The Aging Brain & Dementia

1. The Aging Brain & Dementia The Evaluation & Management of Memory Loss Kristin J. Anderson, MD, MPH Swedish Geriatric Fellow 7 June 2011

2. Normal memory changes with aging • Mild Cognitive Impairment • Evaluation of memory loss • Dementia • Definition & Diagnosis • Prevention • Treatment & Management • Patient Care Issues Outline Dementia

3. Old age alone does not cause impairment of cognitive function to the degree which renders the pt dysfunctional • Initial assessment for memory loss should include: H&P, social and functional history, rule out “reversible” dementias • Dementia is a chronic, progressive, and terminal illness • Ativan should not be used for agitation/delirium in geriatric pts • Be mindful of caregiver burnout! Take Home Points Dementia

4. Age-Related Memory Changes

5. Information is stored in 3 parts of memory: • Short-term memory • ie: the name of a person met minutes ago • Recent memory • ie: what was for breakfast • Remote memory • ie: memories of childhood Age-Related Memory Changes

6. Aging may change the way the brain stores information making it harder to remember • Loss of brain cells, total brain mass, and white matter • Decreased “processing speed” • Less ability to form new memories • Short-term and remote memories are not usually affected, but recent memory can be affected • Ex: may forget names of people met recently, this is normal Age-Related Memory Changes

7. Mild Cognitive Impairment

8. Memory problems that can be objectively identified by testing, but NO impairment of overall functioning • Consider onset of abnormalities (acute?), or physical or psychological factors contributing • Some will progress to dementia, others won’t • Still a topic of much research… • Neuropsychological test measures, CSF biomarkers, and neuroimaging studies are being evaluated as predictive tools Mild Cognitive Impairment

9. Warning Signs & Work-Up Memory Loss

10. Memory Loss • Difficulty performing tasks • Problems with language • Disorientation to time and place • Poor Judgment • Difficulty with abstract thinking • Misplacing things • Changes in mood • Changes in personality • Loss of initiative 10 Warning Signs

11. History & physical • Assess for delirium, depression, comorbid conditions (ie sensory impairment) • Corroboration • Functional Status Evaluation & Social History • Cognitive testing • Rule out reversible causes • Neurosyphilis, thyroid disease, B12 deficiency, pseudodementia, HIV, structural lesion • Consider consultation • Geriatrics, neurology, geriatric psychiatry Evaluation of Memory Loss

12. Mini-Cog (clock drawing & 3-item recall) • Folstein Mini-Mental State Exam (MMSE) • Montreal Cognitive Assessment (MoCA) • www.mocatest.org • Animal Naming • Clock drawing test • Formal neuropsych testing Cognitive Testing

13. An Overview of Dementia Dementia

14. Impaired memory, confirmed by testing, & impairment in at least one of the following: • Handling complex tasks • Reasoning • Spatial ability/orientation • Language • Interferes with work, social activities, or relationships • Gradually progressing course • No disturbance in consciousness Dementia: Definition

15. Alzheimer’s disease • Vascular Dementia • Dementia of Parkinson’s disease • Lewy Body Dementia • Frontotemporal dementia • Reversible dementias Types of Dementia

16. Alzheimer’s disease • 60-80% of dementia patients • > 4Million people in the US • 6-8% of persons > 65yo • Nearly 30% > 85yo • Vascular Dementia • 10-20% of dementia patients • No real uniform diagnostic criteria, but features: • Onset of cognitive deficits associated with a stroke • Abrupt onset of sxs followed by stepwise deterioration • Findings on neuro examination c/w prior stroke(s) • Infarcts on cerebral imaging Types of Dementia

17. Dementia with Lewy Bodies • Up to 25% of dementias in some series (may overlap with AD and PD) • Pathologic findings plus: • Detailed visual hallucinations • Parkinsonian signs • Alterations of alertness & attention Types of Dementia

18. Frontotemporal Dementia • Earlier age of onset, mean 57yo, rare after age 75 • Characterized by focal atrophy of the frontal and temporal lobe • Familial occurrence in 20-40% • Reversible Causes of Dementia • Medication-induced • Alcohol-related • Metabolic disorders • Depression (pseudodementia) • Central nervous system neoplasms, chronic subdural hematomas, chronic meningitis • Normal pressure hydrocephalus Types of Dementia

19. Control risk factors for vascular disease • Smoking • Diabetes • HTN and high cholesterol • Keep mind and body active • Stay involved in the community • Gingko biloba? • Insufficient evidence in large trials • Do not give gingko w blood thinners • Vitamin E? • most research does not support use to maintain cognitive performance or slow its decline Preventing Dementia

20. An Overview of Dementia Treatment Dementia Treatment

21. Three basic approaches: • Agents that enhance cognition & function* • Drug treatment for coexisting depression • Treatment of behavioral complications Dementia Treatment Three basic approaches: • Agents that enhance cognition & function* • Drug treatment for coexisting depression • Treatment of behavioral complications • *Poor data, but its what we’ve got… Dementia Treatment “Management of Dementia” Essentials of Clinical Geriatrics, 6th Ed. 2009. pp 165-166.

22. Cholinesterase Inhibitors • Pts with Alzheimer’s Dx have decreased synthesis of acetylcholine and impaired cortical function • Effectiveness best in mild to mod dementia, potential benefit in advanced dementia • May improve cognitive function • May improve or prevent decline in overall function • May delay nursing home admission • Side effects: primarily GI, uncommon may cause symptomatic bradycardia Pharmacologic Treatment of Dementia

23. Cholinesterase Inhibitors • Most studies in pt w Alzheimer’s, some evidence of benefit in vascular dementia, mixed dementia, Lewy body dementia, and Parkinson’s • Recommended to review pt response after 8wks • Four FDA approved medications: • Tacrine(*first approved, not used bec of hepatic toxicity) • Donepezil (Aricept) • Rivastigmine (Exelon) • Galantamine (Razadyne) Pharmacologic Treatment of Dementia

24. Press, Daniel, MD et al. “Cholinesterase Inhibitors in the Treatment of Dementia” uptodate.com. Sept 2010. <30 May 2011>

25. NMDA-Receptor Antagonist: Mematine (Namenda) • Mechanism different than cholinesterase inhibitors, may be neuroprotective • FDA approved for tx of moderate to severe dementia • Fewer side effects than cholinesterase inhibitors • Dizziness most common side effect • Some cases of increased agitation and delusional behavior Pharmacologic Treatment of Dementia

26. Three basic approaches: • Agents that enhance cognition & function • Drug treatment for coexisting depression • Treatment of behavioral complications Dementia Treatment “Management of Dementia” Essentials of Clinical Geriatrics, 6th Ed. 2009. pp 165-166.

27. Diagnosing depression with dementia is complicated • Pts with dementia or depression can not offer insight into their mood or mental ability • Depression alone can produce s/sx of cognitive impairment, called "depressive pseudodementia." • Elderly pts who become depressed are at increased risk of dementia • Treating coexisting depression may provide substantial benefit Treatment of Coexisting Depression

28. Relatively few studies • SSRIs preferred, TCAs can worsen confusion • Studies show efficacy with citalopram & sertraline (Celexa & Zoloft) • In elderly, avoid: • Fluoxetine= long half-life and many drug interactions • Paroxetine = most anticholinergic, can affect cognition • Trazodone can be combined with SSRI for major depression Treatment of Coexisting Depression

29. Three basic approaches: • Agents that enhance cognition & function • Drug treatment for coexisting depression • Treatment of behavioral complications Dementia Treatment “Management of Dementia” Essentials of Clinical Geriatrics, 6th Ed. 2009. pp 165-166.

30. Problematic behaviors occur in 50-80% of dementia patients at some point in their illness • Agitation and Aggression • Psychosis • Sleep Disorders • Sexually Inappropriate Behavior * If behavior disturbance is new, must rule out infection or medication toxicity before initiation of treatment Treating Behavioral Disturbances*

31. Agitation and Aggression • Can be provoked by several mechanisms • Increasing evidence in nonpharmacologic and behavioral methods • Prazosin • Typical and Atypical Antipsychotics • Mixed results regarding SSRIs Treating Behavioral Disturbances

32. More rapid onset than neuroleptics but can worsen confusion and sedation • Studies have found Ativan to be an independent risk factor for delirium • increased risk by 20%!! • Commonly overprescribed for delirium • Limited role for use in drug and alcohol withdrawal Medications: Ativan Francis. “Prevention and Treatment of Delirium and Confusional States” uptodate.com

33. Psychosis • Delusions more common than hallucinations • 30% of pts with severe Alzheimer’s • No tx if pt or caregiver is not bothered • Therapy with antipsychotics if symptoms become problematic • Delusions or hallucinations associated with increased risk for functional/cognitive decline Treating Behavioral Disturbances

34. Sleep Disorders • Common and multifactorial • 25-35% pts • Nonpharmocologictx preferred • May use small doses trazodone • Benzos and antihistamines discouraged • Melatonin and light therapy are safer treatment options but data is not great Treating Behavioral Disturbances

35. Sexually Inappropriate Behavior • Some studies report incidence of 15-25% • Behavioral interventions should be first line treatment • Limited studies on meds- antidepressants, antipsychotics, cholinesterase inhibitors, gabapentin, pindolol, cimetidine and hormonal agents • Antidepressants first drug of choice Treating Behavioral Disturbances

36. Do a thorough social history and needs assessment to prepare for increasing care needs • Designate financial and medical power of attorney • Discuss end-of-life wishes • “Dementia is a terminal disease” • Use community resources • Alzheimer’s Association • Senior Information and Assistance Preparing Families

37. Choices, Attitudes, and Strategies to Care of Advanced Dementia at the End-of-Life (CASCADE) • Prospective cohort of 320 nursing home residents with advanced dementia (+ their families), from 22 NH in the Boston area • Followed for 18mo CASCADE Study Mitchell et al, NEJM Oct 2009.

38. 55% of patients died • PNA, fever, and eating problems were very common, and had high mortality • Dyspnea (46%) and pain (39%) were common • In the last 3 months of life, 40% of pts underwent at least one burdensome intervention • Pts whose DPOA’s understood their prognosis were much less likely to have these interventions (OR = 0.12) CASCADE Study Mitchell et al, NEJM Oct 2009.

39. Understand the clinical course of dementia • Educate patients and their families • Educate the public, and the rest of the health care team • Provide compassionate, patient-centered care What then is our role? Dementia and the PMD

40. Geriatric Assessment Clinic • Alzheimer’s Association • www.alz.org • National Institute on Aging • www.nia.nih.gov/Alzheimers • Senior Information & Assistance • www.seniorservices.org Additional Resources

41. Old age alone does not cause impairment of cognitive function to the degree which renders the pt dysfunctional • Initial assessment for memory loss should include: H&P, social and functional history, rule out “reversible” dementias • Dementia is a chronic, progressive, and terminal illness • Ativan should not be used for agitation/delirium in geriatric pts • Be mindful of caregiver burnout! Take Home Points Dementia

43. References Haymon, Carroll, MD. “Dementia and the Aging Brain” Didactic Presentation, 2010. Kane, Robert et al. “Confusion: Delirium and Dementia”. Essentials of Clinical Geriatrics, 6th Ed. 2009. pp 145-169. Press, Daniel, MD et al. “Cholinesterase Inhibitors in the Treatment of Dementia” uptodate.com. Sept 2010. <30 May 2011> Press, Daniel, MD et al. “Treatment of Dementia” uptodate.com. Feb 2011. <30 May 2011> Press, Daniel, MD et al. “Treatment of behavioral symptoms related to dementia”. www.uptodate.com. Feb 2011 . <27 May 2011> Shadlen et al. “Dementia syndromes” uptodate. Feb 2009. <27 May 2011> “Dietary Supplements Fact Sheet: Vitamin E” NIH Office of Dietary Supplements. http://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional <6 June 2011>