1. Dementia in Clinical Practice Mary Ann Forciea MD Clinical Prof of Medicine Division of Geriatric Medicine UPHS Photo: Nat Geographic

2. Who has dementia? 78 yr old retired librarian Lives alone, children visit on holidays Family concerned about ‘clutter’ in house, hygiene, unpaid bills 68 yr old child care worker Lives with her husband, drives, in charge of ‘house money’ “Forgot” a child in classroom at end of day

3. Who has dementia (2) ? 84 yr old urology inpatient –Post op day 1: hostile Attempts to strike nurse with cane Refusing blood draw Pulled out catheter 70 yr old homebound patient –Bedbound, mute –Family caregivers –Oral intake decreasing

4. Terms Dementia –Chronic, progressive –Impairment in >1 “domain of cognition” Memory, language use, executive function(judgment), attention, coordination Mild cognitive impairment –Impairment in 1 “domain of cognition” –? “pre-dementia” Delirium –Short term

5. How do we know about Brain Function? Cell structure –Microscope (biopsy, cell culture) –CT, MRI, PET scans Brain regions –imaging “Domains” of cognition –Imaging –Psychological testing

6. Cell structure: Neurons NetworksGrey matter/white matter

7. Brain regions Regions have different activities

8. Domains of cognition Memory Calculation Language Orientation Spatial construction Executive function (judgment)

9. Mapping Memories Natl Geographic

10. What is wrong in dementia? Theories Neurons: waste products, shape of cells, signaling, genetic flaws Regions: biochemistry, structure Domains: communication We don’t yet know.

11. Clinical observations All patients with dementias are not alike. –Age of onset –Family history –Initial symptom –Most troublesome symptom –Rate of progression –Response to treatment Is dementia a symptom, not a disease?

12. Dementia Subtypes Alzheimer’s Disease Fronto-temporal dementia (formerly Pick’s Disease) – 15% Corticobasilar dementias Dementia with Lewy Bodies – 20% –Distinguished from Parkinson’s Disease with dementia Vascular disease

14. Alzheimer’s type dementia Gradual onset Global impairment in cognition –Usually memory impairment predominant Increased risk in siblings –Apo e allele risk Slow progression (5-7 years) –Predictable course (global deterioration scores)

15. AD - pathology Imaging Neuropathology – quantity and location –Senile plaques White matter Amyloid core –Neurofibrillary tangles Tau protein abnormalities –Initial concentrations highest in hippocampus and temporal lobes

16. Plaques

17. Tangle

19. What clinical problems do patients with Alzheimer’s Dementia Encounter? Diagnosis Symptom Management End of life care

20. Case 1 NC 64 yr old retired OR nurse Referred for evaluation of impaired memory –Birthdates, telephone numbers –Impaired job performance for 1-2 yrs prior –Inability to ‘balance checkbook’ Gradual decline over 5 years Died of pneumonia

21. Diagnosis Largely on history Exclude other conditions Role for biomarkers in near future Staging –Mental status testing (MMSE, MOCA, Mini- Cog) –Functional status staging (FAST, GDR)

22. Biomarkers for Alzheimer’s Dementia Apo lipo protein E subtypes –Apo E-2, E-3, E-4 2 copies of E4 increases risk in some populations Spinal fluid ‘tau’ protein levels PET scans for amyloid –People with unexplained MCI –Patients with an unusual course –Early onset dementia

23. Concerns about PET scans How specific is an abnormal test? May not be useful for staging –(how advanced is the disease) Will abnormal scans result in ‘overdiagnosis’ employment or insurance implications?

24. FAST The FAST scale has seven stages: 1 which is normal adult 2 which is normal older adult 3 which is early dementia 4 which is mild dementia 5 which is moderate dementia 6 which is moderately severe dementia 7 which is severe dementia

25. 7a.speaking limited to 6 words or fewer in an average day b. Speech ability limited to the use of a single intelligible word in an average day c. Ambulatory ability lost (cannot walk without personal assistance). d. Ability to sit up without assistance lost (e.g., the individual will fall over if there are no lateral rests [arms] on the chair). e. Loss of the ability to smile.

26. AD - treatment Improve all co-existing conditions! Specific treatments –Cholinesterase inhibitors Donepazil, rivastigmine –Adrenergic stimulants Memantine Treatment of associated symptoms –Agitated behaviors Non pharmacologic, environmental drugs

27. End of life issues Should be anticipated –Advance Directives, conversations with proxies Goals of care –Nutrition –Hospitalization –Caregiver burdens –Hospice involvement

28. Summary “Dementia” is a symptom complex We are in the early stages of understanding the pathology, and discovering effective treatment Optimal care requires advance planning, caregiver involvement, and a team of professionals