Dementia Management

Aka: Dementia Management, Alzheimer Disease Management

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II. Evaluation: Tools

  1. See Dementia Diagnosis
  2. Cognitive Scales
    1. Mini-Mental State Examination
    2. St. Louis University Mental Status (SLUMS)
      1. http://medschool.slu.edu/agingsuccessfully/pdfsurveys/slumsexam_05.pdf
  3. Behavior and Agitation scales
    1. Cohen-Mansfield Agitation Inventory (CMAI)
      1. http://www.dementia-assessment.com.au/symptoms/CMAI_Scale.pdf
  4. Daily Function
    1. Activities of Daily Living Scale (ADL)
    2. Instrumental Activities of Daily Living Scale (IADL)
    3. Functional Activities Questionnaire
  5. Caregiver assessment
    1. Caregiver Burden Scale
  6. Scales used in research
    1. Alzheimer's Disease Assessment Scale (Cognitive)
    2. Behavioral Pathology in Alzheimer's (BEHAVE-AD)
    3. Neuropsychiatric Inventory Questionnaire (NPI-Q)
    4. Clinical Global Impression of Change

III. Management: Non-Pharmacologic measures

  1. Educate patient and family regarding diagnosis
  2. Advance Care Planning
    1. Provide Patient Education and Caregiver decision support regarding Advanced Directives
    2. Address Resuscitation Status (e.g. POLST)
    3. Address Durable Power of Attorney for Health Care
  3. Manage specific concerns in Dementia
    1. Dementia Related Malnutrition
    2. Behavior Problems in Dementia
    3. Agitation in Dementia
    4. Sleep Problems in Dementia
    5. Wandering Behavior in Dementia
  4. Regular physical Exercise
    1. Improves quality of life, physical function, neuropsychiatric symptoms
    2. May increase sleep duration and decrease night awakenings
    3. Teri (2003) JAMA 290:2015-22 +PMID:14559955 [PubMed]
    4. Baker (2010) Arch Neurol 67(1): 71-9 +PMID:20065132 [PubMed]
    5. Pitkala (2013) JAMA Intern Med 173(10):894-901 +PMID:23589097 [PubMed]
  5. Enjoyable leisure activities
    1. Improve neuropsychiatric symptoms, functional capacity, slowing of Memory Loss
    2. Nithianantharajah (2009) Prog Neurobiol 89(4):369-82 +PMID:19819293 [PubMed]
  6. Mental stimulation programs (e.g. puzzles, word games, baking, gardening)
    1. Improves cognition and quality of life
    2. Woods (2012) Cochrane Database Syst Rev (2):CD005562 +PMID:22336813 [PubMed]
  7. Music Therapy
    1. Sing old songs, listen to music, play an instrument, do group Exercise while listening to music
    2. May decrease Agitation, improve social-emotional functioning in the short-term
  8. Reality Orientation
    1. Reorient to time and place to decrease confusion and behavioral symptoms using games, puzzles, calendars
    2. May improve cognitive function
  9. Validation Therapy
    1. Validates patient feelings as opposed to a focus on confusion and Disorientation
    2. May improve contentment and decrease stress and behavioral disorders
  10. Reminiscence Therapy
    1. Recall past experiences, activities and events with the use of photographs, videos and music
    2. May improve mood and emotional disorders
  11. Occupational Therapy (coping strategies, cognitive aids)
    1. Improves cognition
      1. Graff (2006) BMJ 333(7580):1196 +PMID:17114212 [PubMed]
    2. Cognitive rehabilitation improves patient goal attainment
      1. Targeted daily tasks in one-on-one, in-home sessions
      2. Goals focused on greater independence
      3. Bevan (2024) Am Fam Physician 110(1):25-6 [PubMed]

IV. Management: Protocol (monitor Cholinesterase Inhibitors and NMDA Receptor Blockers)

  1. Confirm diagnosis of Alzheimer's Disease
    1. See Dementia
    2. See Altered Level of Consciousness
  2. Complete baseline scales
    1. St. Louis University Mental Status (SLUMS)
      1. http://medschool.slu.edu/agingsuccessfully/pdfsurveys/slumsexam_05.pdf
    2. Mini-Mental State Examination
    3. Activities of Daily Living Scale (ADL)
    4. Instrumental Activities of Daily Living Scale (IADL)
  3. Implement non-pharmacologic measures
    1. See Non-Pharmacologic measures below
  4. Start Acetylcholinesterase Inhibitor (see below)
    1. Titrate medication to most effective dose
    2. Informed Consent with patient and family
      1. Set reasonable expectations
      2. Medications do not typically alter behaviors (e.g. Agitation in Dementia)
      3. Medications offer only modest benefit at best in function
        1. Rate of cognitive decline and outcomes including Nursing Home placement are not affected
        2. One in 12 patients have small improvement
        3. One in 12 have adverse effects (Nausea, Diarrhea, Bradycardia)
          1. One in 16 discontinue medications due to adverse effects
  5. Re-evaluate at 6 month intervals
    1. Repeat scales performed at baseline (MMSE, ADL, IADL)
    2. Indicators to continue Acetylcholinesterase Inhibitor (or NMDA Receptor Blocker)
      1. Patient improved or stable on current agent
      2. Consider adding NMDA Receptor Blocker (Memantine) to Acetylcholinesterase Inhibitor
        1. Combination of agents is unlikely to offer benefit, and may increase adverse effects and cost
        2. Consider instead, switching to NMDA Receptor Blocker (Memantine)
    3. Indicators to switch to other agent
      1. Decline in MMSE (>2 points)
      2. Decline in ADL or IADL
    4. Indicators to discontinue Cholinesterase Inhibitors (or NMDA Receptor Blocker)
      1. Persistent decline in MMSE and ADL or IADL
      2. Intolerable side effects
      3. MMSE <10 with dependency in all ADLs
      4. Severe Dementia with minimal functional capacity (bedridden, non-verbal)
  6. Stopping agents (Acetylcholinesterase Inhibitor, NMDA Receptor Blockers)
    1. Taper medications off over 4 weeks
    2. Abruptly stopping medications risks discontinuation symptoms (e.g. Agitation, Insomnia)

V. Management: Medications

  1. Acetylcholinesterase Inhibitors
    1. Efficacy
      1. See Acetylcholinesterase Inhibitors
      2. Minimal clinical benefit, despite Statistically Significant improvement in cognitive function in trials
      3. Improve neuropsychiatric scores 7 points
        1. Seven point improvement equals ~1 year of decline
        2. Benefits may persist for 1-2 years
        3. Rogers (1998) Arch Intern Med 158:1021-31 [PubMed]
      4. Meta-analysis shows marginal benefit to risk ratio
        1. Where NNT is Number Needed to Treat
        2. NNT for global improvement: 10
        3. NNT for cognitive improvement: 12
        4. NNT for significant side effects to stop med: 16
        5. Lanctot (2003) CMAJ 169:557-64 [PubMed]
    2. Agents
      1. Donepezil (Aricept): Preferred agent
        1. Dose: Start at 5 mg orally at bedtime and increase to 10 mg after 4-6 weeks
        2. Delays Nursing Home placement by 17-21 months
        3. Geldmacher (2003) J Am Geriatr Soc 51:937-44 [PubMed]
      2. Galantamine (Reminyl)
        1. Dose: Start immediate release 4 mg orally twice daily OR extended release 8 mg orally daily
      3. Rivastigmine (Exelon)
        1. Dose: Start 1.5 mg orally twice daily OR 4.6 mg transdermal patch every 24 hours
        2. Adverse effects limit use (new patch may be better tolerated)
    3. Adverse Effects
      1. Side effects (Nausea, Diarrhea, Bradycardia) may limit use
  2. N-Methyl-D-Aspartate (NMDA) Receptor Blocker - Memantine (Namenda, Ebixa in Europe)
    1. Dose: Start 5 mg orally daily and titrate to 10 mg orally twice daily
    2. Indicated only in moderate to severe Dementia
      1. Can improve cognition and function
      2. Consider as alternative to Cholinesterase Inhibitor (e.g. Aricept) if side effects limit use
        1. Memantine may be better tolerated than Cholinesterase Inhibitors
      3. Some studies support the use of combination therapy with Cholinesterase Inhibitors
        1. Matsuzuno (2015) J Alzheimers Dis 45(3):771-80 +PMID:25624417 [PubMed]
        2. Matsunga (2014) Int J Neuropsychopharmacol 18(5) +PMID:25548104 [PubMed]
        3. Gareri (2014) J Alzheimers Dis 41(2):633-40 +PMID:24643135 [PubMed]
        4. Tariot (2004) JAMA 291:317-24 [PubMed]
      4. Other studies showed low efficacy (only helped 1 in 12)
        1. Also, combination therapy has additional adverse effects (GI, Bradycardia, Syncope)
        2. Howard (2012) N Engl J Med 366(10):893-903 +PMID:22397651 [PubMed]
        3. (2012) Presc Lett 19(5):28

VI. Management: Other Medications with Potential Benefit

  1. Vitamin E
    1. Dose: 1000 IU orally twice daily
    2. Precautions
      1. Variable evidence to support use in Alzheimer's Disease
      2. Vitamin E in excess of 400 IU/day has been associated with overall increased mortality
      3. Vitamin E is associated with an increased risk of bleeding and Hemorrhagic Stroke
        1. Do not use >800 IU/day in patients on Warfarin or antiplatelet agents
      4. (2014) Presc Lett 21(2):12
    3. May slow functional decline in mild to moderate Dementia (in those on Cholinesterase Inhibitor)
      1. Dysken (2014) JAMA 311(1):33-44 [PubMed]
    4. Initial studies showed slower functional decline
      1. Sano (1997) N Engl J Med 336:1216-22 [PubMed]
    5. Insufficient evidence to recommend by Cochrane
      1. Tabet (2003) Cochrane Database Syst Rev, CD002854 [PubMed]
  2. Selective Serotonin Reuptake Inhibitors (SSRI)
    1. Treat comorbid depression
    2. Significant impact on quality of life
    3. References
      1. Lyketsos (2003) Arch Gen Psychiatry 60:737-46 [PubMed]

VII. Management: Medications to avoid (due to risk or lack of benefit)

  1. Aducanumab (Aduhelm)
    1. Monoclonal Antibody infused IV every 4 weeks at a cost of $28,200 to $56,000 per year
    2. May reduce amyloid beta Plaque, but does not appear to improve cognitive function
    3. Risk of CNS microhemorrhages and edema requiring 3 MRIs in first year of use
    4. FDA approved, over-riding its own advisory committee's vote (10 against and 1 in favor) to not approve
    5. (2021) Presc Lett 28(8): 43
    6. Walsh (2021) BMJ 374:n1682 [PubMed]
  2. Lecanemab (Leqembi)
    1. Another Monoclonal Antibody infused IV every 2 weeks at a cost of $26,500 per year
    2. Risk of CNS microhemorrhages (NNH 15) and edema requiring 3 MRIs in first 18 months of use
    3. May reduce amyloid beta Plaque, but does not appear to improve cognitive function
    4. As with Aducanumab, FDA approved via the accelerated approval pathway
    5. (2023) Presc Lett 30(4): 24
  3. NSAIDs: No benefit in prospective trials
    1. Netherlands Study (n=6989 over age 55, for 8 years)
      1. Continuous NSAID use decreased Alzheimer's risk
      2. Relative Risk Reduction 80% for >2 years of use
      3. Aspirin did not confer same benefit as NSAID use
      4. Veld (2001) N Engl J Med 345:1515-21 [PubMed]
    2. Johns Hopkins Retrospective study (n=209)
      1. NSAIDS (n=32) slowed Alzheimer's progression
      2. Based on MMSE, Boston Naming, and Benton scales
      3. Rich (1995) Neurology 45:51-5 [PubMed]
    3. Recent evidence does not support routine use
      1. Cummings (2004) N Engl J Med 351:56-67 [PubMed]
  4. Selegiline (Eldepryl) 10 mg PO qd
    1. Meta-analysis with not enough evidence to support
      1. Birks (2003) Cochrane Database Syst Rev, CD002854 [PubMed]
  5. Hormone Replacement Therapy
    1. Testosterone Replacement
    2. ` Risk of adverse effects and no significanr benefit demonstrated to date
      1. Lu (2006) Arch Neurol 63(2): 177-85 [PubMed]
    3. Estrogen Replacement
      1. Initial studies showed possible benefit
      2. Recent studies have shown no benefit or worsening
      3. References
        1. Buckwalter (2004) J Am Geriatr Soc 52:182-6 [PubMed]
        2. Espeland (2004) JAMA 291:2959-68 [PubMed]
  6. Statins
    1. No significant effect on cognition or functional status in moderate Alzheimer Disease
    2. Sano (2011) Neurology 77(6): 556-63 [PubMed]
    3. Feldman (2010) Neurology 74(12): 956-64 [PubMed]
  7. Ginkgo Biloba 40 mg PO tid
    1. No significant longterm benefit despite initial studies suggesting possible mild improvement
    2. Case reports of coma, bleeding, and Seizures
    3. High drop out rate in studies
    4. References
      1. Le Bars (1997) JAMA 278: 1327-32 [PubMed]
      2. Oken (1998) Arch Neurol 55:1409-15 [PubMed]
  8. Omega-3 Fatty Acids
    1. No significant effect on cognition or functional status in moderate Alzheimer Disease
    2. Quinn (2010) JAMA 304(17): 1903-11 +PMID:21045096 [PubMed]
  9. Light Alcohol consumption (1-6 drinks per week)
    1. Appears to have protective effect against Dementia
    2. However also has negative cognitive effects
    3. Mukamal (2003) JAMA 289:1405-13 [PubMed]
  10. Coconut oil (Axona)
    1. In theory, brain has altered Glucose Metabolism, and Triglycerides offer alternative nutritional source
    2. No significant evidence to support this use
    3. Risk of increased fat (and calorie intake) - 12 grams of fat per tablespoon
    4. Radenahmad (2011) Br J Nutr 105(5):738-46 [PubMed]
  11. Bacopa monnieri (Brahmi)
    1. No significant evidence to support use
    2. Herbal
  12. Prevagen (apoaquorin)
    1. Calcium binding Protein derived from Jellyfish extract
    2. Postulated to be neuroprotective
    3. Associated with adverse effects in some patients (Seizures, strokes)
    4. No evidence of benefit (and FDA required re-labeling and patient restitution in 2020)
    5. (2015) Presc Lett 22(11):65
    6. (2020) Presc Lett 27(11):64

VIII. References

  1. (2020) Presc Lett 27(7): 38
  2. Cummings (2002) Am Fam Physician 65(12):2525-34 [PubMed]
  3. Cummings (2004) N Engl J Med 351:56-67 [PubMed]
  4. Delagarza (2003) Am Fam Physician 68(7):1365-72 [PubMed]
  5. Delagarza (1998) Am Fam Physician 58(5):1175-82 [PubMed]
  6. Epperly (2017) Am Fam Physician 95(12): 771-8 [PubMed]
  7. Jaqua (2024) Am Fam Physician 110(3): 281-93 [PubMed]
  8. Sloane (1998) Am Fam Physician 58(7):1577-86 [PubMed]
  9. Tariot (1997) Postgrad Med 101(6):73-90 [PubMed]
  10. Winslow (2011) Am Fam Physician 83(12): 1403-12 [PubMed]

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