- 1. Approach to the Patient with Dementia Mark Pippenger, MD -
Behavioral Neurology
2. Dementia Dementia is diagnosed when there are cognitive or
behavioral symptoms that: Interfere with the ability to function
Represent a decline from previously higher level of function Are
not caused by delirium or a major psychiatric disorder 3. Delirium
vs. Dementia Features Delirium Dementia Onset Acute Insidious
Course Fluctuating Progressive Duration Days-weeks Months-Years
Consciousness Altered Clear Attention Impaired Normal Reversibility
Usually Rarely Hallucinations Frequent Rare Identifiable Cause
Frequent Rare 4. Evaluation of Dementia Get thorough history,
including history from informant Ask about onset of cognitive
impairment, exact nature of impairment, pace of decline Assess
impact on function Get thorough medical history, family history Get
detailed list of medications, including OTC medications 5.
Evaluation of Dementia Perform general medical and neurological
exam Perform cognitive evaluation 6. Cognitive Batteries MMSE
(Mini-Mental State Exam) SLUMS (St. Louis University Memory Screen)
MoCA (Montreal Cognitive Assessment) 7. Evaluation of Dementia Lab
studies General metabolic labs, thyroid, B12 Imaging CT vs. MRI 8.
Tests Not Routinely Useful for Evaluation of Dementia Syphilis
serology (RPR, VDRL) Homocysteine level Carotid Dopplers or other
vascular imaging EEG PET/SPECT Neuropsychological Testing 9.
Potentially Reversible Causes of Dementia Drugs Depression
Hypothyroidism Normal Pressure Hydrocephalus 10. Drugs that Cause
Dementia Anticholinergic drugs Diphenhydramine, hydroxyzine,
chlorpheniramine, pyrilamine, meclizine, trihexyphenidyl,
benztropine, amitriptyline Opioids Tramadol, hydrocodone, oxycodone
Sedatives generally Benzodiazepines (esp. alprazolam and diazepam),
barbiturates 11. Clues to Dementia Syndrome of Depression Complains
bitterly about memory loss Reported level of cognitive dysfunction
at odds with apparent functional ability Depressed mood, restricted
affect Immediately gives up on cognitive testing, may perform
better when pushed 12. Normal Pressure Hydrocephalus Gait disorder
is invariable Ventricles enlarged out of proportion to generalized
atrophy No test predictive of shunt response Probably pretty rare,
but push to increase diagnosis initiated by shunt manufacturers 13.
Common Causes of Dementia Alzheimer disease (AD) Dementia with Lewy
Bodies (DLB) Vascular Dementia (VaD) Fronto-Temporal Dementia (FTD)
14. Probable Alzheimer Disease Meets criteria for dementia
Insidious onset Evidence of progression Not due to another
condition 15. Presentations of AD Amnestic presentation
Non-amnestic presentations Language presentation Visuospatial
presentation Executive presentation 16. Possible Alzheimer Disease
Atypical course Sudden onset or no evidence of progression
Etiologically mixed presentation Evidence of significant vascular
disease, Lewy body disease, or other medical conditions 17.
Dementia with Lewy Bodies Dementia characterized by
visuoconstructive/executive deficits Core features: Spontaneous
Parkinsonism Spontaneous Visual Hallucinations Prominent
fluctuations 18. DLB vs. PDD Arbitrary one-year rule: If
levodopa-responsive Parkinsonism is present for over one year
before dementia develops, then PDD If Parkinsonism and dementia
develop together, then DLB 19. Vascular Dementia Meets criteria for
dementia Evidence of significant cerebrovascular disease relevant
to dementia: Sudden onset of dementia in temporal association with
stroke Presence of multiple cortical infarcts or severe White
Matter Hyperintensities on imaging 20. Fronto-Temporal Dementia A
group of disorders characterized by selective involvement of
frontal and/or temporal lobes Typically presents before age 65 Does
not respond to any drug treatment 21. Fronto-Temporal Dementia
Three common presentations: Behavioral Variant FTD (bvFTD) Primary
Progressive Aphasia (PPA): Progressive Non-fluent/agrammatical
aphasia Semantic Dementia Logopenic aphasia 22. Behavioral Variant
FTD Odd, alien-like or robotic affect Disinhibited, impulsive
behaviors Stereotyped behaviors Lack of empathy Monotonous voice
Memory may be normal in early stages 23. Summary of Dementia
Etiologies Alzheimer Disease Older, memory loss predominates, neuro
exam normal Dementia with Lewy Bodies Older, Parkinsonism and
Visual Hallucinations Vascular Dementia Sudden onset of dementia
along with a clinical stroke Fronto-Temporal Dementia Younger
patient with behavioral symptoms and odd affect 24. Common Causes
of Dementia 50% 17% 14% 2% 9% 4% 4% AD AD+DLB AD+VaD AD+VaD+DLB DLB
VaD FTD 25. Treatment of Dementia Nonpharmacological Issues
Diagnostic disclosure Addressing patient safety Addressing legal
issues Caregiver support 26. Drugs for Dementia Dementias that may
respond to treatment Alzheimer disease, DLB Dementias with no known
treatments Vascular Dementia*, FTD 27. Drugs for Dementia
Cholinesterase Inhibitors (CEIs) Donepezil (Aricept) Rivastigmine
(Exelon) Galantamine (Razadyne, Reminyl) NMDA Antagonists Memantine
(Namenda) 28. Donepezil (Aricept) 29. ADAS-Cog on Donepezil -2.00
-1.50 -1.00 -0.50 0.00 0.50 1.00 1.50 2.00 0 6 12 18 24 Placebo 5
mg/day 10 mg/day Rogers et al, Neurology 1998;50:136-145 Weeks 30.
Rivastigmine (Exelon) 31. ADAS-Cog on Rivastigmine -5 -4 -3 -2 -1 0
1 2 0 6 12 18 26 Placebo 1-4 mg/day 6-12 mg/day Corey-Bloom et al
1998, Int J Ger Psychopharm 1:55-65 Weeks 32. Galantamine
(Razadyne) 33. ADAS-Cog on Galantamine -2.00 -1.50 -1.00 -0.50 0.00
0.50 1.00 1.50 2.00 0 1 2 3 4 5 Placebo 8 mg/day 16 mg/day 24
mg/day Tariot et al, Neurology 2000;54:2269-2276 Months 34. CEI
Effect Sizes 0.0 1.0 2.0 3.0 4.0 Effect Size on ADAS-Cog Donepezil
Donepezil Rivastigmine Rivastigmine Rivastigmine Patch 9.5
Rivastigmine Patch 17.4 Galantamine Galantamine 35. CEI Adverse
Effects 36. One Month Cost of Drugs 0 75 150 225 300 275 271 131.6
100 7.5 Exelon Patch Namenda 10 mg Rivastigmine 6 mg Galantamine IR
8 mg Donepezil 10 mg 37. Donepezil 23 mg 38. Donepezil 23 mg 0 1 2
2 3 SIB Change 10 mg/day 23 mg/day Farlow et al, Clin Ther 2010,
32(7):1234-1251 39. Donepezil 23 mg Farlow et al, Clin Ther 2010,
32(7):1234-1251 0 19 39 58 77 10 mg/day 23 mg/day 0 weeks 24 weeks
40. Rivastigmine Transdermal 41. Rivastigmine Patch 0 1 2 3
ADAS-Cog Patch 10 Patch 20 Capsule Winblad et al, Neurology
2007;69(Suppl 1):S14-22 42. High-Dose Rivastigmine Patch 43.
High-Dose Rivastigmine Patch -5 -4 -3 -1 0 Week 24 Week 48 9.5 mg
13.3 mg Decline on ADAS-Cog Cummings et al, Dement Geriatr Cogn
Disord 2012;33:341-353 44. Summary on CEIs 45. Memantine (Namenda)
46. Memantine for Mod-Sev AD: Add-On to Donepezil 47. Memantine for
Mod-Sev AD: Add-On to Donepezil 70 73 75 78 80 Placebo + Donepezil
Memantine + Donepezil 0 weeks 24 weeks SIBScore Tariot et al, JAMA
2004; 291:317-324 48. Once-Daily Memantine 49. Once-Daily Memantine
SIBScore Grossberg et al, CNS Drugs 2013; 27:469-478 60 65 70 75 80
0 24 Placebo Memantine 50. Memantine for BPSD 369 patients with
moderate-severe AD with NPI score 13 Randomized to memantine 20
mg/day or placebo, for 24 weeks Primary efficacy measures: SIB, 51.
Memantine for BPSD 0 2 3 5 6 Placebo Memantine NPI Improvement 369
Patients with AD and BPSD Herrmann et al, Int. Psychogeriatr
2013;25:919-927 52. Memantine for Mild AD 53. Memantine for Mild AD
-5 -3 0 3 5 ADAS-Cog CIBIC+ ADCS-ADL NPI Mild Mod Schneider et al,
Arch Neurol 2011; 68:991-998 Drug-Placebo Difference * 54.
Memantine Summary
