Alzheimer disease (AD) accounts for almost 80% of all dementia diagnoses.1 Currently, more than 5 million Americans suffer from this debilitating illness, with the highest prevalence in the oldest age groups. The most significant risk factor in the development of AD is increasing age.2,3 As the number of older Americans increases, the incidence of AD will invariably rise. By 2050, with every 33 seconds, one American will develop the illness.1
AD is a progressive disease, and its trajectory is characterized by cognitive and functional decline. As such, it creates a toll not only on patients but also on their families and friends. There are no measures that have demonstrated effectiveness in preventing the onset of AD; however, when diagnosed early and managed appropriately, cognitive function may be extended.4 By virtue of being primary care providers (PCPs), NPs have a key role in early diagnosis and management of AD, as well as supporting the patient's caregivers.5
AD is characterized by neurofibrillary tangles, and beta-amyloid plaques, which damage nerve cells (see Tissue changes in AD). The presence of these can lead to neuronal (cholinergic and glutamatergic) cell destruction.6,7 Collectively, this destruction creates synaptic neurotransmitter imbalances, with reduced levels of acetylcholine and high levels of glutamate, which can be neurotoxic.
The degree of acetylcholine deficiency is directly correlated to the learning and memory deficits of patients with AD.6 Excessive stimulation of glutamate receptors in the synapses produces high levels of glutamate. It is speculated that this destruction also impairs learning and memory, and is positively correlated with the memory loss and cognitive decline that are the hallmark characteristics of AD.
Early detection and diagnosis is essential to initiate treatment and slow the progression of the disease.8 In an effort to optimize the early identification and treatment of the illness, the criteria and guidelines for the clinical diagnosis of AD were updated in April 2011 by a workgroup charged by the National Institute on Aging (NIA) and the Alzheimer's Association.9
The salient differences from the original criteria include the establishment of 3 stages of AD:
* Mild cognitive impairment due to AD
* Dementia due to AD; and a preliminary framework for biomarker testing.9–11
The preclinical stage of AD occurs before clinical symptoms (e.g. memory loss) manifest and before daily activities have been affected. The stage is characterized by changes in biomarkers (e.g. beta-amyloid protein) which indicate a measurable, early disease-state. Although the use of biomarkers is identified, diagnostic criteria related to biomarkers have not been determined. Therefore, immediate preclinical diagnosis is not recommended until further research on the clinical utility of biomarkers is well established.12
Mild cognitive impairment (MCI) from AD represents mild changes in cognitive abilities and memory which are noticeable to the person, as well as to family members and friends. The impairments are measureable, but are not severe enough to interfere with daily life. Many, but not all patients with MCI will progress to a diagnosis of AD dementia. Episodic memory impairment (e.g. learning new information) is often seen in those who do progress in this stage.10
The diagnosis of AD dementia encompasses varying degrees of illness severity and is present when cognitive or behavioral symptoms result in a loss of function in usual activities.11 It also represents a decline from previous levels of performance; and cannot be explained by delirium or other major mental health disorders.
Cognitive impairment is diagnosed by a combination of history-taking (from patient and reliable informant) and an objective assessment (using "bedside" mental status examination or neuropsychiatric testing). Formal neuropsychiatric testing is not required for diagnosis, but should be used if the results of the routine history and bedside mental status evaluation are inconclusive.11
AD dementia can be further classified clinically as: 1) Probable AD dementia or 2) Possible AD dementia (see Core clinical criteria of Alzheimer's dementia).11
The criteria for probable AD is largely related to the exclusion of other causes of dementia. NPs should be alert for other causes of cognitive impairment that can be mistaken for AD such as vascular dementia, Parkinson's disease, Lewy body dementia, delirium, and depression (see Clinical features of AD and other selected diagnoses).15 Depression in elderly patients can also impair executive function in a manner similar to that of AD; although AD and depression can coexist. In some cases, depression precedes clinical symptoms of AD.15
If neuropsychiatric symptoms appear acutely, NPs should investigate the possibility of reversible etiologies such as infection, dehydration, an adverse drug reaction, or even uncontrolled pain.
The standard workup for diagnosing AD includes a physical exam, informal and/or neuropsychological tests, lab tests, and imaging studies. Laboratory studies (serum vitamin B12 levels, thyroid function tests) are necessary to rule out secondary causes. CT and MRI studies can exclude alternative causes such as subdural hematoma or brain tumor. Neuroimaging can detect cerebrovascular disease, suggesting vascular or mixed dementia.18
Once the diagnosis of AD dementia is confirmed, the patient and family should be informed.5 Despite the anxiety, stress, and depression that a diagnosis of AD may bring, patients and family caregivers normally prefer open disclosure and discussion of the disease with their PCPs.19
Goals of treatment
Treatment goals are directed toward cognitive and noncognitive symptom management, as well as the needs of family caregivers. Optimizing and preserving the patient's functional abilities, quality of life, and independence are important. Additional goals include individualized treatment and minimizing adverse effects, and keeping caregiver burden/strain to a minimum through education about the disease, realistic expectations of treatment, and the availability of community services.6 Treatment plans include pharmacotherapy for cognitive decline, management of accompanying noncognitive symptoms of the disease, and alternative treatment modalities (e.g. pet therapy).
Prior to starting treatment, all reversible causes of cognitive dysfunction must be eliminated. Clinical baselines using validated instruments are necessary to monitor treatment responses (e.g. KATZ Activities of Daily Living scale, Instrumental Activities of Daily Living scale, Mini-Mental State Examination (MMSE), and the Mini-Nutritional Assessment scale.20,21,22,23 The Clinical Dementia Rating (CDR) may be helpful to measure functional capacity.24
Pharmacotherapy for cognitive decline
No drugs have demonstrated effectiveness in halting the AD process. To slow the progression of cognitive decline, acetylcholinesterase inhibitors (ACIs) are considered first-line. ACIs include donepezil (Aricept, Aricept ODT), galantamine (Razadyne, Razadyne ER), rivastigmine (Exelon, Exelon Patch), and tacrine (Cognex). They are used for mild-to-moderate AD in order to prevent the degradation and destruction of acetylcholine, which helps to elevate synaptic levels of the neurotransmitter.
In 2010, donezepil was FDA-approved for moderate-to-severe AD based on clinical trials.13 Of this class, donepezil is considered first-line therapy because of its once-daily dosing, narrower adverse effect profile, and efficacy. Tacrine, although available, is rarely used in clinical practice due its inconvenient dosing schedule (four times daily) and risk of hepatotoxicity.14
Drug interactions are common with ACIs. Use of ACIs with antipsychotics can increase risk of Parkinson-like symptoms; and the use of ACIs in combination with antiarrhythmic drugs, beta-blockers, or digoxin can cause bradycardia or other changes in heart rate or conduction.25,26 ACIs can also increase gastric secretion, therefore increasing the risk of ulcer development in patients taking NSAIDs.25
Additional adverse effects associated with ACIs include nausea, vomiting, anorexia, and diarrhea; much of which are self-limiting or can be minimized by slow drug titration.
Memantine (Namenda), can be used as stand-alone symptomatic therapy or combined with an ACI to treat moderate-to-severe AD.6,27 Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, reduces high levels of neurotoxic glutamate by suppressing glutamatergic activity. The drug is excreted renally; therefore patients with chronic kidney disease or diminished renal function may require a lower starting dose and should be closely monitored.26
Pharmacotherapy for noncognitive (neuropsychiatric) symptoms
The most frequent noncognitive symptoms in AD are agitation, anxiety, depression, sleep disturbance, and psychosis.6 These symptoms have been associated with morbidity, mortality, and increased healthcare costs for those who suffer with dementia.25 Pharmacologic management targets specific behaviors, but is not benign intervention. Treatments should be individualized and should follow careful consideration of the patient's needs.6,25
Antipsychotics are used to treat the neuropsychiatric symptoms (such as agitation, delusions, and aggression) associated with AD.28 When selecting an antipsychotic, concerns that need to be addressed include the risk of anticholinergic adverse effects, as well as drug cost.
In 2005, the FDA required drug manufacturers to issue a "black box" warning about the risk of increased mortality in the elderly being treated with second-generation antipsychotics (also known as atypical antipsychotics) for behavioral symptoms of dementia.29 Three years later, this warning was extended to include the use of typical or first-generation anitpsychotics as well. However, antipsychotics are still prescribed at low doses to manage behavioral symptoms, which is considered "off-label" use.4,29 The black-box warning does not mean the drugs have contraindications, and discussions of risk-benefit and potential adverse reactions with caregivers and patients prior to initiating treatment are crucial.4
Among the first-generation antipsychotics, haloperidol (Haldol) is associated with fewer anticholinergic effects. Extrapyramidal symptoms (EPS) are common in this drug class and can be particularly distressing to patients and families (see Common extrapyramidal symptoms).30,31
EPS can develop within days of initiating treatment, as well as at any time throughout the course of therapy. Patients should be monitored regularly for EPS; and, if present, cessation of treatment should be considered.31
The second-generation antipsychotics have fewer incidences of EPS; however, their high cost creates a barrier for some patients.6 Studies have suggested that although commonly used, some pharmacologic treatments for the behavioral symptoms of AD are ineffective. Of these medications, the efficacy of second-generation antipsychotics has the strongest supporting evidence.32
Benzodiazepine use in the management of episodic agitation or anxiety can be effective if agents with shorter half-lives are used (such as lorazepam [Ativan]). These drugs, however, are generally contraindicated due the risk of falls, delirium, disinhibition, and risk for addiction.6,33
Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are considered first-line therapy in the treatment of depression because they have fewer adverse effects than tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs). If patients experience anxiety, then paroxetine (Paxil) can be used, which has a greater sedative effect. In addition to its antidepressant effect, citalopram (Celexa) has been shown to improve certain emotional symptoms of AD including panic, bluntness, irritability, and restlessness.6 Recommended target doses for older adults are lower than those in younger populations because of the decrease in metabolism related to aging.34
SSRIs are highly protein bound and inhibit several P-450 hepatic cytochrome isoenzymes, resulting in potential drug interactions. Concurrent use of antipsychotics may require a downward dose adjustment of the SSRI.34 Citalopram is less highly protein bound, thereby reducing the potential for drug interactions.35
There is ongoing debate regarding continuing the pharmacologic treatment of AD in its final stages; however, ACIs and NMDA-receptor antagonists are often continued. In randomized, placebo-controlled trials, donepezil and memantine showed statistically significant clinical benefit in moderate-to-severe stages of the disease compared with those who received placebo.36
Nonpharmacologic approaches for noncognitive symptoms
Nonpharmacologic approaches to address the behavioral symptoms of AD can be beneficial, and are ideal when combined with pharmacotherapy. Behavioral symptoms are a troubling part of the disease; and if present may indicate that emotional or biological needs are unmet.37
Patients with AD are sensitive to environmental stimuli and are easily agitated. The optimal environment is familiar, calm, well-lit, and well-heated. An unstable social environment can also affect behavioral symptoms of the illness. If left alone for long periods in unfamiliar places, agitation may result. Creating a more familiar environment through the use of pictures or objects from home may stimulate a remote feeling of comfort and alleviate the symptoms.37
Other treatments such as music, aromatherapy, or animal-assisted therapy (pet therapy) may also provide some benefit in the management of agitation.37,38,39 Music can create a neutral environment and override sounds that may cause overstimulation. If the patient is already overstimulated, music therapy should be used cautiously as it could result in additional patient stimulation. Special care should be taken when choosing music: it should be soothing, acceptable, and personalized to the patient (not simply what is immediately available).
Because PCPs frequently handle follow-up care, NPs can provide support and education for AD patients and their family caregivers.26 No consensus has been established on how often PCPs should follow up with patients with AD.5 As a general rule, follow-up must be tailored to the needs of each patient.
During office visits, conditions that may potentially lead to delirious episodes (delirium superimposed on dementia) such as dehydration or infection need to be assessed, as delirium occurrences are associated with a more rapid cognitive decline.40 The incidence of depression among AD patients is high; therefore it is recommended that depression screening also be a routine part of follow-up visits.41 Identification and management of comorbidities, as well as the evaluation of functional, cognitive, and nutritional status of patients is crucial.
With sensitivity and respect for continued mobility, NPs must also advise driving cessation when impairments jeopardize the safety of the patient and the public.42 In a systematic review, it was shown that drivers with AD at a severity of 1 using the CDR scale (roughly equivalent to a MMSE of less than 25 but greater than 19) were found to pose a significant traffic safety problem from crashes and from driving performance measurements.43 If practitioners advocate to cease driving, the transportation needs of patients with AD need to be addressed.
Although the rate of disease progression is variable, the natural course of the disease carries a predictable pattern. Initial progressive memory loss converts, over months and years, to disorientation, personality and judgment dysfunction, speech abnormalities, and apraxias.2 Patients also may suffer from impairment in visuospatial skills and executive functions. In general, the life expectancy of patients with AD will depend on the age at diagnosis. The median lifespan is about 7 to 10 years for those diagnosed in their 60s and early 70s; about 3 years or fewer for patients diagnosed in their 90s.44
Despite all available therapy, AD is absolutely progressive. The ability to care for oneself is lost over time. With aggressive management, AD patients often live out their final months—sometimes years—bed-ridden in a vegetative state.2
Patient and caregiver support
Follow-up patient visits also provide an opportunity to determine the general well-being of the caregiver. Physical and emotional exhaustion can be common occurrences.45 The demanding nature of caring for a person with AD is heightened as the disease progresses.46 Caregivers who indicate greater emotional stress and feelings of being "trapped" in care responsibilities are more likely to support institutionalization of their loved ones with AD.47 The most validated tool for assessing caregiver burnout is the "Zarit Burden Interview," where caregivers answer 22 questions about quality of life, financial issues, and emotional issues; and are scored on a scale of 0 to 4. A higher score reflects a higher burden placed on the caregiver.48
It is important for NPs to provide basic education about the course of illness, and certain legal issues such as an advance directive for healthcare, which includes a living will and designation of the "person of trust" or the power of attorney for healthcare, as these allow patients and their families to prepare ahead.5 NPs should also be alert for signs and symptoms of elder abuse in their patients, whether emotional, financial, or physical; which can be prevalent in this population.49
Despite the existence of many community services for AD patients and their caregivers, PCPs still do not access them enough.50 Because dementia care relies on developing sustained support to family and caregivers within the community, NPs need to be aware of all relevant support groups in the local area and communicate that information to caregivers (see Patient and family resources for a listing of national organizations).
AD is the most prevalent form of dementia in the elderly and is extremely challenging for both patients and families. Early intervention and appropriate use of supportive care by the NP can help with the cognitive and behavioral symptoms of the illness. NPs should work closely with family caregivers, providing education and referrals when necessary to ensure the health and safety of their patients.
Patient and family resources
A global voluntary health organization in Alzheimer care and support and the largest private, nonprofit funder of Alzheimer research.
Alzheimer's Foundation of America
Provides optimal care and services to individuals confronting dementia, and to their caregivers and families—through member organizations dedicated to improving quality of life.
Alzheimer's Disease Education and Referral Center
This is an up-to-date, comprehensive Alzheimer's disease information and resources from the National Institute on Aging (NIA).
National Family Caregivers Association
This organization educates, supports, empowers, and speaks up for the more than 65 million Americans who care for loved ones with a chronic illness or disability or the frailties of old age.
Family Caregiver Alliance
The first community-based nonprofit organization in the country to address the needs of families and friends providing long-term care at home.
National Alliance for Caregiving
Nonprofit coalition of national organizations focused on issues of family caregiving.
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