The Top 10 Things a Family Physician Needs to Know About Dementia Care

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The Top 10 Things a Family Physician Needs to
Know About Dementia Care

• William M. Simpson, Jr., MD
• Professor of Family Medicine
• Medical University of South Carolina
• simpsowm_at_musc.edu//843-792-3607

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1. All dementia isnt
Alzheimers type dementia, but most of it is.
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Alzheimers Disease Overview

• Progressive, degenerative brain disease
  characterized by increasing loss of memory and
  other cognitive functions
• Changes in behavior, personality, judgment, and
  ADLs
• Most common cause of dementia among people age 65
  or over

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Alzheimers disease progression

• Usually from temporal lobes--memory, aphasia,
  anomia
• To parietal lobes--disorientation in space,
  acalculia, R-L discrimination, asteriognosis,
  agraphesthesia
• To frontal lobes--apraxia,agnosia, difficulties
  with abstraction/logical reasoning, personality
  changes

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Dementia with Lewy Bodies

• Fluctuating course, rapidly progressive
• Hallucinations--detailed and prominent
• Psychosis, delusional or paranoid ideation
• Mild extrapyramidal signs
• Cortical deficits--4As(amnesia, anomia, agnosia,
  apraxia)
• Subcortical deficits--attention, verbal fluency

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Vascular Dementia

• Does not follow predictable, progressive course
• Pure vascular dementia probably lt5 of cases
• Abrupt onset usually following CVA or series of
  CVAs
• Focal neurologic findings
• Fluctuating cognitive impairment

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2. Major authorities do not recommend screening
for dementia in the elderly, but there are times
when you should
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Importance of Early Diagnosis

• Permits early treatment of reversible dementias
  or symptoms of AD
• Reduces use of healthcare resources, especially
  ineffective use
• Gives patient and family an explanation for
  symptoms and allows planning for future
• Allows identification of and compensation for
  unsafe behaviors

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Differential Diagnosis

• Vascular dementias
• Parkinsons disease
• Dementia w/Lewy bodies
• Picks disease
• Huntingtons disease
• Normal pressure hydrocephalus

• Major Depression
• Metabolic disorders, including B12 deficiency,
  drug intox, hypothyroidism, ETOH
• Infectious causes, including HIV, neurosyphilis

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3. Screen for dementia when the patient is
concerned, when the family is concerned, or when
you are concerned that it is present
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4. Look for contributors to decreased mental
acuity---drugs, other diseases, inactivity.
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5. If the diagnosis of Alzheimers type dementia
is made, eliminate contributors, if possible, and
give trial of AChEI
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Reported Advantages of newer Acetylcholiesterase
Inhibitors

• Fewer side effects
• Delay progression for 2 years or more
• Delay institutionalization for similar period
• Effective even in nursing home population to
  delay late stage vegetation

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Currently Available Acetylcholinesterase
Inhibitors

• Donepezil
• Rivastigmine
• Galantamine

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Donepezil (Aricept)

• Once daily HS dosing
• Starting dose 5 mg
• Increase to 10 mg after 4-6 weeks
• Common side effects GI symptoms
• No hepatic effects, no monitoring
• No significant drug-drug interactions

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Rivastigmine(Exelon)

• 1.5mg BID initial dose
• Increase by 1.5mg BID q2weeks to max of 6mg BID
• If treatment interrupted gtseveral days, restart
  at lowest dose and re-titrate as above

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Rivastigmine (Exelon)

• Effects butylcholinesterase in addition to
  acetylcholinesterase
• Whether this has any specific benefit in AD is
  unknown
• Taken with food
• No LAE monitoring, no significant drug-drug
  interactions

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Galantamine(Reminyl)

• Initial dose 4mg BID
• Increase by 4mg BID at 4 week intervals to max
  12mg BID
• Re-titrate if therapy interrupted
• Not recommended in severe hepatic or renal
  impairment
• CYP3A4, 2D6 inhibitors increase bioavailability

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Galantamine (Reminyl)

• Effects nicotine receptors, but not
  butylcholinesterase receptors, unknown clinical
  effect
• Best taken with food

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AChEI Adverse Events

• GI upset, fatigue, anorexia
• May aggravate asthma, COPD, bladder outlet
  obstruction

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REMINDER

• A years supply of an acetylcholinesterase
  inhibitor(AChE-I) is less than a months cost of
  a modest nursing home---and may delay the need
  for 1-2 years
• Families have little to lose with a three month
  or longer trial of an AChE-I

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NMDA-receptor antagonists

• N-methy D-aspartate
• Beta amyloid disrupts transmission of
  glutamate(important in learning and memory)
• NMDA-receptor antagonists prevent glutamatergic
  overstimulation which can be toxic to neurons

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Memantine HCl--Namenda

• Available in Germany since 1982
• Approved for US use in patients with moderate to
  severe AD in 2003
• Begin with 5mg qD, increase weekly by 5mg to 10mg
  BID (titration pack available)

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Comparative Studies

• Donepezil/galantamine-12 week--more tolerated and
  remained on max dose of donepezil, greater
  improvement ADLs
• 7th Int.Geneva/Springfield Symp. On Advances in
  AD 2002
• Donepezil/reminyl-12 week--donepazil better
  tolerated, similar cognitive improvements
• Int J Clin Prac 200256(6)441-6

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More Comparative Studies

• 52-week study 76 galantamine and 67 aricept
  patients, ADLs maintained equally, cognition
  same or improved in 58 with galantamine, 30
  with aricept (plt.001).
• Wilcock G, Howe I, Coles H, et al. A longterm
  comparison of galantamine and donepezil in the
  treatment of Alzheimers disease. Drugs Aging
  200320777-789

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Memantine

• Pts. On memantine showed greater cognitive
  function and overall performance, improvements
  continued in 6 month open label continuation
  phase
• Neurobiol Aging. 200223(Suppl 1)S555
• Severe dementia--73 improved function
• Int J Geriatr Psychiatry. 199914135-46

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Memantine

• It has been modestly effective in some US
  studies in improving performance in patients with
  moderate-to-severe Alzheimers disease. There is
  no evidence that memantine has any effect in
  earlier stages of Alzheimers or that it alters
  the course of the disease.
• The Medical Letter2003 45116573-4

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Combination Therapy

• Donepezil v. donepezil memantine--moderate to
  severe AD--combined therapy better cognitive
  function, less function deterioration than
  donepezil alone
• Presented at 55th Annual Meeting AA Neurol 2003

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6. Objective measurements of function are not
likely to change enough to be useful with
therapy. Listen to family/caregivers. If they
think it helps, continue the drug.
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7. If one agent doesnt work after 3 months,
consider a second 3-month trial of another agent.
If unsuccessful, discontinue medication.
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Statins

• GP Research Data Base--U.K.
• 3 million enrolled since 1987
• Followed 50-89 y.o.s for development of
  dementia--of those who did
• 3 groups--
• on statins
• elevated lipids, not on statins
• control

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Statins (contd)

• OR of developing dementia if on statin 0.29 (95
  CI0.13-0.63), p 0.002
• Only an association
• But research showing neuro- and endothelial
  protection, antioxidant, anti-platelet and
  anti-inflammatory effects of statins, so they
  should work
• Jick H et al. Lancet 20003561627-31

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Estrogen

• Promotes growth of cholinergic neurons
• Regulates metabolism of amyloid precursor protein
• May delay onset and reduce risk of AD in
  postmenopausal women
• Kawas C, Resnick S, Morrison A et al. Neurology
  1997481517-21
• But, may not
• Shumaker SA,Legault C, Rapp SR et al. JAMA
  2003289(20)2651-62

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NSAIDs

• Evidence of neuroinflammatory response in AD
• Presence of arthritis or use of NSAIDs as
  protective factor
• Possible delay in AD onset or progression of
  symptoms
• Bas A, Ruitenberg A, Hofman A et al. NEJM 2001
  3451515-21

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Other Treatment Options

• Vitamin E 2000 IU qD
• Selegiline 10mg qD (though one trial shows not as
  good as Vit E alone and combination less good
  than either alone
• Sano M,Ernesto C,Thomas RG, et al. NEJM 1997
  3361216-22
• Gingko Biloba 120-240mg qD (Egb 761), some
  trials show modest effect, others none (possibly
  due to amount of active drug in preparations used)

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More on Antioxidants

• Cache County Study, cross-sectional, prospective
  5000 UT residents gt65
• Vit. C and E intake (500-1000mg/400-800IU)
• 36 reduction in AD prevalence at F/U
• Zandi p, Anthony J, Breitner J et al. Reduced
  risk of Alzheimers disease in users of
  antioxidant vitamin supplements the Cache County
  Study. Arch Neurol 200461(1)82-8

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Alzheimers Vaccine

• Designed to produce antibodies to amyloid protein
• Allowed new learning in old mice
• Human trials stopped when several subjects
  developed encephalitis
• More highly purified vaccine is in testing

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Procedural Intervention

• VP shunt
• Decreases level of markers of oxidative stress in
  the CSF
• Cognitive dysfunction stabilized in 11 patients
  over 12 month f/u
• Neurology 2002591139-45
• Registration trial for the shunt beginning with
  256 patients to be enrolled--?

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Behavioral Symptoms

• Look for and treat depression--avoiding Rx with
  strong anticholinergic properties
• Anxiety/agitation--low dose, short acting
  benzodiazepines(lorazepan, oxazepam) or, very low
  dose neuroleptics
• Insomnia--if non-pharmacologic measures fail,
  consider trazodone

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8. Encourage family members, caregivers, the
patient (if able), to read The 36-Hour Dayand
follow the advice.
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9. Insure that the caregiver has a primary
physician and that they are being seen regularly.
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Caregiver Burden

• Alzheimers caregivers spend 69-100 hours per
  week providing care
• Caregivers of patients suffering from dementia
  report more physician visits, more prescribed
  drugs and more hospitalization than controls
• More than 50 of caregivers are depressed

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10. Involve the patient in a respite program
(early on), if possible.
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Resources

• AD Quick Reference Guide for Clinicians and other
  resources--1-800-358-9295
• TriAD Helpline-1-888-874-2343
• www.alz.org
• www.alzheimers.org
• The 36-Hour Day by Peter Rabins and Nancy Mace,
  4th Edition, 2006

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Practice Parameters

• Neurology 2001 561133-42
• Early Detection of Dementia MCI
• Petersen RC, Stevens JC, Genguli M et al
• Neurology 2001 561143-53
• Diagnosis of Dementia
• Knopman DS, DeKosky ST, Cummings JL et al
• Neurology 2001 561154-66
• -Management of Dementia
• Doody RS, Stevens JC, Beck C et al