II. Evaluation: Tools

  1. See Dementia for diagnostic criteria
  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

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 twelve patients have small improvement
        3. One in twelve have adverse effects (Nausea, Diarrhea, Bradycardia)
  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: 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 Exercise
    1. Improves quality of life, physical function, neuropsychiatric symptoms
    2. Teri (2003) JAMA 290:2015-22 +PMID:14559955 [PubMed]
    3. Baker (2010) Arch Neurol 67(1): 71-9 +PMID:20065132 [PubMed]
    4. 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. Occupational Therapy (coping strategies, cognitive aids)
    1. Improves cognition
    2. Graff (2006) BMJ 333(7580):1196 +PMID:17114212 [PubMed]

VI. 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

VII. 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]

VIII. 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. 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]
  3. Selegiline (Eldepryl) 10 mg PO qd
    1. Meta-analysis with not enough evidence to support
      1. Birks (2003) Cochrane Database Syst Rev, CD002854 [PubMed]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. Bacopa monnieri (Brahmi)
    1. No significant evidence to support use
    2. Herbal
  11. 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

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Related Studies

Ontology: Dementia (C0497327)

Definition (MEDLINEPLUS)

Dementia is the name for a group of symptoms caused by disorders that affect the brain. It is not a specific disease. People with dementia may not be able to think well enough to do normal activities, such as getting dressed or eating. They may lose their ability to solve problems or control their emotions. Their personalities may change. They may become agitated or see things that are not there.

Memory loss is a common symptom of dementia. However, memory loss by itself does not mean you have dementia. People with dementia have serious problems with two or more brain functions, such as memory and language. Although dementia is common in very elderly people, it is not part of normal aging.

Many different diseases can cause dementia, including Alzheimer's disease and stroke. Drugs are available to treat some of these diseases. While these drugs cannot cure dementia or repair brain damage, they may improve symptoms or slow down the disease.

NIH: National Institute of Neurological Disorders and Stroke

Definition (MSHCZE) Chronický, trvalý úbytek duševních funkcí a schopností. Za vznik d. zodpovídají tři skupiny onemocnění mozku. Jde o důsledky aterosklerózy s poruchami prokrvení mozku (skupina ischemicko-vaskulárních d.), důsledky jiných chorobných stavů (symptomatické d., např. v důsledku otrav, alkoholismu, d. při AIDS). Nejč. příčinou d. je Alzheimerova nemoc (s některými vzácnějšími chorobami patří do skupiny atroficko-degenerativních onemocnění mozku). D. postihuje inteligenci, kognitivní funkce, vyšší city. Z kognitivního deficitu jsou patrné zhoršení paměti, afázie, apraxie, agnozie, narušení výkonných funkcí. Mizí schopnost soustředění, otupují se zájmy, člověk se nevyzná v čase, je zmatený, bloudí i v nejbližším okolí (dezorientace). Kortikální d. je způsobena postižením kůry (klasicky u Alzheimerovy nemoci), vyznačuje se normální řečí se značně narušenou sémantikou až afázií, amnézií, poruchami zrakové a prostorové orientace. U subkortikální d. (u Parkinsonovy nebo Huntingtonovy nemoci) bývá výrazněji narušena řeč v důsledku motorických poruch, jazykové schopnosti jsou však postiženy málo. Bývá porucha motivace, snížená aktivita, zpomalení duševních pochodů. V případě d. smíšené (např. vaskulární, multiinfarktová d.) lze pozorovat různé kombinace postižení. Průběh je různý – závisí na příčině a ev. včasné léčbě a různý bývá i u jednotlivých typů. Příznaky se vyvíjejí postupně, u některých forem naučené dovednosti a staré vzpomínky dlouho přetrvávají, mizí však schopnost naučit se novému. Léčba d. je farmakologická a důležité jsou rovněž nefarmakologické postupy z oblasti psychoterapie. (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI_NCI-GLOSS) A condition in which a person loses the ability to think, remember, learn, make decisions, and solve problems. Symptoms may also include personality changes and emotional problems. There are many causes of dementia, including Alzheimer disease, brain cancer, and brain injury. Dementia usually gets worse over time.
Definition (NCI) Loss of intellectual abilities interfering with an individual's social and occupational functions. Causes include Alzheimer's disease, brain injuries, brain tumors, and vascular disorders.
Definition (MSH) An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.
Concepts Mental or Behavioral Dysfunction (T048)
MSH D003704
ICD9 294.2, 290
ICD10 F03 , F03.90, F03.9
SnomedCT 192180006, 268675002, 52448006, 88339003
DSM4 294.8
LNC LA10586-8
English Dementia, Amentia, Dementia NOS, Unspecified dementia, [X]Unspecified dementia, dementia (diagnosis), dementia, Amentias, Dementia [Disease/Finding], dementia disorder, dementia disorders, dementias, Dementia, unspecified, [X] Senile dementia, depressed or paranoid type, [X]Senile psychosis NOS, [X]Senile dementia NOS, [X]Primary degenerative dementia NOS, [X] Senile dementia NOS, [X] Senile psychosis NOS, [X] Unspecified dementia, [X] Primary degenerative dementia NOS, [X]Unspecified dementia (disorder), Organic dementia, DEMENTIA, -- Dementia, Dementia (disorder), amentia, Dementia, NOS, Dementias
French DEMENCE, Démence SAI, Amentie, Démence
Portuguese DEMENCIA, Demência NE, Amência, Demência
Spanish DEMENCIA, Amencia, Demencia NEOM, [X]demencia no especificada, [X]demencia no especificada (trastorno), demencia (trastorno), demencia, Demencia
German DEMENZ, Amentia, Demenz NNB, Nicht naeher bezeichnete Demenz, Demenz
Dutch amentie, dementie NAO, Niet gespecificeerde dementie, dementie, Dementia, Dementie
Italian Demenza NAS, Amenzia, Amenza, Demenza
Japanese 認知症NOS, アメンチア, アメンチア, ニンチショウNOS, ニンチショウ, 痴呆状態, 癡呆, 痴呆, 認知症
Swedish Demens
Czech demence, Amence, Demence NOS, Demence
Finnish Dementia
Korean 상세불명의 치매
Polish Demencja, Otępienie, Otępienie przedstarcze, Otępienie starcze
Hungarian Dementia, Amentia, Dementia k.m.n.
Norwegian Demens