1. Louis A. Cancellaro, PHD, MD Professor Emeritus Interim Chair January 11, 2012 Depression in the Presence of Dementia: A Diagnostic Challenge

2. Epidemiology Inexact diagnosis compromises research Major depressive disorder (MDD) either precedes or co-exists with Alzheimer’s Disease (AD) occurs more frequently than can be explained by chance alone Prevalence rates: -MDD in non-demented patients>60yo =0.6-8% -MDD in AD (age/sex matched)=15-30%

3. Epidemiology ≤ 60% of non-demented elderly patients with severe depression are later diagnosed with AD (@ 3 yr. follow-up) Elderly patients with MDD + mild cognitive decline are twice as likely to develop AD than those without mild cognitive decline, who had no greater incidence of AD (@12 yr. follow-up)

4. Etiology of Depression in AD Psychological Grief over loss of cognitive function Biological Analogous to stroke, especially dominant hemisphere, where MDD is prevalent and is responsive to anti-depressants AD has associated deterioration of locus ceruleus, which is purportedly disrupted in MDD, as well

5. Diagnosis Diagnosing depression in elderly Inexact Part of a continuum Sadness ↔ MDD ↔ Psychotic Depression Frequently presents with somatic symptoms as opposed to classical DSM IV criteria

6. Diagnosis Diagnosing depression in elderly Use family + patient for history Report >2 weeks history of (one or more): Loss of energy, loss of interests Increase in somatic symptoms w/o adequate physical explanation Behavioral and/or personality change Suicidal tendencies Delusions

7. Diagnosis Diagnosing depression in elderly No precise diagnostic tests Biochemical Radiological Psychological  Hamilton Depression Rating Scale  DSM-IV Experienced clinicians are the most help

8. Diagnosis Diagnosing AD in elderly with MDD History of cognitive decline beyond just loss of concentrating ability Patient may, or may not, complain of memory loss Cognitive psychological tests Mini-mental status Full battery

9. Diagnosis Diagnosing depression and AD in elderly Even more inexact, especially if signs of AD not previously recognized MDD in elderly frequently presents with personality change and/or somatic symptoms Behavioral change Loss of concentrating ability; poor judgment Vague physical symptoms Loss of energy “Nerves”

10. Diagnosis Depression + AD in elderly Difficult to make a dual diagnosis Serious risks associated with a missed diagnosis Thus, the clinician must consider the coexistence of both conditions if one is present, until proven otherwise

11. Epidemiology Suicide risk: For all patients 65 years of age vs <65: Rate =50% higher Lethality =1 out of 2 attempts vs1 out of 8

12. Diagnosis Depression in elderly with AD Use family + patient for history Report 2 weeks history of (one or more):  Loss of energy, loss of interests  Increase in somatic symptoms w/o adequate physical explanation  Behavioral and/or personality change  Suicidal tendencies  Delusions

13. Dementia and Depression: Distinguishing Features FeatureDementiaDepression OnsetUnclear, insidiousClear, recent, often a major psychotic event ProgressionRelatively steady declineUneven, often no progression Patient insightOften unaware of deficits, not distressed Nearly always aware of deficits and quite distressed AffectBland, some labilityMarked disturbance Test PerformanceGood cooperation and effort, stable achievement, little test anxiety, “near miss” responses Poor cooperation and effort, variable achievement, considerable anxiety, “don’t know” responses Short-term memoryOften impairedSometimes impaired Long-term memoryUnimpaired early in disease Often inexplicably impaired

14. Differential Diagnosis Endocrine Thyroid disease Diabetes Mellitus Cushing’s Addison’s Hyperparathyroidism Cardiovascular and pulmonary disease MI Congestive heart failure COPD

15. Differential Diagnosis Endocrine Cardiovascular and pulmonary disease Anemia B12 Kidney and liver disease Hepatitis C Infections AIDS, TB, hepatitis, chronic fatigue syndrome, other chronic infections

16. Differential Diagnosis Endocrine Cardiovascular and pulmonary disease Anemia Kidney and liver disease Infections Neurological disease CVA, low pressure hydrocephalus, Parkinson’s, subdural hematoma, sleep apnea, brain tumor, seizure disorder

17. Differential Diagnosis Medication side effects and interactions Psychotropics Benzodiazepines Anti-psychotics Anti-convulsants Anti-depressants Sleeping agents Pulmonary and cardiac drugs Steroids

18. Differential Diagnosis Medication side effects and interactions Occult malignancy Lymphomas, leukemias, multiple myeloma Retro-peritoneal tumors Collagen vascular disease SLE, polymyalgia rheumatica, rheumatoid arthritis, scleroderma, fibromyalgia Medications used in treatment Alcoholism Other psychiatric disorders Anxiety disorders Mania

19. Evaluation and Management Suspecting MDD either preceding or coexisting with AD History (from patient and family) Chief Complaint “Depressed” (less common) “Nerves” “Memory loss” Somatic symptoms (↓energy, GI symptoms, weakness)

20. Evaluation and Management History Chief Complaint Course of illness (one or more): 2 weeks ↓interest in daily activities ↓cognitive ability Personality change with impulsiveness Suicidal tendencies

21. Evaluation and Management History Assessment Lack of medical condition sufficient to explain signs and symptoms Patient more detached than usual Meets most of DSM-IV criteria for MDD↓Performance on cognitive tests If AD present, caregivers report ↑frustration, ↑ hopelessness in themselves Suicide risk factors reviewed with patient and family Domestic violence risk factors reviewed Review differential diagnosis, especially medication side effects and interactions

22. Evaluation and Management History Assessment Treatment: MDD in elderly patients with AD Medications Anti-depressants → ≤85% improvement in mood if MDD present Plus occasional improvement in cognition No improvement in mood or cognition if MDD is not present

23. Evaluation and Management History Assessment Treatment: MDD in elderly patients with AD Medications: Anti-depressants: low doses, increase slowly SSRI’s (1/4-1/2 normal starting dose) Fluoxetine (Prozac ® ) Sertraline (Zoloft ®) Paroxetine (Paxil ®) SSRI’s + donepezil (Aricept ® ) = safe SSRI’s + other meds may alter metabolism TCA’s not well tolerated

24. Evaluation and Management History Assessment Treatment: MDD in elderly patients with AD Medications continued Anti-psychotics → ↓ agitation and violent risk ↓ delusions Risperdone (Risperdal ® ) 0.25-1.0 mg/d Haloperidol (Haldol ® ) 0.5-2.0 mg/d Olanzapine (Zyprexa ® ) 2.5-10 mg/d

25. Evaluation and Management History Assessment Treatment: MDD in elderly patients with AD Medications Anti-depressants Anti-psychotics Anti-convulsants Minor tranquilizers → ↓ anxiety ↑ sedation ↓ cognition

26. Evaluation and Management History Assessment Treatment: MDD in elderly patients with AD  Medications  Psychotherapy (slow, repetitive process) Supportive Behavior (statistically significant improvement) Family (especially with caregivers)

27. Evaluation and Management History Assessment Treatment: MDD in elderly patients with AD  Medications  Psychotherapy  Management of suicidal behavior  Frequent assessment  ECT may be required

28. Summary MDD frequently precedes or co-exists with AD Diagnosis of MDD in elderly is inexact If MDD + AD is suspected, effective treatment of the MDD can not only improve the mood and behavior of the patient, but also improve condition

29. I, Louis A. Cancellaro M.D. DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. Disclosure Statement of Financial Interest