Alzheimer’s Disease and Other Dementia Related Disorders

1. Alzheimer’s Disease and Other Dementia Related Disorders Jason Schillerstrom, MD schillerstr@uthscsa.edu

2. Learning Objectives • List the diagnostic criteria for Major Neurocognitive Disorder. • Describe cognitive deficits across multiple domains • Describe the clinical, pathological, and neuropsychological features associated with Neurocognitive Disorder due to Alzheimer’s disease. • Distinguish between Neurocognitive Disorder due to Alzheimer’s disease, cerebrovascular disease, Lewy Body disease, and frontotemporallobar degeneration.

3. Major Neurocognitive Disorder 1. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains based on: • Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and • A substantial impairment in cognitive performance, preferably documented by standardized testing or, in its absence, another qualified clinical assessment. 2. The cognitive deficits interfere with independence in everyday activities (i.e. at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications). 3. The cognitive deficits do not occur exclusively in the context of a delirium. 4. The cognitive deficits are not better explained by another mental disorder.

4. Major Neurocognitive Disorder Specifywhether due to: • Alzheimer’s disease • frontotemporallobar degeneration • Lewybody disease • vascular disease • traumatic brain injury • substance/medication use • HIV infection, prion disease • Parkinson’s disease • Huntington’s disease • another medical condition

5. Major Neurocognitive Disorder Specify: 1. Without behavioral disturbances 2. With behavioral disturbances: if the cognitive disturbance is accompanied by a clinically significant behavioral disturbance such as psychosis, mood disturbance, agitation, or apathy. Specify: 1. Mild: difficulties limited to instrumental activities of daily living 2. Moderate: difficulties with basic activities of daily living 3. Severe: fully dependent

6. Key Points #1 • The diagnosis of neurocognitive disorders is based on clinical presentation. • There are no “dementia labs”. • There is no dementia imaging study. • Laboratory and imaging are used to “rule out” reversible causes. • There must be clinically significant functional impairment.

7. Cognition – Complex Attention

8. Cognition – Learning and Memory

9. Cognition – Language

10. Cognition – Perceptual Motor

11. Cognition – Social Cognition

12. Cognition – Executive Function

13. Key Point #2 • There are multiple ways to be cognitively impaired. • Executive function is the cognition that is most strongly associated with self-care abilities and decision making capacity.

14. Case Example #1: HPI • 83yr female presents to clinic with her two daughters. • Daughters are concerned: • that their mother repeats her conversations • cannot remember the names of her grandchildren • became confused and disoriented when shopping at a local mall. • The patient’s husband died one year ago and daughters are surprised how much they have to help their mother.

15. Past History • No past psychiatry history. • Only medical issue is hypertension (treated with hydrochlorothiazide) • Retired teacher, 55yr marriage, 2 children • No clinically significant substance use history.

16. Case #1: Neuropsychological Testing Age: 83 years GDS: 2/15 MIS: 6MMSE: 18CLOX1: 7CLOX2: 7EXIT25: 36

17. Alzheimer’s Disease • Insidious onset and gradual progression of impairment in one or more cognitive domains. • Subtypes include ‘early onset’ (65 years of age or below) vs. ‘late onset’ (>65 years of age).

18. Alzheimer’s Association Staging • Stage 1: No impairment • The person does not experience any memory problems. • No evidence of symptoms of dementia. • Stage 2: Very mild cognitive decline • The person may feel as if he or she is having memory lapses — forgetting familiar words or the location of everyday objects. • But no symptoms of dementia can be detected during a medical examination or by friends, family or co-workers.

19. Alzheimer’s Association Staging • Stage 3: Mild Cognitive Decline • Noticeable problems coming up with the right word or name. • Trouble remembering names of new people. • Having noticeably greater difficulty performing tasks in social or work settings. • Forgetting material that one has just read. • Losing or misplacing a valuable object. • Increasing trouble with planning or organizing.

20. Alzheimer’ Association Staging • Stage 4: Moderate Cognitive Decline • Forgetfulness of recent events. • Greater difficulty performing complex tasks, such as planning dinner for guests, paying bills or managing finances. • Forgetfulness about one's own personal history (usually medical). • Becoming moody or withdrawn, especially in socially or mentally challenging situations.

21. Alzheimer’s Association Staging • Stage 5: Moderately severe cognitive decline • Unable to recall their own address or telephone number or the high school or college from which they graduated. • Become confused about where they are or what day it is. • Need help choosing proper clothing for the season or the occasion. • Still remember significant details about themselves and their family. • Still require no assistance with eating or using the toilet.

22. Alzheimer’s Association Staging • Stage 6: Severe cognitive decline • Lose awareness of recent experiences and surroundings. • Difficulty remembering the name of a spouse or caregiver. • Need help dressing properly and may, without supervision, make mistakes such as putting pajamas over daytime clothes or shoes on the wrong feet. • Need help handling details of toileting. • Experience major personality and behavioral changes, including suspiciousness and delusions.

23. Alzheimer’s Association Staging • Stage 7: Very severe cognitive impairment • Lose the ability to respond to their environment and to carry on a conversation. • Need help with much of their daily personal care, including eating or using the toilet. • They may also lose the ability to smile, to sit without support and to hold their heads up. • Reflexes become abnormal. • Muscles grow rigid. • Swallowing impaired.

24. Well Elderly

25. AD Affects Both ECF and Constructions

26. AD Pathology http://www.umsl.edu/~homecare/brain1.PDD.jpg

27. AD Pathology Tangle Plaque

28. FDA Approved Medications • Acetylcholinesterase Inhibitors • donepezil (Aricept) • rivastigmine (Exelon) • galantamine (Razadyne) • tacrine (Cognex) • memantine (Namenda) – NMDA antagonist

29. Summary of FDA Approved Medications • All have demonstrated efficacy by the chosen outcome measures. • However, the effect size is small. • Few patients actually show improvement. • Some outcome measures are less relevant. • Exercise.

30. Case Example #2: HPI • 73yr man presents to clinic with his wife. • She expresses concern for her husband stating, “I think he’s depressed. He just sits in his chair all day doing nothing. I have to do everything.” • He no longer manages finances and he needs assistance with his medications. • He denies feeling depressed and doesn’t understand wife’s concerns.

31. Past History • Takes medication for diabetes, hypertension, and elevated cholesterol. • Had heart catheterization for coronary artery disease 5 years ago. • Retired produce salesman, married to current wife 22 years, 3 adult children. • Smokes one pack per day. Drinks 6-12 beers per week.

32. Case #2: Neuropsychological Testing Age: 73 years GDS: 2/15 MIS: 8MMSE: 26CLOX1: 4CLOX2: 9 EXIT25: 30

33. Vascular Dementia • Evidence for decline is prominent in complex attention and frontal-executive function. • Memory is less impaired relative to loss of executive function. • Focal neurological signs • Evidence of hypertension, valvular heart disease, vascular disease, atrial fibrillation.

34. Vascular Dementia Affects the Executive Control of Clock-drawing

35. Vascular Dementia

36. Vascular Dementia

37. Treatment • Must prevent future stroke / vascular disease: • Aspirin • Anticoagulants • Exercise • Off label treatments for apathy • Antidepressants (sertraline) • Stimulants (methylphenidate)

38. Case #3: HPI • 93yr female is brought to clinic by her daughter (patient lives with daughter). • Daughter reports significant cognitive and functional decline over the past 1-2 years. • The patient reports occasionally seeing little men walking across her mantle. • She was started on antipsychotic by PCP and had severe dystonic reaction. • Daughter also reports that the patient talks and moves excessively in her sleep.

39. Past History • Takes medications for heartburn, urinary incontinence, constipation, hypertension, and atrial fibrillation. • Reports frequent falls (3 in last year). • 12th grade education, housewife, widowed 12 years. • No substance use history.

40. Case #3: Neuropsychological Testing Age: 93 years GDS: 1/15 MIS: 6 MMSE: 22 CLOX1: 5 CLOX2: 7 EXIT25: 24

41. Lewy Body Dementia • Core Features: • Fluctuating cognition with pronounced variations in attention or alertness. • Recurrent visual hallucinations that are well formed and detailed. • Spontaneous features of parkinsonism, with onset subsequent to the development of cognitive decline.

42. Lewy Body Dementia • Suggestive Features • Meets criteria for rapid eye movement (REM) sleep behavior disorder. • Severe neuroleptic (antipsychotic medication) sensitivity.

43. Parkinsonism • Cognitive deficits are more closely associated with rigidity and bradykinesia as opposed to tremor. • Parkinsonism in DLB tends to be: • Less severe than that observed in PD • More symmetric compared to PD • Associated with more gait abnormalities • Less responsive to levodopa (Sinemet)

44. Visual Hallucinations • Fully formed, detailed, 3-dimensional objects, people or animals • Occur in 59%-85% of autopsy confirmed Lewy Body Dementia • Occur in early in the course of the disease (relative to AD hallucinations)

45. Fluctuations • Mimics delirium: waxing and waning of cognition, behaviors, and arousal. • 10% - 80% with poor inter-rater reliability • Differentiating DLB from AD: • Daytime drowsiness • Daytime sleep of 2 hours or more • Staring into space for long periods • Times when the patient’s ideas are disorganized, unclear or illogical • 3 out 4 has a positive predictive value of 83%

46. Other Features • REM Sleep Behavior Disorder: augmented muscle activity and dream content; typically precedes onset of dementia, hallucinations, and Parkinsonism • Autonomic Instability • Perhaps a greater rate of decline • More responsive to acetylcholinesterase inhibitors.

47. Lewy Bodies • Kondi Wong, Armed Forces Institute of Pathology

48. Case Example #4: HPI • APS called to investigate 60yr woman with self-neglect. • Squalor dwelling. No electricity, water, or sewer. • The client had a $2000 past due water bill and a ~$350 past due electrical bill. • APS facilitated a voluntary placement in a supervised setting where the client was allowed to take her dog. However, she became upset with management and decided to leave.  • Would like to renovate home. Plan is to have Channel 4 News do a fundraising story for her.

49. Case Example #4 #1

50. Case #4: Neuropsychological Testing Age: 60 years GDS: 1/15 MIS: 8MMSE: 30CLOX1: 6CLOX2: 13EXIT25: 26