Alzheimer's Disease: Diagnosis, Treatment, and Research for RNs and LPNs Nursing CE Course

iated with dementia. Heavy alcohol consumption (more than four drinks for men or three drinks for women daily) is associated with an increased risk of AD, especially when combined with smoking. Mild to moderate alcohol intake, especially of red wine, may lower the risk or ameliorate progression. Social interaction with others and mental stimulation increase gamma oscillations in the brain and may work to prevent the development of AD (Alzheimer’s Association, 2019; Edwards et al., 2019; Pandya, 2018). Prospective studies dating back to 2003 indicate that regular physically, mentally, or socially stimulating leisure activities reduces the risk of dementia in older adults, as well as the presence of a rich social network as evidenced by social connections or support (Marseglia et al., 2019).

Initial Screening, Diagnosis, and Staging

Despite some recent advances in neuroimaging and the detection of some biomarkers (such as beta-amyloid and tau), the diagnosis of AD is still fundamentally clinical (Moore et al., 2014). Last revised in 2011 by a joint workgroup from the NIA and the Alzheimer’s Association, the diagnostic criteria for AD describes three stages of the disease. In the preclinical stage, there are no evident symptoms, but only underlying brain changes not yet detectable. This stage is an experimental concept only at this time, with the hope that imaging and biomarker studies will continue to progress and eventually lead to a profile that will identify individuals most likely to develop symptoms of AD. The second stage is marked by mild cognitive impairment (MCI), which includes symptoms of memory loss or thinking problems that are greater than expected given the individual’s age and education level, but not yet interfering with their ability to function independently. It requires concern about a change in cognition compared to previous and impairment of one or more cognitive functions, but preserved ability to function independently in daily life and the absence of dementia (NIA, n.d.).  Early dementia is defined by some as more substantial interference in daily function secondary to poor performance in more than one cognitive domain (Panegyres et al., 2016). Finally, the third stage is Alzheimer’s dementia. This stage is characterized by memory loss, word-finding difficulty, and/or visuospatial problems that are significant enough to impair the person’s ability to function independently. Not all people with MCI progress to Alzheimer’s dementia. Dementia due to AD must involve a minimum of two of the following domains: ability to acquire/retain new information, reasoning/judgement/handling of complex tasks, visuospatial abilities, language functions, or changes in personality/behavior. The 2011 NIA/Alzheimer’s Association guidelines also define the terms possible AD (when the criteria for AD are met, but the disease follows an atypical course or there is evidence of a mixed presentation) and probable AD (when all of the diagnostic criteria for AD are met, with gradual onset over months/years). Proven AD occurs only after a positive autopsy (NIA, n.d.). In 2013, the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) recognized that memory impairment may not be the first cognitive domain to be impaired, indicating mild neurocognitive disorder which closely resembles MCI but with less impairment in daily functioning (Panegyres et al., 2016).

Differential diagnoses such as depression, delirium, medication-related adverse effects, and thyroid dysfunction can often be ruled out with a complete history and physical exam, which should include a thorough neurological exam. This would help identify delirium (onset over days/weeks, not months/years) and any medication that might be contributing to the cognitive decline. Medications at increased risk for causing symptoms of cognitive impairment include opioids, anticholinergic medications, tricyclic antidepressants, benzodiazepines and other hypnotics, muscle relaxants, antihistamines, and antiepileptics. Standard laboratory tests recommended by the NAMCP and the Alzheimer’s Association should include thyroid stimulating hormone (TSH), complete blood count (CBC), vitamin B12 and folate levels, complete metabolic panel, fasting glucose, and tests for HIV and/or syphilis. Medication levels of potentially toxic medications such as digoxin (Lanoxin) and antiepileptics should be checked if appropriate. Imaging studies may be helpful in younger patients or those with a history of head trauma or focal symptoms to rule out stroke, tumor, hematoma, or hydrocephalus (Cordell et al., 2013; Pandya, 2018; Panegyres et al., 2016).

In 2014, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4) published their findings regarding the diagnostic criteria and treatment essentials for PCPs. They cautioned against neuroimaging all patients presenting with cognitive impairment but did recommend computed tomography (CT scan) or magnetic resonance imaging (MRI) for patients if the unexpected presence of cerebrovascular disease would change treatment. The CCCDTD4 explicitly recommends against routine use of positron emission tomography (PET) metabolic amyloid imaging, functional MRIs, and/or magnetic resonance spectroscopy except in research settings where appropriate (Moore et al., 2014).

Initial Screening

In 2013, the Alzheimer’s Association published recommendations for primary care providers (PCPs) to better detect cognitive decline as a regular component of the Medicare annual wellness visit (AWV), one of the new benefits included in the 2010 Affordable Care Act. The AWV includes detection of any cognitive impairment as one of its seven components, but the Centers for Medicare and Medicaid Services elected not to make a specific recommendation regarding how this should be done. The Alzheimer’s Association recommends reviewing the patient’s health risk assessment (HRA), asking the patient and any family/friends present about cognitive decline concerns, and observing the patient during the visit. These questions will help identify any deficits in ADLs or instrumental ADLs (IADLs) such as cooking, shopping, etc. If any concerns exist based on this information, screening with a brief structured patient-completed assessment such as the General Practitioner Assessment of Cognition (GPCOG), the Memory Impairment Screen (MIS), the Mini-Cog, or the Mini-Mental State Exam (MMSE) is recommended. If screening with informant input, the Alzheimer’s Association suggests using the GPCOG (patient and informant information can be combined for improved sensitivity and specificity), AD8, or the short Informant Questionnaire on Cognitive Decline in the Elderly (Short IQCODE). Of note, the Alzheimer’s Association algorithm also suggests screening any patient who does not have an informant present with a structured tool (Cordell et al., 2013).  

In 2014, Barnes et al. developed and published a dementia screening indicator for PCPs. It includes a point system and is designed to help a PCP decide quickly if a patient is appropriate for formal screening with an assessment tool such as the GPCOG, Mini-Cog or MIS. First and foremost, if the patient or family expresses cognitive concerns, it recommends formal screening. Over age 80, it also recommends formal screening. However, if there are no explicit cognitive concerns, and the patient is age 65-79, the points are assigned based on:

• Age 
• Years of education 
• BMI 
• History of type 2 diabetes 
• Stroke 
• Assistance required to manage medications/finances 
• Depression 

If the total score is greater than or equal to 22, they recommend formal screening using a validated screening tool (Barnes et al., 2014).

In 2015, the Gerontological Society of America (GSA) published their own recommendations for cognitive impairment detection, intentionally omitting the words mild and screening. Their intention was to incorporate this into the Medicare AWV. Their final recommendation was in the form of a four-step flowsheet:

• STEP 1: Kickstart the cognition conversation 
• STEP 2: Assess if symptomatic 
• STEP 3: Evaluate with full diagnostic workup if cognitive impairment detected.
• STEP 4: Refer to community resources and clinical trials, depending on the diagnosis.

Their recommendations were that PCPs routinely ask patients about any cognitive changes, and formally screen/assess any patients who express concern, whose family/friends express concern, or who exhibit signs/symptoms of cognitive impairment during the visit. If the screen is positive, the patient should be fully evaluated or referred to an outside provider for evaluation (GSA, 2015). 

Formal Screening

Positives features of the GPCOG, MIS, Mini-Cog, and MMSE include brevity (less than five minutes to administer), validation in a primary care setting, easy administration by a non-physician, good to excellent psychometric properties, and a relative lack of educational, language, or cultural bias. An important downside of the MMSE is an associated copyright fee from the authors; the other three options are currently free of charge. The MMSE has been shown to have some education, age, language, and cultural bias as well as a ceiling effect in which highly-educated individuals may pass despite significant impairment. Despite all of this, it is the most widely studied and therefore verified of the options available. If the brief assessment triggers concerns based on the score then referral for full assessment should be made, or a full assessment conducted (may be done same day with correct billing codes if an informant is present) (Cordell et al., 2013).  The full evaluation should also consist of an assessment of functional status. A caregiver or family member/spouse can provide structured objective information using the Functional Activities Questionnaire or similar.

The tests discussed above can also be used to monitor disease progression. For example, the CCCDTD4 suggests that a three-point decline in a patient’s MMSE score within a six-month time frame carries a poor prognosis and should therefore prompt the provider to explore comorbid conditions and review pharmacological management (Moore et al., 2014). In 2014, the US Preventive Services Task Force (USPSTF) concluded that the current evidence was insufficient to assess the risks/benefits of formal universal screening of all adults over the age of 65 (I statement) (Moyer, 2014).

Staging

The staging of dementia can be done with multiple tools, but three that are commonly cited and utilized include the functional assessment staging tool (FAST, see Table 2 below), the global deterioration scale (GDS, see Table 3 below), and the clinical dementia rating scale (CDR). While the FAST looks at the patient’s functional abilities and ADLs, the GDS focuses more on cognition. Both can be helpful in monitoring patients progress through the disease, as well as decision making and educating patients and caregivers. 

The CDR is focused more on testing memory and performs better when assessing for amnestic (highlighted by memory loss) MCI. It is also less effective at detecting very mild dementia (Dementia Care Central, 2018; Panegyres et al., 2016).

Advanced AD or dementia can be especially challenging to manage. Referrals to care facilities are usually required when the burden of care extends beyond the capabilities of the family. Care decisions should be guided by carefully considered overall goals of care, whether that be a desire for all interventions that may prolong life, comfort care only, or something in between. This is best done directly by the patient though advance directives whenever possible, as this relieves the pressure and stress off of the proxy decision maker. In the absence of an advance directive, the proxy will have to do their best to make substitute judgements or a decision based on the best interest of the patient (Mitchell, 2015). 

Treatment

Realistic and achievable treatment goals for AD do not currently include curing the disease, but slowing deterioration, improving/preserving independence with ADLs and cognitive function, reducing caregiver burden, improving quality of life, creating a safe environment, increasing social engagement, enhancing mood and behavior, and finally managing any behavioral and psychological symptoms (BPSD) (Pandya, 2018). The decision of whether to treat a patient or refer is a complicated one for many PCPs. The CCCDTD4 recommends that PCPs refer dementia and AD patients to a specialist, such as a memory clinic with access to genetic testing and counseling, in certain circumstances. For example, in EOAD there are special circumstances that would warrant the resources of such a referral. Patients diagnosed with rapidly progressive dementia (RPD) which develops within 12 months of the first symptoms should also be referred to a practice with expertise in this subtype of patients once other causes for the symptoms have been adequately ruled out (Moore et al., 2014).

Nonpharmacological treatments for AD and dementia include getting regular medical care to manage comorbidities as well as regular exercise and obtaining regular cognitive stimulation. Supplements such as vitamin C, D, E, ginkgo biloba, and omega-3 fatty acid supplements have been shown to have little to ne effect in preventing cognitive decline. A key in the effective management of AD is educating the patient and caregiver(s) regarding the diagnosis and prognosis and encouraging connection with others living with dementia and a focus on activities that bring purpose to life (Alzheimer’s Association, 2019). Other helpful items include resources for patients regarding social support through local, regional, and national organizations such as the Alzheimer’s Association, Alzheimer’s Foundation of America, and other local groups. Items that will help with daily functioning include calendars, to-do lists, technology/assistance for medication management (pill box, reminder, dispenser, or organizer) and safety (emergency response system, door alarms, etc.). When appropriate and available, patients should be referred to open/enrolling clinical trials (NIA, 2016). Patients and their families should be encouraged to complete all necessary legal, financial, and long-term care planning early in the disease process while reasoning and communication skills are still intact; this includes a will, living will/advance directives, as well as a power of attorney, both healthcare and financial. Home safety and driver safety should be routine conversations that occur at each healthcare visit with someone diagnosed with AD or other dementia to ensure safety measures are in place. Research and distribute local resources for driving evaluations, and if needed, a home safety evaluation may be paid for by the patient’s Medicare coverage through a local home health agency. Patients should be encouraged to stick to familiar places and try to establish a regular daily routine. When needed, patient should be referred to physical therapy for assistance ambulating safely to limit the risk of falls and occupational therapy for assistance with independent living skills. For patients that are still working and having difficulty with job performance, suggest reducing hours or switching to a less demanding position and encourage the patient to consult with their employer’s human resources department regarding employee assistance programs, family leave, and long-term disability benefits (NIA, 2017a).

Pharmacological treatments currently include five FDA-approved medications. Three of these are cholinesterase inhibitors (ChEIs) that function by reversibly binding to and thus inactivating acetylcholinesterase. This includes donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon). Donepezil (Aricept) is approved for all stages of AD, available in a tablet as well as an orally disintegrating tablet (ODT), and dosed once daily. Galantamine (Razadyne) is available in both immediate release tablet (dosed twice daily, or BID) and extended release tablet (dosed daily) as well as a liquid solution. Rivastigmine (Exelon) is available as a capsule that is dosed BID, or a transdermal patch (Pandya, 2018). Galantamine and rivastigmine are approved for mild to moderate AD. Common adverse effects of ChEIs include nausea, vomiting, poor appetite, and increased frequency of bowel movements (Alzheimer’s Association, n.d.a). The fourth medication available, memantine (Namenda), functions as a N-methyl-D-aspartate (NMDA) receptor antagonist and regulates the activity of glutamate. This is believed to slow the influx of Ca+ into neurons and thus slow the process of nerve damage. It is available as an oral solution, a twice daily immediate release tablet, or a once-daily extended release capsule. Common adverse effects include headache, constipation, confusion, and dizziness. There is also a combination product of memantine and donepezil (Namzaric) which is dosed once daily in a capsule containing both immediate and extended-release components. Both memantine (Namenda) and memantine/donepezil (Namzaric) are only approved for moderate to severe AD. All of these medications modestly improve cognitive function and may delay nursing home placement but should be stopped in the late stages of the disease (Alzheimer’s Association, n.d.a; Pandya, 2018). 

The CCCDTD4 states that any differences between the options of ChEIs are largely based on adverse effect profiles and pharmacokinetics, not efficacy. They list potential adverse effects of peripheral cholinergic stimulation related to ChEIs as:

• Increased risk of GI bleeding (caution in patients with a history of ulcers or taking anti-inflammatory drugs);
• Increased risk of bradycardia/heart block (in patients with or without cardiac impairment);
• Exacerbation of asthma or other pulmonary diseases;
• Urinary obstruction;
• Increased risk of seizures;
• Prolonged effects of succinylcholine, a muscle relaxant (Moore et al., 2014).

The Canadian group also agreed that medications could and should be stopped when desired by the patient or caregiver, when the patient is noncompliant, when the patient is experiencing intolerable side effects, when comorbidities make continued treatment too risky or futile, if ineffective (when the patient’s rate of decline is greater on the medication than prior to starting), or when the patient’s dementia progresses to a stage (GDS 7) where there would be no meaningful benefit from continued treatment. ChEIs should be tapered and not stopped abruptly. They also recommend that if medication is stopped due to perceived ineffectiveness, the patient should be monitored closely for one to three months after stopping for an observable decline and consider restarting medication in those cases (Moore et al., 2014).

Behavioral and Psychological Symptoms of Dementia (BPSD)

BPSD affect up to 90% of patients with moderate to severe dementia. BPSD include depression, hallucinations, agitation, aggression, wandering, and “sun-downing” (worsening cognition and behavioral symptoms later in the afternoon/evening). BPSD contribute to caregiver stress and burnout, and can lead to weight loss, falls, infection, incontinence, and institutionalization. Dementia patients with new-onset BPSD should undergo a medical evaluation to rule out pain, constipation, infection, vision/hearing loss, depression, sleep disorders, and/or adverse effects from medications. If a specific trigger in their environment (such as overstimulation, a medication, or a particular caregiver) can be identified, they should be removed if possible. Non-pharmacological treatments for BPSD include behavioral changes such as:

• Establish and maintain a consistent daily routine;
• Routine physical activity and optimized nutrition (but include comfort foods);
• Incorporate enjoyable activities such as art, music, and spirituality;
• Allow for regular reminiscing and story-telling;
• Aromatherapy;
• Caregivers should not disagree or argue with the patient;
• Caregivers should show respect when interacting;
• Maintain good eye contact but allow physical space when interacting;
• Avoid scolding or threatening; instead use a calm, slow voice when speaking;
• Validate and reassure (Pandya, 2018).

If these modifications do not alleviate the BPSD, then a medical professional should consider and evaluate the risks versus benefits of medications. There are currently no FDA-approved medications for the treatment of BPSD, but commonly used medications include antipsychotics, benzodiazepines, antidepressants, and anticonvulsants. There is a black box warning from the FDA that all antipsychotics increase the risk of mortality in patients with behavioral disorders. They can also cause neuroleptic malignant syndrome, extrapyramidal symptoms, cerebral adverse events, increased risk of falls, sedation, QTc prolongation, metabolic syndrome/weight gain, and sudden death. Olanzapine (Zyprexa) can cause syncope (Pandya, 2018). Despite these risks, the CCCDTD4 listed risperidone (Risperdal), olanzapine (Zyprexa), or aripiprazole (Abilify) as potential treatment considerations in AD patients with severe agitation/aggression and psychosis if there is risk of harm to self or others, but valproate (Depakene, Depacon) should not be considered for this indication due to risk of toxicity, accelerated brain volume loss, and greater cognitive impairment (Moore et al., 2014). The 2015 Beers Criteria, published by the American Geriatric Society, submits strong evidence to avoid the use of antipsychotics in dementia patients with behavioral issues unless the patient is a threat to themselves or others and only after nonpharmacological treatments have been tried and failed due to the increased risk for stroke and mortality (Terrery & Nicoteri, 2016). Benzodiazepines carry their own significant list of risks, as they can cause depression, confusion, sedation, increased risk of falls/fractures, stroke/cerebral adverse events, sleep disturbance, and delirium (Pandya, 2018). The 2015 Beers Criteria states there is strong evidence to avoid the use of benzodiazepines in the treatment of agitation in the elderly secondary to the increased risk of falls (Terrery & Nicoteri, 2016). The CCCDTD4 states that there is insufficient evidence to support the use of selective serotonin reuptake inhibitors (SSRIs) or trazodone (Oleptro) for the treatment of agitation in patients with AD. However, they point out that a trial of antidepressant medication could be considered in the case of a major depressive disorder, severe dysthymia, or severe emotional lability (Moore et al., 2014).

Common Complications

Common complications encountered in advanced dementia include eating problems and infections. Eating problems such as oral dysphagia, pharyngeal dysphagia, inability to feed oneself, or refusal to eat are the most common complications in advanced AD. As always, the patient should be evaluated and treated for any acute or reversible conditions (i.e., a tooth abscess). Conservative measures such as smaller meals, altered food textures, and high-calorie supplements may help with intake. However, the literature demonstrates that of these options, only supplementation has been shown to promote weight gain, and none of the above interventions affected function or survival. More aggressive options include hand feeding and tube feeding. Hand feeding is time consuming and labor intensive but allows patients to enjoy tasting food and encourages social interaction with caregivers. A 2009 Cochrane review found insufficient evidence to support tube feeding in patients with advanced dementia, as it did not significantly improve survival, quality of life, nutrition, functional status, prevention of aspiration, or the prevention or healing of pressure ulcers. There are risks associated with tube feeding, such as insertion complications, tube blockages, tube dislodgments, and the use of restraints if patients attempt to remove or otherwise interfere with the tube itself (Mitchell, 2015). 

Infections are another extremely common complication in patients with advanced dementia, especially of the urinary tract and respiratory tract. In one study, between 52-66% of advanced dementia patients in a nursing home were prescribed antibiotics in the last 12 months. Inability to communicate the presence of any subjective symptoms such as dysuria or chest pain compounds the difficulty in diagnosing and treating infections in this group of patients.  As previously stated, clearly established goals of care will help guide treatment decisions in this instance as well. If antimicrobials are determined to be the best course of action, the least invasive route of administration should be used, and hospitalization should be avoided if possible (Mitchell, 2015).

Regarding end of life care, referrals to palliative and/or hospice care should be made when deemed appropriate in patients with advanced AD. A major limitation for enrollment in hospice care is a requirement for a life expectancy of six months or less. Currently, in order to qualify for hospice care for advanced dementia, Medicare requires a rating of 7c-f on the FAST scale with all the features of stages 6a-7c (see Table 2 above for details of the FAST scale stages 6a-7c). The patient must have also had a medical complication in the previous year such as aspiration pneumonia, pyelonephritis or other upper urinary tract infection (UTI), septicemia, multiple pressure ulcers (stage 3-4), recurrent fevers after treatment with antibiotics, or eating problems (defined as food/fluid intake that is insufficient to sustain life, a weight loss of greater 10% during the previous six months or serum albumin less than 2.5g/dL). Observational studies of advanced dementia patients enrolled in hospice care have shown less hospitalizations, higher frequency of treatment for pain and dyspnea, and families that have greater satisfaction with patient care. If referral to a palliative care or hospice care specialist is available, these options should be offered and discussed with the patient’s health care proxy (Mitchell, 2015).

Research

Given the pathophysiological findings of the plaques and tangles seen in AD, researchers are attempting to develop a noninvasive method for identifying the disease earlier. The most active area of research currently is that of molecular imaging of beta-amyloid deposits. PET scanning with fluorodeoxyglucose (FDG-PET) is being developed and improved to potentially identify areas of decreased glucose intake in certain regions of the brain that may identify abnormal or pathological activity, but so far patterns of reduced activity have not been shown to provide diagnostic information in any one individual patient. Cerebrospinal fluid (CSF) testing for biomarkers may eventually be used to complement the clinical diagnosis of AD, but at this time it is primarily being used in research trials. Biomarker ratios have a higher accuracy than single biomarkers and are most useful in discriminating AD samples from normal controls, but there is significant measurement variability. Changes in 42-residue isoform of beta-amyloid (Ab42), Tau, and phosphorylated Tau (pTau) may eventually allow the diagnosis of AD in its prodromal stage. If all three levels are normal, AD can be ruled out confidently. The Alzheimer’s Association is funding a quality control program for these biomarkers (Pandya, 2018). 

In addition to diagnostics, trials are ongoing regarding new and emerging treatments. Pioglitazone (Actos) is a thiazolidinedione that increases insulin sensitivity and is being studied in 3,500 asymptomatic people with known genetic mutations for AD to reduce insulin resistance. Crenezumab is an immune-based therapy that produces antibodies against beta-amyloid that is currently being tested in patients with positive genetic mutations by the Alzheimer’s Prevention Initiative’s (API) Autosomal Dominant Alzheimer’s Disease (ADAD) trial. A monoclonal antibody that targets beta-amyloid called solanezumab is being tested in asymptomatic patients with high levels of amyloid on PET scans in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study (A4) (Alzheimer’s Association, n.d.b; Pandya, 2018). Solanezumab is also being tested in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) in combination with another drug, gantenerumab, in patients with mutations on chromosomes 1, 14, or 21. The DIAN-TU team is hoping to show evidence that these two medications remove excess beta-amyloid from the brain. The two enzymes, beta-secretase and gamma-secretase, that are responsible for clipping pieces of amyloid precursor protein (APP) to form beta-amyloid are current subjects of research for potential drug treatments of the future. In fact, researchers are investigating potential ways to interfere with the process at almost every point in the amyloid processing pathway. Posiphen is a medication designed to inhibit APP production and is currently in Phase I clinical trials to establish safety, tolerability, dosing, and pharmacokinetics/pharmacodynamics with an estimated completion date of December 2020. JNJ-54861911 works by inhibiting the activity of beta-secretase and is in Phase 3 trials scheduled to end in 2024 to determine if it slows cognitive decline in healthy people with elevated levels of beta-amyloid in the brain. The Generation Study, under the umbrella of the API, is testing the effects of two investigational drugs. They are attempting to determine if an active immunotherapy called CAD106 and a beta-secretase inhibitor CNP520 can prevent/delay the onset of AD symptoms in healthy older adults with two copies of the high-risk APOE allele Ɛ4. Tau protein, the chief component of tangles, is being targeted as a treatment option as well. AADvac1 is a vaccine in Phase II clinical trials that were completed in June of 2019 to stimulate the immune system to attack the abnormal form of tau protein seen in Alzheimer’s disease. The results were positive, and the vaccine’s developer is looking for a global partner with which to continue the next level of study. The inflammation seen in the brains of patients with AD is being studied as well. Sargramostim (GM-CSF, Leukine) is already approved for use in leukemia patients; it functions by stimulating the bone marrow to elicit an immune response that may protect neurons from toxic proteins by attacking abnormal beta-amyloid plaques. The Phase II study for sargramostim that is estimated to be completed in May 2020 has shown significant improvement in cognitive function compared to placebo. Pimavanserin is an inverse agonist for the 5-HT2A receptors in the brain, having the opposite effect of serotonin, and potentially decreasing communication between neurons and reducing the symptoms of dementia-related psychosis. The Phase III clinical trial is expected to be completed in September of 2020. The Alzheimer’s Association provides a service that matches patients with over 250 existing available clinical trials called TrialMatch (Alzheimer’s Association, n.d.b). In 2017, the WHO launched a global action plan to help improve the lives of people with dementia worldwide, reduce caregiver burden, and decrease the impact of dementia on communities and countries. It aims to accomplish this by increasing prioritization and awareness of dementia, reducing the risk of dementia, improving diagnosis/treatment/care of dementia patients, supporting dementia caregivers, strengthening information systems for dementia, as well as research and innovation. In December of 2017, the WHO Global Dementia Observatory was launched to help collect and organize worldwide data to help researchers across the globe share information and function as a team to work towards a potential solution to AD (WHO, 2019).

References

Alzheimer's Association. (n.d.a). Health systems and clinicians. Retrieved January 23, 2020, from https://www.alz.org/professionals/health-systems-clinicians

Alzheimer's Association. (n.d.b). Treatment horizon. Retrieved January 23, 2020, from https://www.alz.org/alzheimers-dementia/research_progress/treatment-horizon

Alzheimer’s Association. (2019). Alzheimer’s disease facts and figures. https://alz.org/media/Documents/alzheimers-facts-and-figures-2019-r.pdf

Barnes, D. E., Beiser, A. S., Lee, A., Langa, K. M., Koyama, A., Preis, S. R., Neuhaus, J., McCammon, R. J., Yaffe, K., Seshadri, S., Haan, M. N., & Weir, D. R. (2014). Development and validation of a brief dementia screening indicator for primary care. Alzheimers & Dementia, 10(6), 656-665. https://doi.org/10.1016/j.jalz.2013.11.006

Brodaty, H., Connors, M. H., Loy, C., Teixeira-Pinto, A., Stocks, N., Gunn, J., Mate, K. E., & Pond, C. D. (2016). Screening for dementia in primary care: A comparison of the GPCOG and the MMSE. Dementia and Geriatric Cognitive Disorders, 42(5-6), 323-330. https://doi.org/10.1159/000450992

Cordell, C. B., Borson, S., Boustani, M., Chodosh, J., Reuben, D., Verghese, J., Thies, W., Fried, L. B., & Medicare Detection of Cognitive Impairment Workgroup (2013). Alzheimer’s Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimers & Dementia, 9(2), 141-150. https://doi.org/10.1016/j.jalz.2012.09.011

Dementia Care Central. (2018). Stages of Alzheimer’s & dementia: Durations & scales used to measure progression: GDS, FAST & CDR. https://www.dementiacarecentral.com/aboutdementia/facts/stages/

Edwards, G. A., Gamez, N., Escobedo Jr., G., Calderon, O. & Moreno-Gonzalez, I. (2019). Modifiable risk factors for Alzheimer’s disease. Frontiers in Aging Neuroscience, 11, 146. https://doi.org/10.3389/fnagi.2019.00146

Gerontological Society of America. (2015). The Gerontological Society of America workgroup on cognitive impairment detection and earlier diagnosis report and recommendations. https://www.geron.org/images/gsa/documents/gsaciworkgroup2015report.pdf

Marseglia, A., Wang, H. X, Rizzuto, D., Fratiglioni, L., & Xu, W. (2019). Participating in mental, social, and physical leisure activities and having a rich social network reduce the incidence of diabetes-related dementia in a cohort of Swedish older adults. Diabetes Care, 42(2), 232-239. https://doi.org/10.2337/dc18-1428

Mitchell, S. L. (2015). Advanced dementia. New England Journal of Medicine, 372(26), 2533-2540. https://doi.org/10.1056/nejmcp1412652

Moore, A., Patterson, C., Lee, L., Vedel, I., & Bergman, H. (2014). Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia: Recommendations for family physicians. Canadian Family Physician, 60(5), 433-438. Retrieved from http://www.cfp.ca/content/60/5/433/tab-article-info

Moyer, V. A. (2014). Screening for cognitive impairment in older adults: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine, 160(11), 791. https://doi.org/10.7326/m14-0496

National Institute of Neurological Disorders and Stroke. (2019). Alzheimer's disease information page. https://www.ninds.nih.gov/Disorders/All-Disorders/Alzheimers-Disease-Information-Page

National Institute on Aging. (n.d.). Alzheimer's disease diagnostic guidelines. Retrieved October 26, 2018, from https://www.nia.nih.gov/health/alzheimers-disease-diagnostic-guidelines

National Institute on Aging. (2016). Managing older patients with cognitive impairment. https://www.nia.nih.gov/health/managing-older-patients-cognitive-impairment

National Institute on Aging. (2017a). Now what? Next steps after an Alzheimer's diagnosis. https://www.nia.nih.gov/health/now-what-next-steps-after-alzheimers-diagnosis

National Institute on Aging. (2017b). What happens to the brain in Alzheimer's disease? https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease

National Institute on Aging. (2019). Alzheimer's disease genetic fact sheet. https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet

Pandya, N. (2018). Advanced insights into the prevention, treatment and management of Alzheimer's disease. Journal of Managed Care Medicine, 21(2), 52-57.

Panegyres, P. K., Berry, R., & Burchell, J. (2016). Early dementia screening. Diagnostics, 6(1), 6-20. https://doi.org/10.3390/diagnostics6010006

Terrery, C. L., & Nicoteri, J. A. (2016). The 2015 American Geriatric Society Beers Criteria: Implications for nurse practitioners. The Journal for Nurse Practitioners, 12(3), 192-200. https://doi.org/10.1016/j.nurpra.2015.11.027

World Health Organization. (2019). Dementia: A public health priority. http://www.who.int/mental_health/neurology/dementia/en/