eMedicine Specialties > Neurology > Behavioral Neurology and Dementia

Alzheimer Disease: Treatment & Medication

Author: Heather S Anderson, MD, Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical Center
Contributor Information and Disclosures

Updated: Aug 27, 2009

Treatment

Medical Care

Therapeutic approaches to Alzheimer disease will someday include both symptomatic therapy and disease-modifying therapies. To date, only symptomatic therapies are available. All approved drugs for the treatment of Alzheimer disease modulate neurotransmitters - either acetylcholine or glutamate. Disease-modifying therapies would delay the onset of disease and/or slow the rate of progression. Although phase III trials for several potential disease-modifying therapies have been completed, as of August 2008, none have been clearly shown to be efficacious and hence none have been approved in the United States by the FDA.  

The standard medical treatment for Alzheimer disease includes cholinesterase inhibitors (ChEIs) and partial N -methyl-D-aspartate (NMDA) antagonists. 

Psychotropic medications are often used to treat secondary symptoms of Alzheimer disease such as depression, agitation, and sleep disorders. These include antidepressants, anti-epileptic drugs used for their effects on behavior, and neuroleptics. Several studies have examined the efficacy of psychotropic drugs; most have demonstrated no or limited efficacy, but many issues make interpretation of data from these studies difficult. 

  • Cholinesterase inhibitors
    • Numerous lines of evidence suggest that cholinergic systems that modulate information processing in the hippocampus and neocortex are impaired early in the course of Alzheimer disease. 
    • These observations have suggested that some of the clinical manifestations of Alzheimer disease are due to loss of cholinergic innervation to the cerebral cortex. Centrally-acting acetylcholinesterase inhibitors (ChEIs) prevent the breakdown of acetylcholine. 
    • Patients on ChEIs decline more slowly on cognitive and functional measures than patients on placebo. Nonetheless, as the treatment is symptomatic, it cannot be concluded that the underlying rate of progression of Alzheimer disease is affected.
    • Centrally acting anticholinergic medications should be avoided. Patients not uncommonly receive both ChEIs and anticholinergic agents, which counteract each other. Medications with anticholinergic effects such as diphenhydramine (Benadryl) and tricyclic antidepressants (such as amitriptyline or nortriptyline) can cause cognitive dysfunction. Therefore, a careful listing of the patient's medications is important to reduce the doses of, or ideally eliminate, all centrally acting anticholinergic agents. 
    • See also the Medication section.
  • N -methyl-D-aspartate antagonists: The partial NMDA antagonist memantine (Namemda) is believed to work by improving the signal-to-noise ratio of glutamatergic transmission at the NMDA receptor. This agent is approved by the FDA for treating moderate and severe Alzheimer disease. Several studies have demonstrated that memantine can be safely used in combination with ChEIs.
  • Antidepressants: Antidepressants have an important role in the treatment of mood disorders in patients with Alzheimer disease. Depression is observed in more than 30% of patients with Alzheimer disease, and it frequently begins before Alzheimer disease is clinically diagnosed. Therefore, palliation of this frequent comorbid condition may improve cognitive and noncognitive performance. Other mood modulators, such as valproic acid, can be helpful for the treatment of disruptive behaviors and outbursts of anger, which patients with moderately advanced or advanced stages of Alzheimer disease may have.
  • Psychotropic medications and behavioral interventions
    • A variety of behavioral and pharmacologic interventions can temporarily alleviate clinical manifestations of Alzheimer disease, such as anxiety, agitation, depression, and psychotic behavior. The effectiveness of such interventions is often modest and temporary, and they do not prevent the eventual deterioration of the patient's condition.
    • Behavioral interventions range from patient-centered approaches to caregiver training to help manage cognitive and behavioral manifestations of Alzheimer disease. These interventions are often combined with the more widely used pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for aberrant and/or socially disruptive behavior, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). 
    • No specific agent or dose of individual agents is unanimously accepted for the wide array of clinical manifestations. At present, the US Food and Drug Administration (FDA) has not approved any psychotropic agent for the treatment of Alzheimer disease. In 2005, the FDA decided to add a "black box warning" on the use of atypical neuroleptics in the treatment of secondary symptoms of Alzheimer disease such as agitation. Analyses suggested that patients on atypical neuroleptics had increased risk of death or stroke compared with patients on placebo.

      As of August 2008, the FDA has not added a black box warning for older neuroleptics such as haloperidol; yet few clinicians believe these older drugs are more efficacious and safer than the atypical neuroleptics because randomized clinical trials are lacking or are difficult to apply to specific clinical settings. Medications that many practitioners prefer are risperidone, olanzapine, and quetiapine. Physicians using these drugs are advised to tell patients (when appropriate) and caregivers of potential risks, but indicate that these drugs may still be the best choice in their individual case. 
  • The general recommendation is to use such agents as infrequently as possible and at the lowest doses possible to minimize adverse effects, particularly in frail, elderly patients. 
  • Particular concern has been raised about the potential for dopamine-depleting agents to aggravate the motor manifestations of dementia with Lewy bodies (DLB), because patients with DLB may be extremely sensitive to these agents. 
  • Results of several studies indicate that anticonvulsants (eg, gabapentin, valproic acid) may have a role in the treatment of behavioral problems in patients with Alzheimer disease.
  • Many studies have suggested that intense inflammation occurs in the brains of patients with Alzheimer disease. Epidemiologic studies suggest that some patients on chronic anti-inflammatory therapy have a decreased risk of developing Alzheimer disease. Nonetheless, no randomized clinical trial of greater than 6-months duration has demonstrated efficacy of anti-inflammatory drugs in slowing the rate of progression of Alzheimer disease. 
  • No data exist showing that women with Alzheimer disease who are then placed on estrogen therapy (ET) have fewer symptoms or progress more slowly than women treated with a placebo. Furthermore, a randomized clinical trial of estrogen in cognitively normal women aged 65 and older with a first-degree relative with Alzheimer disease showed that ET might actually increase the risk of stroke and dementia. Whether ET might decrease risk if started well before the age of 65 is not known.
  • Excess levels of free radicals in the brain are neurotoxic. Nonetheless, no study has demonstrated efficacy of free-radical scavengers in the treatment of the cognitive symptoms of Alzheimer disease. 
  • In the past 10 years, numerous studies have been conducted, and many are still ongoing, that test therapies designed to decrease toxic amyloid fragments in the brain. A wide variety of approaches have been tried. These include vaccination with amyloid species, administration of monoclonal anti-amyloid antibodies, administration of intravenous immune globulin that may contain amyloid-binding antibodies, selective amyloid-lowering agents, chelating agents to prevent amyloid polymerization, brain shunting to improve removal of amyloid, and beta-secretase inhibitors to prevent generation of the A-beta amyloid fragment, among others. To date, no phase III study with these approaches has shown an acceptable combination of efficacy and acceptable side effects.
  • Studies are also ongoing with agents that may prevent or reverse excess tau phosphorylation and thereby diminish formation of neurofibrillary tangles.
  • Brain changes associated with Alzheimer disease probably start decades before clinical dementia is apparent. Many investigators believe that disease-modifying therapies are much more likely to be effective if they are started in a presymptomatic stage. Studies are identifying patients at increased risk with neuropsychological, neuroimaging, and genetic methods. Some of the disease-modifying therapies discussed above may possibly be effective if started in presymptomatic patients.

Surgical Care

No accepted surgical treatments exist for Alzheimer disease. Potential surgical treatments in the future may include the use of devices to infuse neurotrophic factors, such as growth factors, to palliate Alzheimer disease.

Diet

No special dietary considerations exist for Alzheimer disease.

Activity

Both physical and mental activities are recommended for patients with Alzheimer disease.

  • Mental activity
    • Many patients with normal cognition or those with mild impairment are concerned that they may develop Alzheimer disease. Many experts believe that mentally challenging activities, such as doing crossword puzzles and brainteasers, may reduce the risk in such patients. 
    • Whether working on crossword puzzles or similar games for patients who already have Alzheimer disease might slow the rate of progression is not known. Clinical trials are underway to determine the effect these cognitive activities have on Alzheimer disease progression. 
    • The mental activities should be kept within a reasonable level of difficulty for the patient. They should preferably be interactive, and they should be designed to allow the patient to recognize and correct mistakes.
    • Most important, these activities should be administered in a manner that does not cause excessive frustration and that ideally motivates the patient to engage in them frequently.
    • Unfortunately, little standardization and rigorous testing has been done to validate this treatment modality.
    • Some investigators have attempted various forms of cognitive retraining, also known as cognitive rehabilitation. The results of this approach remain controversial, and a substantial experimental study must still be performed to determine if it is useful in Alzheimer disease.
  • Physical activity: Routine physical activity and exercise may have an impact on Alzheimer disease progression. Exercise training has been associated with some improvement in cognitive function in patients with dementia17 and physical activity in mid-life is associated with a reduced risk of developing Alzheimer disease in late-life.18

Medication

The mainstay of therapy for patients with Alzheimer disease is the use of centrally acting cholinesterase inhibitors to attempt to compensate for the depletion of ACh in the cerebral cortex and hippocampus. Four ChEIs have been approved by the FDA in the United States for the treatment of AD—tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne, formerly Reminyl). Tacrine has potential liver toxicity, requires frequent blood monitoring, and has been rarely prescribed since the other agents have become available. All 4 drugs inhibit acetylcholinesterase at the synapse (specific cholinerase). The drugs tacrine and rivastigmine also inhibit butyrylcholinesterase. Although butyrylcholinesterase levels may be increased in AD, it is not clear that rivastigmine or tacrine have greater clinical efficacy than donepezil and galantamine. 

Galantamine has a different second mechanism of action; it is also a presynpatic nicotinic modulator. No data exist that this second mechanism is of clinical importance.

In a multicenter, randomized, placebo-controlled trial, donepezil (5 mg/d for 6 wk, then 10 mg/d for 42 wk) was compared with placebo to measure change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) in patients with mild cognitive impairment. A small, but significant, improvement on the primary measure of cognition was observed. No change was observed on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in mild cognitive impairment (MCI). Responses on subjective measures suggest subjects perceived benefits with donepezil treatment. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%).19

All ChEIs have shown modest benefit compared with placebo on measures of cognitive function and activities of daily living. The ChEIs may also alleviate the noncognitive manifestations of AD such as agitation, wandering, and socially inappropriate behavior.

In general, the benefits are temporary because ChEIs do not address the underlying cause of the degeneration of cholinergic neurons, which continues during the disease. Although the ChEIs were originally expected to be efficacious in only the early and intermediate stages of AD (because the cholinergic deficit becomes more severe later in disease and fewer intact cholinergic synapses are present), they are also helpful in advanced disease. Furthermore, ChEIs are helpful in patients with AD with concomitant infarcts and in patients with dementia with Lewy bodies. (Frequently, AD and dementia with Lewy bodies occur in the same patient; sometimes this is called the Lewy body variant of AD).

The ChEIs share a common profile of adverse effects, the most frequent of which are nausea, vomiting, diarrhea, and dizziness. These are typically dose related and can be mitigated with slow uptitration to the desired maintenance dose. As antimuscarinic drugs are used for the treatment of incontinence, logically, ChEIs might exacerbate incontinence. One brief report has supported this hypothesis.20

ChEIs prescribed to treat dementia can provoke symptomatic bradycardia and syncope and precipitate fall-related injuries, including hip fracture. A population-based cohort study that identified community-dwelling older adults with dementia who were taking cholinesterase inhibitors (n=19,803) and controls who were not (n=61,499) found hospital visits for syncope were more frequent in people receiving ChEIs than in controls (31.5 vs 18.6 events per 1000 person-years; adjusted hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.57-1.98). Other syncope-related events, including hospital visits for bradycardia, permanent pacemaker insertion, and hip fracture, were also more common among people receiving cholinesterase inhibitors compared with controls. ChEI use in older adults with dementia is associated with increased risk of syncope-related events; these risks must be weighed against the benefits of taking ChEIs.21

Anecdotal reports exist of acute cognitive and behavioral decline associated with the abrupt termination of ChEIs. In several of these cases, restarting the ChEI was not associated with substantial improvement. These reports have implications concerning the best practice when switching a patient from one ChEI to another in this class. Reasons for switching might include undesirable side effects or seeming lack of efficacy. Nonetheless, no published data help clinicians know when switching to another ChEI would be helpful. The common practice of tapering a patient off one CNS-active medication before starting a new one should not be followed when changing ChEIs. For example, a patient who had been taking 10 mg of donepezil should be started the next day on galantamine, at least 8 mg/d and possibly 16 mg/d. 

No current evidence supports the use of more than 1 ChEI at a time. 

A report by Sano et al in 1997 suggested that high dose vitamin E (2000 units per day of alpha-tocopherol) might decrease the risk of death or the rate of conversion to severe dementia. This benefit presumably resulted from the antioxidant effects of vitamin E. Nonetheless, later studies suggest that vitamin E supplementation may actually increase risk of adverse cardiovascular outcomes. Therefore, use of these agents is not currently recommended, and most practitioners have abandoned their use.

NMDA antagonists

The newest class of agents indicated for the treatment of AD. As of July 2008, the only approved drug in this class is memantine. These agents may be used alone or combined with AChE inhibitors. Studies suggest memantine use with donepezil has an effect on cognition in moderate to severe AD22 but not with mild to moderate AD.23


Memantine (Namenda, Axura)

NMDA antagonist indicated for all stages of AD. NMDA-receptor overstimulation in CNS by glutamate (excitatory amino acid) may contribute to symptoms; no evidence confirms glutamatergic deficit in AD.

Adult

5 mg PO qd, gradually titrate to 20-mg/d target dose as follows (allow > 1 wk between increases): 5 mg PO bid, 5 mg PO q am, 10 mg PO q pm, 10 mg PO bid

Pediatric

Not indicated

Coadministration with drugs causing alkaline urine (eg, sodium bicarbonate, carbonic anhydrase inhibitors) may decrease clearance by 80%, leading to accumulation and toxicity; coadministration with other NMDA antagonists (eg, amantadine, ketamine, dextromethorphan) may increase toxicity; concurrent use with another drug eliminated via renal tubular secretion (eg, hydrochlorothiazide, triamterene, cimetidine, ranitidine, quinidine, nicotine) may alter plasma levels of both

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Common adverse effects are dizziness (7%), headache (6%), and constipation (5%); predominantly excreted renally, no data support use in severe renal impairment

Centrally acting AChE inhibitors

These agents are used to palliate cholinergic deficiency.


Donepezil (Aricept)

Centrally acting AChE but not BuChE inhibitor

Adult

5 mg PO qd for 3-4 wk, the 10 mg PO qd

Pediatric

Not established

Increases effects of succinylcholine, ChEIs, or cholinergic agonists; may increase fluvoxamine levels

Documented hypersensitivity; sick sinus syndrome, other supraventricular cardiac conduction abnormalities; peptic ulcer disease; bladder outflow obstruction

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with seizures, asthma, sick sinus syndrome, or other supraventricular conduction abnormalities


Rivastigmine (Exelon)

Centrally acting AChE and BuChE inhibitor.

Adult

1.5 mg PO bid for 1 mo, 3 mg PO bid for 1 mo, 4.5 mg PO for 1 mo, then 6 mg PO bid thereafter

Pediatric

Not established

None reported; metabolized by cholinesterases (no significant hepatic metabolism)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Administer with large meals to minimize adverse effects; titrate up slowly


Rivastigmine transdermal patch (Exelon patch)

Competitive and reversible acetylcholinesterase inhibitor. While mechanism of action unknown, may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of acetylcholine available for synaptic transmission in CNS and thereby enhance cholinergic function. Effect may lessen as disease process advances and fewer cholinergic neurons remain functionally intact.
Available as 5-cm2 patch containing 9 mg (releases 4.6 mg/24 h) and 10-cm2 patch containing 18 mg (releases 9.5 mg/24 h). Indicated for dementia of Alzheimer disease and for dementia associated with Parkinson disease.

Adult

Apply patch to upper or lower back, upper arm, or chest
Initiating patch therapy (not switching from oral therapy): 4.6 mg/24 h patch (5 cm2) applied qd initially; if well tolerated and after minimum of 4 wk, increase to 9.5 mg/24 h patch (10 cm2) applied qd
Switching from oral administration to patch therapy:
Apply first patch on day following last oral dose
Total daily oral dose <6 mg/d: Switch to 4.6 mg/24 h patch
Total daily oral dose 6-12 mg/d: Switch to 9.5 mg/24 h patch

Pediatric

Not indicated

May reduce effects of anticholinergics; increases effects of cholinergic agonists and neuromuscular blockers; risk of bradycardia increases when administered concurrently with beta-blockers without ISA, the calcium channel blockers diltiazem or verapamil, and digoxin

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Apply patch to clean, dry, and hairless area of back, upper arm, or chest; area where patch is applied must be free of powder, oil, moisturizer, lotion, or other substances that would keep patch from adhering properly to skin; also, apply to areas free of cuts, rashes, or other irritation; may cause significant nausea, vomiting, anorexia, and weight loss if taken in doses higher than recommended; if significant adverse effects occur, patient should discontinue treatment for several doses, then restart at lowest dose; extrapyramidal symptoms may occur or be exacerbated (especially tremor); caution in history of peptic ulcer disease, sick sinus syndrome, urinary obstruction, pulmonary conditions (eg, COPD, asthma), and bradycardia or supraventricular conduction conditions


Galantamine (Razadyne, Razadyne ER)

Enhances central cholinergic function; likely to inhibit AChE.

Adult

IR: 16-24 mg/d PO divided bid
ER: 16-24 mg PO qd

Pediatric

Not established

Can interfere with effect of anticholinergics; synergistic effect if given with other ChEIs, succinylcholine, or other neuromuscular blocking agents

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Most frequent adverse events are nausea, vomiting, diarrhea, anorexia, and weight loss; dose titration needed in patients with hepatic and/or renal dysfunction; can cause bladder outflow obstruction; prescribe with care in patients with lung disease; could potentiate tendency for seizures

More on Alzheimer Disease

Overview: Alzheimer Disease
Differential Diagnoses & Workup: Alzheimer Disease
Treatment & Medication: Alzheimer Disease
Follow-up: Alzheimer Disease
References
[ CLOSE WINDOW ]

References

  1. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1-2):125-32. [Medline].

  2. Wimo, A; Winblad, B; Jonsson, L. An estimate of the total worldwide societal costs of dementia in 2005. Alzheimer's & Dementia. 2007;3:81-91.

  3. Hebert LE, Scherr PA, Bienias JL, et al. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. Aug 2003;60(8):1119-22. [Medline].

  4. Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiat. 1907;64:146-8.

  5. Braak H, Braak E, Grundke-Iqbal I, et al. Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett. Apr 24 1986;65(3):351-5. [Medline].

  6. Fitzpatrick AL, Kuller LH, Ives DG, et al. Incidence and prevalence of dementia in the Cardiovascular Health Study. J Am Geriatr Soc. Feb 2004;52(2):195-204. [Medline].

  7. Evans DA, Bennett DA, Wilson RS, et al. Incidence of Alzheimer disease in a biracial urban community: relation to apolipoprotein E allele status. Arch Neurol. Feb 2003;60(2):185-9. [Medline].

  8. Shadlen MF, Siscovick D, Fitzpatrick AL, et al. Education, cognitive test scores, and black-white differences in dementia risk. J Am Geriatr Soc. Jun 2006;54(6):898-905. [Medline].

  9. Tang MX, Cross P, Andrews H, et al. Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology. Jan 9 2001;56(1):49-56. [Medline].

  10. Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C. Age, neuropathology, and dementia. N Engl J Med. May 28 2009;360(22):2302-9. [Medline].

  11. Cechetto DF, Hachinski V, Whitehead SN. Vascular risk factors and Alzheimer's disease. Expert Rev Neurother. May 2008;8(5):743-50. [Medline].

  12. Razay G, Vreugdenhil A, Wilcock G. The metabolic syndrome and Alzheimer disease. Arch Neurol. Jan 2007;64(1):93-6. [Medline].

  13. Swerdlow RH, Khan SM. A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Med Hypotheses. 2004;63(1):8-20. [Medline].

  14. Swerdlow RH. Pathogenesis of Alzheimer's disease. Clin Interv Aging. 2007;2(3):347-59. [Medline].

  15. Lee HG, Zhu X, Castellani RJ, et al. Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses. J Pharmacol Exp Ther. Jun 2007;321(3):823-9. [Medline].

  16. [Best Evidence] Green RC, Roberts JS, Cupples LA, Relkin NR, Whitehouse PJ, Brown T, et al. Disclosure of APOE genotype for risk of Alzheimer's disease. N Engl J Med. Jul 16 2009;361(3):245-54. [Medline].

  17. Heyn P, Abreu BC, Ottenbacher KJ. The effects of exercise training on elderly persons with cognitive impairment and dementia: a meta-analysis. Arch Phys Med Rehabil. Oct 2004;85(10):1694-704. [Medline].

  18. Friedland RP, Fritsch T, Smyth KA, et al. Patients with Alzheimer's disease have reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci U S A. Mar 13 2001;98(6):3440-5. [Medline].

  19. [Best Evidence] Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. May 5 2009;72(18):1555-61. [Medline].

  20. Starr JM. Cholinesterase inhibitor treatment and urinary incontinence in Alzheimer's disease. J Am Geriatr Soc. May 2007;55(5):800-1. [Medline].

  21. [Best Evidence] Gill SS, Anderson GM, Fischer HD, Bell CM, Li P, Normand SL, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med. May 11 2009;169(9):867-73. [Medline].

  22. Schmitt FA, van Dyck CH, Wichems CH, et al. Cognitive response to memantine in moderate to severe Alzheimer disease patients already receiving donepezil: an exploratory reanalysis. Alzheimer Dis Assoc Disord. Oct-Dec 2006;20(4):255-62. [Medline].

  23. Porsteinsson AP, Grossberg GT, Mintzer J, et al. Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res. Feb 2008;5(1):83-9. [Medline].

  24. Breitner JC, Haneuse S, Walker R, Dublin S, Crane PK, Gray SL, et al. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology. Jun 2 2009;72(22):1899-1905.

  25. Alzheimer A. Uber eine eigenartige Erkankung der Hirnrinde. Allg Z Psychiatr. 1907;64:146.

  26. Braak H, Braak E. Ratio of pyramidal cells versus non-pyramidal cells in the human frontal isocortex and changes in ratio with ageing and Alzheimer's disease. Prog Brain Res. 1986;70:185-212. [Medline].

  27. Crook R, Verkkoniemi A, Perez-Tur J, et al. A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1. Nat Med. Apr 1998;4(4):452-5. [Medline].

  28. Crystal HA, Horoupian DS, Katzman R, et al. Biopsy-proved Alzheimer disease presenting as a right parietal lobe syndrome. Ann Neurol. Aug 1982;12(2):186-8. [Medline].

  29. Du Y, Dodel R, Hampel H, et al. Reduced levels of amyloid beta-peptide antibody in Alzheimer disease. Neurology. Sep 11 2001;57(5):801-5. [Medline].

  30. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. Nov 1975;12(3):189-98. [Medline].

  31. Frisoni GB, Padovani A, Wahlund LO. The diagnosis of Alzheimer disease before it is Alzheimer dementia. Arch Neurol. Jul 2003;60(7):1023; author reply 1023-4. [Medline].

  32. Gilman S, Koller M, Black RS, et al. Clinical effects of A{beta} immunization (AN1792) in patients with AD in an interrupted trial. Neurology. Apr 7 2005.

  33. Hamdy RC. Alzheimer's disease: an overview. South Med J. Jul 2001;94(7):661-2. [Medline].

  34. Hof PR, Morrison JH. The cellular basis of cortical disconnection in Alzheimer's disease and related dementing conditions. In: Terry RD, Katzman R, Bick KL, eds. Alzheimer's Disease. New York: Lippincott Raven; 1994:197-229.

  35. Irizarry MC, Hyman BT. Alzheimer disease therapeutics. J Neuropathol Exp Neurol. Oct 2001;60(10):923-8. [Medline].

  36. Jönsson L, Jonsson B, Wimo A, et al. Second International Pharmacoeconomic Conference on Alzheimer' s Disease. Alzheimer Dis Assoc Disord. Jul-Sep 2000;14(3):137-40. [Medline].

  37. Katzman R. Alzheimer's disease. N Engl J Med. Apr 10 1986;314(15):964-73. [Medline].

  38. Kuljis RO. Modular corticocerebral pathology in Alzheimer's disease. In: Mangone CA, Allegri RF, Ariza, eds. Dementia: A Multidisciplinary Approach. 1997:143-55.

  39. Kuljis RO. Lesions in the pulvinar in patients with Alzheimer's disease. J Neuropathol Exp Neurol. Mar 1994;53(2):202-11. [Medline].

  40. Maelicke A, Albuquerque EX. Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer's disease. Eur J Pharmacol. Mar 30 2000;393(1-3):165-70. [Medline].

  41. Mayeux R, Sano M. Treatment of Alzheimer's disease. N Engl J Med. Nov 25 1999;341(22):1670-9. [Medline].

  42. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. Jul 1984;34(7):939-44. [Medline].

  43. Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. Apr 1991;41(4):479-86. [Medline].

  44. Moretti R, Torre P, Antonello RM, et al. Gabapentin as a possible treatment of behavioral alterations in Alzheimer disease (AD) patients. Eur J Neurol. Sep 2001;8(5):501-2. [Medline].

  45. Raskind MA, Peskind ER, Wessel T, et al. Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology. Jun 27 2000;54(12):2261-8. [Medline].

  46. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. Nov 1984;141(11):1356-64. [Medline].

  47. Selkoe DJ. Treating Alzheimer's disease: a new era begins. Neurol Alert. 2000;18:81-2.

  48. Slagle MA. Featured CME topic: dementia. Medication update. South Med J. Jul 2001;94(7):678-81. [Medline].

  49. Talesa VN. Acetylcholinesterase in Alzheimer's disease. Mech Ageing Dev. Nov 2001;122(16):1961-9. [Medline].

  50. Tariot PN, Solomon PR, Morris JC, et al. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology. Jun 27 2000;54(12):2269-76. [Medline].

  51. Tomlinson BE. Ageing and the dementias. In: Hume Adams J, Duchen LW, eds. Greenfield's Neuropathology. New York: Oxford Press; 1992:1284-410.

  52. Verkkoniemi A, Somer M, Rinne JO, et al. Variant Alzheimer's disease with spastic paraparesis: clinical characterization. Neurology. Mar 14 2000;54(5):1103-9. [Medline].

  53. von Gunten A, Kovari E, Rivara CB, et al. Stereologic analysis of hippocampal Alzheimer's disease pathology in the oldest-old: evidence for sparing of the entorhinal cortex and CA1 field. Exp Neurol. May 2005;193(1):198-206. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Alzheimer’s disease, dementia, cognitive impairment, Alzheimer's disease signs and symptoms, Alzheimer's disease treatment, senile dementia of the Alzheimer type, Alzheimer dementia, Alzheimer's dementia, AD, primary neuronal degeneration, senile plaques, SP, neurofibrillary tangles, NFT, cerebrocortical atrophy, central nervous system, CNS, acetylcholine, acetylcholinesterase, butyrylcholinesterase, NMDA, memantine

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Heather S Anderson, MD, Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical Center
Heather S Anderson, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Central Plains Geriatric Education Center Honoraria Speaking and teaching

Medical Editor

Joseph Quinn, MD, Assistant Professor, Department of Neurology, Portland VA Medical Center, Oregon Health Sciences University
Joseph Quinn, MD is a member of the following medical societies: American Academy of Neurology, Society for Neuroscience, and Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Medivations Honoraria Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.