2. Mind Cancer: Alzheimer’s Disease and Related Dementias. William D. Rhoades, DO FACP Chair, Department of Medicine Advocate Lutheran General and Chicago Medical School Missoula Medical Conference October 24, 2014 Recognition of stages of dementia, diagnosis and treatment

3. Objectives  Recognize the diagnosis of Alzheimer's disease and related dementias  Discuss the three aspects of dementing illnesses: cognitive losses, functional decline, and behavioral issues  Evaluate treatment modalities for Alzheimer's disease

4. Stages of Cancer  Stage O: Cancer in situ  Stage I: Small cancer not invading deeper tissues or spread to lymph nodes  Stages II and III: Cancers that are larger in size, have grown more deeply into nearby tissues, and have spread to lymph nodes  Stage IV: Advanced or Metastatic cancer spread to other organs or body parts

5. Stage 0: Mild Cognitive Impairment; Dementia in situ

6. Stage O: Mild Cognitive Impairment  DIAGNOSTIC CRITERIA –Isolated memory complaint –Objective memory impairment –Normal general cognitive function –Intact activities of daily living –Not demented

7. MCI: Diverse Clinical Presentations  Amnestic leads to Alzheimer’s Disease  Multiple domains, slightly impaired leads to Vascular Dementia, Alzheimer’s Disease, or questionably due to normal aging  Single non-memory domain leads to Alzheimer’s Disease, Fronto-temporal Dementia, Lewy-Body Disease, Primary Progressive Aphasia, or Parkinson’s Disease

8. MCI: Progression To Alzheimer’s Disease  Annual percentage based on 6 studies reviewed: 6 to 25%  1 study showed 6% annual conversion to AD  1 study showed 25% annual conversion to AD  4 studies showed 12-15% annual conversion to AD  Mayo Clinic study extended to 6 years found 80% of patients converted to AD over 6 years

9. Types of Dementia and Work-up

10. Differential Diagnosis of Dementia 5%10%65%5%7%8% Dementia with Lewy bodies Parkinson’s disease Diffuse Lewy body disease Lewy body variant of AD Vascular dementias and AD Other dementias Frontal lobe dementia Creutzfeldt-Jakob disease Corticobasal degeneration Progressive supranuclear palsy Many others AD and dementia with Lewy bodies Vascular dementias Multi-infarct dementia Binswanger’s disease AD Small GW, et al. JAMA. 1997;278:1363-1371; American Psychiatric Association. Am J Psychiatry. 1997;154(suppl):1-39; Morris JC. Clin Geriatr Med. 1994;10:257-276. 3

11. Dementia workup  Laboratory: CBC, CMP, Vitamin B12 level, and TSH +/- RPR, ESR  Imaging: Some brain imaging is recommended CT without contrast if normal is sufficient, if no imaging done MRI of brain without contrast.  Diagnosis: Transient Alteration of Awareness

12. Mind Cancer: Alzheimer’s Disease

13. BARRIERS TO DIAGNOSIS AND TREATMENT OF AD  By Patients and Families –Patient lacks insight –Fear of diagnosis –Denial of diagnosis –Fear of loss of function –Belief that there is nothing to do –Fear of societal implications i.e. financial, insurance, and embarrassment of a mental illness  By Physicians –Drugs don’t work –Want to be sure of diagnosis before making it because of implications –Early diagnosis difficult without family help –Diagnosis and explanation take time –Suspect diagnosis but no need to make it

14. Stage I: Early Stage Dementia

15. Stage I: Red Flags  Weight loss  Vague complaints  Poor prescription management  Changes in grooming and hygiene  Missed or wrong day appointments  Apathy and/or depression

16. Stage I: Alzheimer’s Disease Screening  Recent events  Orientation to time  Clock drawing test  Three item recall  Animal naming (>12-15 in 1 minute)  Mini-Mental Status Test  Neuropsychological testing

17. Stage I: Early Alzheimer’s disease  Memory impairment  Word finding difficulty  Difficulty with executive function and complex tasks  Geographic disorientation  Reasoning and judgment abilities  Usually remain independent

18. Stage I: Functional losses (independence maintained)  Driving??  Unfamiliar locations may present problems  Maintaining medications, especially if complicated and/or potentially dangerous  Managing higher finances i.e. taxes, large purchases, and financial vulnerability

19. Stage II: Local Spread of Dementia

20. Stage II: Cognition and Cognitive Losses  Memory  Orientation  Executive Function  Language  Visual Spatial Skills

21. Stage II: Functional Losses (living alone)  Instrumental Activities of Daily Living –Shop for yourself –Prepare your own food –Maintain housekeeping –Do laundry –Manage medications –Make telephone calls –Handle finances –Travel on your own

22. Stage III: Spread of Dementia to family members

23. Stage III: Advanced Middle-stage Alzheimer’s disease  Day-night disorientation  Language deterioration  Difficulty with simple chores  Troublesome behavior: –wandering –irritability –paranoia  Depression

24. Stage III: Functional Decline  Inability to maintain Instrumental Activities of Daily Living  Lack of capacity to live safely on your own  Begin to see some erosion of Basic Activities of Daily Living –Assistance with: toileting, eating, dressing, grooming, getting out of bed or chairs, and walking

25. Stage III: Behavioral Issues  Day-night disorientation  Depression  Wandering  Irritability  Paranoia  Hallucinations  Delusions  Agitation

26. Stage IV: Widely Metastatic and End-Stage Dementia

27. Stage IV: Advanced Alzheimer’s disease  Hallucinations  Delusions  Agitation  Erosion of all basic activities of daily living  Total dependence on caregivers  Lack the capacity for basic physical independence

28. Treatment Options for Alzheimer’s Disease

29. Treatment of Stage 0, Stage I, and Stage II disease  Reasonable Expectations of Successful Cholinesterase Inhibitor Therapy –Improve, maintain, or slow decline in ADL and cognitive function –Control troublesome behaviors –Ease loss of independence –Ease caregiver burden –Delay placement in long-term care facility

30. FOUR CHOLINESTERASE INHIBITORS  Cognex (tacrine)  Aricept (donepezil)  Exelon (rivastigmine)  Reminyl (galantamine)

31. Treatment of Stage II and III disease  Memantine (Namenda) –Combination therapy –When to add? –Monotherapy  Behavioral Treatments

32. Stages I,II, III: Nonpharmacologic Therapy Early Alzheimer’s  Use it or lose it  Safety and structure  Memory aids  Alleviating depression Middle-stage AD  Adult day care  Simplify the environment  Redirect behavior  Do not argue

33. Treatment of Stage IV disease Advanced Alzheimer’s disease  Special care units  Structure and activities based on cognition  Additional in-home care assistance  Management of incontinence

34. Stage IV: End-Stage Alzheimer’s Disease  Palliative care  Hospice care  Hospitalizations  Feeding issues including tube feeding  Resuscitation decisions

35. Stage IV: Clinical Management Goals and end-points of therapy:  Social and behavioral therapy  Medications to improve or maintain function and cognition  Medications for certain behaviors  Recognition of delirium and depression  Care of caregivers

36. Who Are the Caregivers?  The overwhelming majority of patients live at home and are cared for by family and friends – 77% are women – 73% are over 50 years of age – 33% are the sole providers – 45% are children of the patient – 49% are spouses – Remainder are close family members or friends

37. Caregiver Burden  Caregivers spend from 40–100 hours per week with the patient  90% are affected emotionally (frustrated, drained)  75% report feeling depressed; 66% have significant depression  Half say they do not have time for themselves and that the stress affects family relations  Many experience a significant loss of income

38. Factors That Create “Breaking Point” for Caregiver  Amount of time spent caring for the patient  Loss of identity  Patient misidentifications and clinical fluctuations  Nocturnal deterioration of patient

39. Conclusions  Dementia and Alzheimer’s disease represent Mind Cancer  Alzheimer’s disease progresses and the stages have different symptoms and treatments  Alzheimer’s disease treatments are beneficial in all three domains: cognition, behavior, and function  Attention to caregiver needs are very important in Alzheimer’s disease