheimer’s is often similar in its severity and duration to the disorder in people without dementia

25. Features of Depression in Alzheimer’s Disease(Cont’d) • In some cases it may be less severe, not last as long, or not recur as often • Depressive symptoms may come and go, in contrast to memory that worsen steadily overtime • People with Alzheimer’s and depression may be less likely to talk openly about wanting to kill themselves and they are less likely to attempt suicide than depressed individuals without dementia • Frequency of depression in men and women with Alzheimer’s is equal

26. Diagnosis of Depression in Alzheimer’s Disease • Side effects of medications or an unrecognized medical condition can sometimes produce symptoms of depression • Evaluation will include a review of the medical history, a physical and mental examination and interviews with family members who know the person well

27. Assessment of Depression in Dementia • Mood: • Does the patient say that they feel depressed or unhappy ? • Do they look depressed or cry frequently? • Is there diurnal variation in mood (worse in the morning)? • Does the patient still enjoy the things they used to enjoy (a sing-song; visit of grandchildren)?

28. Assessment of Depression in Dementia (Cont’d) • Speech: • Has speech reduced in rate or volume? • If the patient normally signs or hums do they still do so? • Activity: • Has activity declined, does the patient seem to lack energy? • Is the patient overactive; do they wring their hands similarly? • Does activity change during the day; is the patient worse in the morning?

29. Assessment of Depression in Dementia (Cont’d) • Sleep: • Has the pattern of sleep changed? • Is there a regular disturbance of night-time sleeping; if so is it early morning waking? • Appetite: • Has appetite changed; is there weight loss?

30. Diagnostic Criteria for Depression of Alzheimer’s Disease In addition to an Alzheimer diagnosis, the patient must have a change in functioning characterized by three or more of the following symptoms during the same two-week period. The symptoms must include at least one of the first two on the list : • Significantly depressed mood-sad, hopeless, discouraged, tearful • Decreased positive feelings or reduced pleasure in response to social contacts and usual activities • Social isolation or withdrawal • Disruption in sleep • Agitation or slowed behavior • Irritability • Fatigue or loss of energy • Feelings of worthlessness or hopelessness, or inappropriate or excessive guilt • Recurrent thoughts of death, suicide plans, or suicide attempt.

31. The Effects of Depression in Alzheimer’s Disease • Depression results in a poor quality of life in AD • Depressive patients will function at a level below their ability as a consequence of reduced energy and motivation and require increasing support • Depression is one factor leading to aggression • Carers find that the behavioral disturbance and psychiatric problems are far harder to cope with than the disease itself • Carers of depressed AD patients are themselves more depressed and anxious than carers of patients without depression

32. Treating Depression in Alzheimer’s Disease Combination of medicine, support and gradual reconnection of the person to activities and people he or she finds pleasurable.

33. Non-Drug Approaches • Schedule a predictable daily routine, taking advantage of the person’s best time of day to undertake difficult tasks, such as bathing • Make a list of activities, people or places that the person enjoys now and schedule these things more frequently • Help the person exercise regularly, particularly in the morning

34. Non-Drug Approaches (Cont’d) • Acknowledge the person’s frustration or sadness, while continuing to express hope that he or she will feel better soon • Celebrate small successes and occasions • Find ways that the person can contribute to family life and be sure to recognize his or her contributions • At the same time, provide reassurance that the person is loyed, respected and appreciated as part of the family, and not just for what she or he can do now

35. Non-Drug Approaches (Cont’d) • Nurture the person with offers of favorite foods or soothing or inspirational activities • Reassure the person that he or she will not be abandoned • Consider supportive psychotherapy and/or support group

36. Pharmaceutical Approaches Antidepressants are prescribed for depressive symptoms • The most commonly used: • Escitalopram • Sertraline • Fluoxetine • Paroxetine • Venlafaxine • Mirtazapine

39. Thank you