Highlights & Basics
- Alzheimer disease (AD) is a chronic, progressive neurodegenerative disorder characterized by a global, nonreversible impairment in cerebral functioning.
- AD is characterized by memory loss, loss of social and occupational functioning, diminished executive function, speech and motor deficits, personality change, and behavioral and psychological disturbance.
- It has a deteriorating course over up to 8-10 years.
- Brain lesions are marked by neurofibrillary tangles, senile plaques, neuronal loss, and brain atrophy, with defects in acetylcholine synthesis at the cellular level.
- Treatment requires a multidisciplinary approach with increasing emphasis on behavioral and psychological symptoms.
- Psychosocial interventions and caregiver support are key to managing disease course. Caregiver support groups are beneficial to caregivers and should be considered, where available.
Quick Reference
History & Exam
Key Factors
memory loss
disorientation
nominal dysphasia
misplacing items/getting lost
apathy
decline in activities of daily living and instrumental activities of daily living (IADLs)
personality change
unremarkable initial physical exam
Other Factors
mood changes
poor abstract thinking
constructional dyspraxia
prosopagnosia
autoprosopagnosia
Diagnostics Tests
1st Tests to Order
bedside cognitive testing
CBC
metabolic panel
serum thyroid-stimulating hormone (TSH)
serum vitamin B12
urine drug screen
CT
MRI
Other Tests to consider
cerebrospinal fluid (CSF) analysis
serum rapid plasma reagin/Venereal Disease Research Laboratory (VDRL)
serum HIV
formal neuropsychological testing
genetic testing
fluorodeoxyglucose-PET (FDG-PET)
single-photon emission CT (SPECT)
electroencephalogram (EEG)
Emerging Tests
amyloid-PET
Treatment Options
ongoing
all patients
all patients
moderate to severe disease, or cholinesterase inhibitors contraindicated, not tolerated, or ineffective
Definition
Classifications
Diagnostic and Statistical Manual of Mental Disorders, 5th ed, text revision (DSM-5-TR) classification of major and mild neurocognitive disorders
- Alzheimer disease
- Frontotemporal degeneration
- Lewy body disease
- Vascular disease
- Traumatic brain injury
- Substance/medication use
- HIV infection
- Prion disease
- Parkinson disease
- Huntington disease
- Another medical condition
- Multiple etiologies
- Unknown etiology.
Vignette
Common Vignette 1
Common Vignette 2
Epidemiology
Etiology
Pathophysiology
Diagnostic Approach
History from patient and caregiver
Cognitive testing
Physical exam
Laboratory investigations
- Complete blood count
- Basic metabolic panel including liver function tests and serum calcium
- Thyroid-stimulating hormone
- Vitamin B12
- Urine drug screen (as appropriate)
- Serologic testing for syphilis (rapid plasma reagin/Venereal Disease Research Laboratory [VDRL]) in people at risk
- HIV testing in people at risk.
Other investigations
Imaging studies
Risk Factors
History & Exam
Tests
Differential Diagnosis
Delirium
Differentiating Signs/Symptoms
- Inattention and fluctuating level of consciousness.
- Disorientation common.
- Reversible causes may be present and should be corrected.
- Fluctuating course, worse at nighttime.
- Fragmentary, fleeting hallucinatory experiences; visual, tactile, or auditory in form.
Differentiating Tests
- The Confusion Assessment Method (CAM) screening tool is well validated in distinguishing dementia.
- Repeated Mini-Mental State Examination or CAM evaluations will show acute fluctuations over time.
Depression
Differentiating Signs/Symptoms
- Hallmark features are depressed mood and loss of interest/pleasure in usual activities.
- Memory loss is not the predominant or a common feature, although memory complaints are common in older people with depression.
- Depression may present acutely.
- Negative cognitions, preserved visuospatial function, and biologic symptoms may help differentiate.
Differentiating Tests
- Geriatric Depression Scale (long and short form), Hamilton Depression Scale, and Cornell Scale for Depression in Dementia may help differentiate.
- Limited or no changes on MRI scanning.
Vascular dementia
Differentiating Signs/Symptoms
- Deficits include memory loss, difficulty in problem solving, disinhibition, and focal neurologic deficits consistent with stroke location.
- Cardiovascular risk factors may be present.
- Further cognitive and functional decline usually occurs in a stepwise manner.
- Subcortical depression and apathy are common.
- Clinical history of temporally associated stroke symptoms supports this diagnosis.
- Sometimes coexists with AD (mixed dementia).
Differentiating Tests
- CT or MRI scanning demonstrates areas of past infarction and perivascular ischemia.
Dementia with Lewy bodies
Differentiating Signs/Symptoms
- Vivid visual hallucinations, Parkinson features (shuffling gait, bradykinesia, and falls), and cognitive fluctuations are characteristic.
- Rapid eye movement sleep disorder may be present.
- Progression of disease is more rapid than AD.
Differentiating Tests
- No reliable or valid differentiating test.
- Brain pathology demonstrates the presence of round, eosinophilic, intraneuronal inclusions called Lewy bodies. Neuropathologic findings include neurofibrillary tangles, amyloid plaques, and Lewy neurites.
Differentiating Signs/Symptoms
- Behavioral variant: impulsive, socially inappropriate behavior; marked apathy or inertia; loss of empathy; hyperorality; marked executive dysfunction.
- Personality change and behavioral disturbance occur early and are prominent features.
- Language variants may be progressive nonfluent aphasia, semantic dementia (word meaning), or logopenic (impaired word finding and difficulty with repetition).
- Onset often at the ages of 50 to 60 years, but may present at a younger age. Progresses more rapidly than AD.
Differentiating Tests
- CT or brain MRI reveals structural atrophy in the frontal and/or temporal lobes.
- Positron emission tomography or single-photon emission CT scanning shows reduced brain activity in the frontal and temporal lobes.
- Brain histology may reveal diagnostic findings (such as Pick bodies composed of tau protein, TDP-43 proteinopathy, or FUS proteinopathy).
Parkinson disease dementia
Differentiating Signs/Symptoms
- Features are similar to dementia with Lewy bodies and may include progressive cognitive decline and well-formed visual hallucinations in the context of established Parkinson disease.
- Motor symptoms include rigidity, resting tremor, bradykinesia, and postural instability preceding cognitive symptoms.
Differentiating Tests
- MRI usually reveals global brain atrophy in people with Parkinson disease.
Creutzfeld-Jacob disease (CJD)
Differentiating Signs/Symptoms
- Rapid decline in cognition or behavior over several months in sporadic form; longer in variant form.
- Prominent psychiatric/behavioral symptoms in variant form (early onset, found mainly in UK and Europe).
- Marked impairment in executive functioning. Early neurologic signs include startling myoclonus and paresthesias, progressing to incontinence of urine and feces, plus loss of speech.
Differentiating Tests
- Sporadic form: signal hyperintensity often present in the caudate nucleus and putamen on diffusion-weighted and fluid-attenuated inversion-recovery MRI. Cortical ribboning is also a common feature on these imaging sequences.
- Pulvinar sign in variant CJD (vCJD) is a common MRI finding.
- Tonsillar biopsy may be future diagnostic development in vCJD.
- Characteristic electroencephalogram (EEG) findings are triphasic periodic sharp wave complexes seen on repeated EEG testing as the illness progresses.
- Cerebrospinal fluid 14-3-3 protein assays may aid in diagnosis when the clinical suspicion is high.
Criteria
- Insidious onset
- Clear-cut history of worsening of cognition by report or observation, and
- The initial and most prominent cognitive deficits are evident on history and examination (amnestic versus nonamnestic presentation).The diagnosis of probable AD dementia should not be applied when there is evidence of (a) substantial concomitant cerebrovascular disease; or (b) core features of dementia with Lewy bodies; or (c) prominent features of behavioral variant frontotemporal dementia; or (d) prominent features of semantic variant primary progressive aphasia or nonfluent/agrammatic variant progressive aphasia; or (e) evidence for another concurrent, active neurological disease, or a non-neurological medical comorbidity, or use of medication that could have a substantial effect on cognition.
- Atypical course. Meets the core criteria in terms of the nature of the cognitive deficits for AD dementia, but either has a sudden onset of cognitive impairment or demonstrates insufficient historical detail or objective cognitive documentation of progressive decline.
- Etiologically mixed representation. Meets the core criteria for AD dementia but has evidence of (a) concomitant cerebrovascular disease; or (b) features of dementia with Lewy bodies other than dementia itself; or (c) evidence for another neurological disease or a non-neurological medical comorbidity or medication used that could have a substantial effect on cognition.
- The criteria are met for a major or mild neurocognitive disorder.
- Major neurocognitive disorder: evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains that interferes with independence in everyday activities. The cognitive deficits do not occur exclusively in the context of a delirium and are not better explained by another mental disorder.
- Specify severity:
- Mild: difficulties with instrumental activities of daily living (e.g., housework, managing money)
- Moderate: difficulties with basic activities of daily living (e.g., feeding, dressing)
- Severe: fully dependent.
- Specify:
- With agitation: if the cognitive disturbance is accompanied by clinically significant agitation
- With anxiety: if the cognitive disturbance is accompanied by clinically significant anxiety
- With mood symptoms: if the cognitive disturbance is accompanied by clinically significant mood symptoms (e.g., dysphoria, irritability, euphoria)
- With psychotic disturbance: if the cognitive disturbance is accompanied by delusions or hallucinations
- With other behavioral or psychological disturbance: if the cognitive disturbance is accompanied by other clinically significant behavioral or psychological disturbance (e.g., apathy, aggression, disinhibition, disruptive behaviors or vocalizations, sleep or appetite/eating disturbance)
- Without accompanying behavioral or psychological disturbance: if the cognitive disturbance is not accompanied by any clinically significant behavioral or psychological disturbance.
- Mild neurocognitive disorder: evidence of modest cognitive decline from a previous level of performance in one or more cognitive domains that does not interfere with independence in everyday activities. Greater effort, compensatory strategies, or accommodation may be required to preserve independence in complex instrumental activities of daily living (e.g., paying bills, managing medications). The cognitive deficits do not occur exclusively in the context of a delirium and are not better explained by another mental disorder.
- Specify:
- Without behavioral disturbance: if the cognitive disturbance is not accompanied by any clinically significant behavioral disturbance
- With behavioral disturbance (specify disturbance): if the cognitive disturbance is accompanied by a clinically significant behavioral disturbance (e.g., apathy, agitation, anxiety, mood symptoms, psychotic disturbance, or other behavioral symptoms).
- There is insidious onset and gradual progression of impairment in one or more cognitive domains (for major neurocognitive disorder, at least two domains must be impaired).
- Criteria are met for either probable or possible Alzheimer disease. For major neurocognitive disorder, probable Alzheimer disease is diagnosed if either of the following is present; otherwise, possible Alzheimer disease should be diagnosed.
- Evidence of a causative Alzheimer disease genetic mutation from family history or genetic testing.
- All three of the following are present:
- Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing).
- Steadily progressive, gradual decline in cognition, without extended plateaus.
- No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).
For mild neurocognitive disorder, probable Alzheimer disease is diagnosed if there is evidence of a causative Alzheimer disease genetic mutation from either genetic testing or family history. Possible Alzheimer disease is diagnosed if there is no evidence of a causative Alzheimer disease genetic mutation from either genetic testing or family history, and all three of the following are present:- Clear evidence of decline in memory and learning.
- Steadily progressive, gradual decline in cognition, without extended plateaus.
- No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely contributing to cognitive decline).
- The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.
- Progressive deficits in two or more areas of cognition, including memory
- Onset between the ages of 40-90 years
- Absence of systemic or other brain diseases capable of producing a dementia syndrome, including delirium.
Screening
Target population
Cognitive screening tests
Treatment Approach
Information and support
Environmental review
Cognitive impairment: pharmacotherapy goals
- Slow symptoms of disease progression by preserving memory and functional abilities
- Reduce behavioral disturbance
- Delay entry into institutional care settings.
- Cholinesterase inhibitors[111]
- N-methyl-D-aspartate (NMDA) receptor antagonists.
Cognitive impairment: cholinesterase inhibitors
Cognitive impairment: NMDA receptor antagonists
Cognitive impairment: nonpharmacologic treatments with limited evidence or no effectiveness
Cognitive impairment: pharmacologic treatments with limited evidence or no effectiveness
Behavioral and psychological symptoms of AD
- Anxiety
- Agitation
- Aggression
- Apathy
- Wandering
- Hallucinations
- Delusions
- Depression
- Insomnia
- Dementia-related psychosis.
Behavioral and psychological symptoms management: nonpharmacologic strategies
- Always explaining the caregiving actions in advance, such as putting clothes on or helping with showering
- Giving written instructions whenever possible
- Ensuring that comorbid illnesses are appropriately addressed by physician and nursing staff
- Ensuring that pain is adequately addressed
- Using calendars, clocks, and charts to help patients stay oriented to the time and place
- Using lighting to reduce confusion and restlessness at night time
- Ensuring the environment is safe and removing unnecessary furniture and items that might harm patients if they wander.
Behavioral and psychological symptoms management: pharmacologic treatment
- Reduce symptom severity
- Improve the quality of life of the patient
- Reduce caregiver stress.
- All behavioral and psychosocial strategies should be exhausted first.[188]
- Cognition and orientation should be monitored assiduously.
- Risks should be discussed with caregivers and a decision made in collaboration with them.
- Particular care should be used in institutional settings; dose increases can inadvertently occur, without adequate awareness of the risks, due to difficulties in managing challenging behaviors.
- Treatment should be stopped if there is evidence of neurologic symptoms, increased confusion, or decline in mobility. In addition, monitoring for cardiac and metabolic side effects should be used appropriately.
- Patients should be monitored for metabolic and cardiovascular side effects (e.g., ECGs, hemoglobin A1c).
- Patients should be frequently assessed for efficacy of the intervention, and periodically for the need for ongoing treatment.[187]
Treatment Options
all patients
supportive treatment
Comments
- It is important to provide education, support, and resources to the patient and the family.[103] Discussion of advanced directives and end-of-life care that may be anticipated should take place at an early stage, and needs to be handled sensitively, based on a good patient-provider and family-provider relationship.[103] [105] [106]
- Caregiver support is crucial to management of AD. A mental health professional should be made available to provide input. A referral should be made to a community service organization, such as the Alzheimer's Association.Alzheimer's Association National Institute on Aging: about Alzheimer's disease - caregiving MedlinePlus: Alzheimer's caregivers Family Caregiver Alliance resource center
- Simple measures can help modulate behaviors such as agitation, delusions, and hallucinations. Actions that can be useful include:
- Always explaining the caregiving actions in advance, such as putting clothes on or helping with showering
- Giving written instructions whenever possible
- Ensuring that comorbid illnesses are appropriately addressed by physician and nursing staff
- Ensuring that pain is adequately addressed
- Using calendars, clocks, and charts to help patients stay oriented to the time and place
- Using lighting to reduce confusion and restlessness at night time
- Ensuring the environment is safe and removing unnecessary furniture and items that might harm patients if they wander.
- Communication strategies that may foster improved communication between patients with AD and caregivers include: using short and simple sentences, explaining things, decreasing distractions, asking close-ended questions or providing response choices, and not pushing the patient to come up with a word, name, or memory.[191]
- Late-/end-stage care includes palliative measures, end-of-life choices, and discussing goals of care with the family.[103] [105] These issues are summarized in information on end-of-life planning from the Alzheimer's Association.Alzheimer's Association: end-of-life planning
environmental control measures
Comments
- Measures such as identification bracelets or installing sound and motion detectors make the environment safe for wandering patients and reduce the burden on caregivers. Tagging with devices with global positioning technology has also been proposed and may offer some reassurance to caregivers about the patient's safety.Alzheimer's Society: assistive technology
cholinesterase inhibitor
Primary Options
- donepezil
mild to moderate disease: 5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day; moderate to severe disease: 5 mg orally once daily initially, increase gradually according to response, maximum 23 mg/day
- donepezil
- rivastigmine
1.5 mg orally twice daily initially, increase gradually according to response, maximum 12 mg/day
- rivastigmine
- rivastigmine transdermal
4.6 mg/24 hour patch once daily initially, increase gradually according to response, maximum 13.3 mg/24 hour patch once daily
- rivastigmine transdermal
- galantamine
4 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 24 mg/day; 8 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 24 mg/day
- galantamine
Comments
- Treatment should be started when the diagnosis of mild AD is made.
- Oral rivastigmine and oral galantamine are approved by the Food and Drug Administration (FDA) for mild to moderate AD.
- Oral donepezil and transdermal rivastigmine are FDA-approved for mild to severe AD.[118]
- A once-daily extended-release formulation of galantamine is also available and should be considered when compliance or dosing rationalization is an issue.[117]
- Donepezil has been shown to be beneficial at all stages of the disease.[119] Adverse effects, particularly gastrointestinal, are significantly more common with the higher-dose formulation approved for moderate to severe disease.[120] Increasing the dose to the high end of the dose range may confer only modest benefit.
- The rivastigmine transdermal patch may increase compliance and reduce cholinergic adverse effects, and is preferred by caregivers to oral formulations.[121] [122] [123] [124] [125] Patients experiencing adverse effects with oral cholinesterase inhibitors may be transitioned to transdermal rivastigmine therapy without significant complications.[126]
- The clinical benefit of cholinesterase inhibitors is modest.[111] Open-label extensions suggest that benefits may continue beyond 1 year with ongoing treatment.[114] [115] However, retrospective data from the UK indicate that cholinesterase inhibitors are associated with a period of cognitive stabilization (2 to 5 months) before a continued decline in cognitive function at the pretreatment rate.[129]
- Cholinesterase inhibitors should be started at the lowest possible dose and titrated gradually. This is particularly relevant in older patients, who are more sensitive to cholinergic adverse effects, and in those in whom comorbidity may be exacerbated by altered acetylcholine metabolism. Renal impairment and hepatic dysfunction can also affect dosing.
- Cholinesterase inhibitors should not be stopped abruptly, as patients may experience rebound worsening of cognition. There is little consensus about when to consider discontinuation of these treatments, and what criteria to use.[116]
management of depression
Primary Options
- sertraline
50-200 mg orally once daily
- sertraline
- citalopram
<60 years of age: 20-40 mg orally once daily; ≥60 years of age: 10-20mg orally once
- citalopram
- escitalopram
10-20 mg orally once daily
- escitalopram
Secondary Options
- mirtazapine
15-45 mg orally once daily
- mirtazapine
Comments
- Depression is very common in people with AD and significantly impacts cognitive function, as well as increasing caregiver stress.
- Nonpharmacologic strategies have some evidence of benefit for patients with dementia: some functional benefits of an exercise and educational program in depression management have been reported.[160] Psychological interventions (e.g., cognitive behavioral therapy, interpersonal therapies) and music therapy may reduce symptoms of anxiety in people with mild dementia.[145] [162]
- Clinical practice includes a trial of an antidepressant, particularly a selective serotonin-reuptake inhibitor (SSRI) (alongside consideration of nonpharmacologic interventions), and monitoring closely for efficacy, as it is not clear who will benefit.[168] Time-limited trials (i.e., 3-6 months) and careful monitoring of adverse effects and efficacy (e.g., using the Geriatric Depression Scale or the Cornell Scale for Depression in Dementia) are recommended.
- Sertraline, citalopram, and escitalopram are preferred; SSRIs with a longer half-life (i.e., fluoxetine), those with increased potential for drug-drug interactions mediated by cytochrome P450 (fluoxetine, paroxetine, fluvoxamine), or those known to be more activating (e.g., paroxetine) should be used with caution.
- Mirtazapine, an atypical antidepressant, is an appropriate treatment when poor appetite and insomnia are present.
- Use of serotonin-norepinephrine reuptake inhibitors may be considered depending on patient preference, comorbidity, and clinician experience.
- Doses should be started low and increased gradually according to response. Medications should be titrated to effect over 1-2 months until target dose is reached.
management of dementia-related psychosis
Primary Options
- risperidone
0.25 mg orally once or twice daily initially, increase gradually according to response, maximum 2 mg/day
- risperidone
- olanzapine
2.5 mg orally once daily initially, increase gradually according to response, maximum 5 mg/day
- olanzapine
- quetiapine
25 mg orally (immediate-release) once or twice daily initially, increase gradually according to response, maximum 150 mg/day
- quetiapine
- aripiprazole
2-5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day
- aripiprazole
Secondary Options
- haloperidol
0.25 to 0.5 mg orally once or twice daily initially, increase gradually according to response, maximum 2 mg/day
- haloperidol
- ziprasidone
consult specialist for guidance on dose
- ziprasidone
Comments
- Antipsychotic use in people with AD is controversial.[181] [182] [192] The Food and Drug Administration has issued black box warnings for all atypical and typical antipsychotics in relation to dementia-related psychosis, as they have been shown to increase mortality.[181] [182] [193] However, in cases of severe agitation or danger to self or others, antipsychotics have shown some benefit in management.
- All antipsychotics have the potential to cause extrapyramidal symptoms, but these adverse effects are less common with atypical antipsychotics than with conventional (typical) antipsychotics.[185] One systematic review and meta-analysis concluded that atypical antipsychotics (and cholinesterase inhibitors) may improve neuropsychiatric symptoms in patients with AD, but should be used with caution.[186]
- If there is evidence of vascular dementia, antipsychotics should be used with extra caution and monitoring for cardiovascular adverse effects, because of the reported association with an increased incidence of stroke and cardiovascular events.
- The American Psychiatric Association guidelines recommend reserving antipsychotic medication for symptoms that are considered severe, dangerous, and/or cause significant distress, and assessing efficacy and side effects to continuously balance the risk/benefit ratio in each individual patient.[187] Modifiable factors, such as pain, should be addressed prior to instituting therapy.
- Low doses of antipsychotics may be prescribed cautiously in patients with neuropsychiatric symptoms.
management of insomnia
Primary Options
- trazodone
25-50 mg orally once daily at bedtime initially, increase gradually according to response, maximum 100-200 mg/day
- trazodone
Comments
management of other behavioral and psychological symptoms
Primary Options
- citalopram
10 mg orally once daily initially, increase gradually according to response, maximum 30 mg/day
- citalopram
- carbamazepine
50 mg orally (regular-release tablets) twice daily initially, increase gradually according to response, maximum 200-400 mg/day
- carbamazepine
- trazodone
50 mg orally two to three times daily initially, increase gradually according to response, maximum 400 mg/day (outpatient) or 600 mg/day (inpatient)
- trazodone
Comments
- Aggression and agitation have multiple causes in people with AD. Symptoms may stem from comorbid depression, adverse effects of medication, worsening medical conditions, pain, or delirium confusion with complex tasks. The first task of the clinician is to rule out an underlying medical cause for the symptoms.
- Nonpharmacologic strategies may help to lessen anxiety and agitation, as well as improving caregiver confidence and reducing caregiver distress.[163] [164] Simple measures such as providing a comfortable environment and encouraging social gatherings help patients adjust to their surroundings and lessen anxiety and agitation. Activities such as gardening, vacuuming, and setting the table provide routine and foster a sense of utility.
- Selective serotonin-reuptake inhibitors (SSRIs) reduce symptoms of agitation compared with placebo in people with dementia.[174] Data from one randomized controlled trial suggest that citalopram reduces agitation, irritability, anxiety, delusions, and caregiver distress.[175] [176] Patients with milder cognitive impairment and moderate agitation were more likely to respond to citalopram.[177] Monitoring for cardiac side effects, such as prolonged QT interval, is important. Patients who are already taking an SSRI for depression should not be started on citalopram for behavioral or psychological symptoms because of the risk of serotonin syndrome.
- There is some evidence that carbamazepine is effective for the management of agitation and aggression in dementia, although tolerability may be an issue.[178]
- Existing medications such as benzodiazepines or antipsychotics can cause paradoxical agitation or akathisia and may need to be reduced or stopped altogether.
moderate to severe disease, or cholinesterase inhibitors contraindicated, not tolerated, or ineffective
switch to or add memantine
Primary Options
- memantine
5 mg orally (immediate-release) once daily initially, increase gradually according to response, maximum 20 mg/day given in 2 divided doses; 7 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 28 mg/day
- memantine
Comments
- Co-administration of memantine with a cholinesterase inhibitor may be considered as the range of AD symptoms increases and the severity of behavioral and psychological symptoms worsens. Meta-analyses suggest that adding memantine to a cholinesterase inhibitor may modestly improve cognition in people with moderate to severe AD.[130] [134] [135] These drugs may be available in proprietary combination formulations in some countries.
- Memantine should be given as a sole treatment if cholinesterase inhibitors are contraindicated, are not tolerated, or have been shown to be ineffective.[131]
Emerging Tx
Aducanumab
Lecanemab
Donanemab
Prevention
Primary Prevention
- Medication (antihypertensives, statins, nonsteroidal anti-inflammatory drugs, aspirin, antidiabetic drugs, or cholinesterase inhibitors)
- Over-the-counter supplements (omega-3 fatty acids, ginkgo biloba, B vitamins, vitamin D with calcium, beta-carotene, or multivitamins)
- Cognitive training.
Follow-Up Overview
Prognosis
- Medication administration
- Household chores
- Daily transport
- Financial matters
- Other activities of daily living.
Monitoring
Complications
Citations
GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 Jan;18(1):88-106.[Abstract][Full Text]
Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020 Aug 8;396(10248):413-46.[Abstract][Full Text]
Fink HA, Linskens EJ, Silverman PC, et al. Accuracy of biomarker testing for neuropathologically defined Alzheimer disease in older adults with dementia. Ann Intern Med. 2020 May 19;172(10):669-77.[Abstract]
O'Brien JT, Holmes C, Jones M, et al. Clinical practice with anti-dementia drugs: a revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. 2017 Feb;31(2):147-68.[Abstract][Full Text]
Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2018 Jun 18;(6):CD001190.[Abstract][Full Text]
Birks JS, Chong LY, Grimley Evans J. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2015 Sep 22;(9):CD001191.[Abstract][Full Text]
McShane R, Westby MJ, Roberts E, et al. Memantine for dementia. Cochrane Database Syst Rev. 2019 Mar 20;(3):CD003154.[Abstract][Full Text]
- BMJ talk medicine podcast: Alzheimer's dementia
- Alzheimer's Association: 10 early signs and symptoms of Alzheimer's
- Saint Louis University School of Medicine: SLUMS Examination
- Alzheimer's Association: Mini-Cog(TM)
- Montreal Cognitive Assessment
- Alzheimer's Association
- National Institute on Aging: about Alzheimer's disease - caregiving
- MedlinePlus: Alzheimer's caregivers
- Family Caregiver Alliance resource center
- Alzheimer's Society: assistive technology
- Alzheimer's Association: end-of-life planning
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Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
Practice parameter for both fluorodeoxyglucose (FDG) and amyloid brain positron emission tomography (PET) or PET/computed tomography (CT) for patients with cognitive decline.Published by
American College of Radiology (ACR); American College of Nuclear Medicine (ACNM); American Society for Neuroradiology (ASNR); Society of Nuclear Medicine and Molecular Imaging (SNMMI)
Published
2020
Summary
Evidence-based recommendations on structural imaging for evaluating patients with dementia.Published by
American College of Radiology
Published
2019
Summary
Evidence-based recommendations regarding structural and functional brain imaging for the diagnosis of dementia.Published by
British Association for Psychopharmacology
Published
2017
Summary
Evidence-based recommendations and consensus-based good practice points on the use of neuropsychologic assessment, structural and functional imaging, electroencephalography, cerebrospinal fluid analysis, and other investigations in the diagnosis of AD.Published by
European Academy of Neurology (European Federation of Neurological Societies)
Published
2010
Summary
Evidence-based recommendations on genetic testing in patients with early-onset AD.Published by
European Academy of Neurology (European Federation of Neurological Societies)
Published
2010
Treatment
Summary
Guidance on neuropalliative care focusing on specific needs of patients with neurologic illness and their families, with the aim of helping patients to have the best quality of life for as long as possible.Published by
American Academy of Neurology
Published
2022
Summary
Summary of ethical considerations that often arise when caring for patients with dementia.Published by
American Academy of Neurology
Published
2021
Summary
Evidence-based recommendations on the use of antipsychotics in people with dementia.Published by
American Psychiatric Association
Published
2016
Summary
Includes pharmacologic treatment considerations for patients with AD, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia.Published by
World Federation of Societies of Biological Psychiatry
Published
2011
Summary
Practice recommendations for physicians and other medical care providers who work with people living with dementia and their families in residential and community-based care settings.Published by
Alzheimer's Association
Published
2018
Summary
Addresses the assessment, treatment, patient and family education and support, and legal considerations associated with AD, including early stage and end-of-life issues.Published by
California Department of Public Health
Published
2017
Summary
Recommendations from an expert international consensus panel.Published by
International Psychogeriatric Association
Published
2019
Summary
Recommendations regarding the pharmacologic management of AD.Published by
European Academy of Neurology (European Federation of Neurological Societies); European Academy of Neurology
Published
2015
Summary
Evidence-based recommendations and consensus-based good practice points on the management of AD, including pharmacologic and nonpharmacologic therapies for cognitive impairment and for behavioral and psychological symptoms.Published by
European Academy of Neurology (European Federation of Neurological Societies)
Published
2010
Summary
Includes recommendations for the pharmacologic treatment of AD.Published by
British Association for Psychopharmacology
Published
2017