Alzheimer's Disease Nursing CE Course for APRNs

glia and astrocytes. These cells are normally responsible for engulfing and destroying waste/toxins in a healthy brain but do not function properly in destroying beta-amyloid plaques in AD. In addition to failing to clear the plaques and other cellular debris, they collect around neurons and emit pro-inflammatory biochemicals. Research suggests that a reduced permeability of the blood–brain barrier in patients with AD contributes to the development of the condition by preventing sufficient glucose delivery to neurons and impairing waste removal. Vascular issues such as atherosclerosis, transient ischemic attacks, and strokes are also common in patients with AD, further compounding the existing pathology (Huang, 2025; Lui & Tsao, 2024; NIA, 2024b).

Early-onset familial AD (EOAD or FAD) develops in individuals before the age of 65, usually between 30 and 60, accounting for less than 10% of all AD. Some EOAD is believed to be caused by an autosomal mutation in one of three separate genes on chromosomes 1, 14, or 21. Each of these mutations affects the breakdown of APP (part of the process that leads to amyloid plaque formation) by altering the formation of presenilin 1 (PSEN1; chromosome 14), presenilin 2 (PSEN2; chromosome 1), or APP (chromosome 21). In late-onset AD (the most common form, developing in the mid- to late 60s), researchers have found a genetic risk factor via the apolipoprotein E (APOE) gene on chromosome 19. Of the three known alleles of APOE, one is thought to be protective against AD (APOE Ɛ2), one neutral (APOE Ɛ3), and one increases the risk of AD as well as being associated with an earlier age of onset (APOE Ɛ4). Each individual has two copies of the APOE gene and thus has a combination of zero, one, or two of each of the foregoing alleles as a possibility. Currently, APOE allele testing is available and used in research studies to evaluate disease risk in large groups of people, but it is not yet used or helpful in determining an individual’s risk. Genetic tests are not routinely done in the clinical setting to diagnose or predict AD; however, in some cases, if an individual has symptoms at an early age with a strong family history, a neurologist may order a genetic test (e.g., APP, PSEN1, and PSEN2). With the availability of at-home genetic tests, some people may learn their APOE status using these kits. Research into a genetic link to AD has come a long way, with only 10 genes identified to be associated with AD 10 years ago; currently, scientists have identified 70 genetic regions associated with AD (Lui & Tsao, 2024; NIA, 2023a, 2024a; Sherva, 2025).

More recent research has focused on the duration of the presymptomatic period associated with AD, specifically the period between the onset of pathophysiologic processes in the brain and the presentation of clinical symptoms. Researchers have found a long presymptomatic period in many cases, suggesting that additional research is necessary during the younger years to determine the impact of lifestyle and environmental determinants. For example, some researchers have found that although the average age of diagnosis for dementia is 82, many of these individuals noticed memory loss up to 16 years before the diagnosis. A long presymptomatic period has been found in individuals with inherited AD due to a mutation in APP, PSEN1, or PSEN2. For these individuals, a decline in amyloid beta 1 through 42 was found in cerebrospinal fluid (CSF) 25 years before disease onset, and amyloid in the brain, phospho-tau in CSF, and brain atrophy on magnetic resonance imaging (MRI) were present 15 years before the disease onset (Keene & Montine, 2025).

Prevention

The treatment of AD is suboptimal currently, as they generally cannot cure or reverse the disease, serving only to manage symptoms or slow down the progression of the disease in the best of scenarios. Therefore, much emphasis has been placed on preventing AD instead of waiting for treatment options to improve. Prevention of AD has been studied, and thus far, managing cardiovascular risk and stroke prevention appear to be the most effective. This management includes mitigation of any modifiable risk factors as well as aggressive management of cardiovascular disease, diabetes, hypertension, stroke/ischemia, elevated BMI, epilepsy, depression, and hypercholesterolemia. Diabetes has been estimated to increase an individual’s risk of AD by 50%–100% and vascular dementia by 100%–150%. The mechanism behind this likely involves both micro- and macrovascular disease, direct damage to the central nervous system secondary to hyperglycemia, and increased inflammation secondary to insulin resistance (Alzheimer’s Association, 2025; Huang, 2025; Keene & Montine, 2025; Press & Arvanitakis, 2026).

Conversely, weight loss, physical activity, a diet lower in saturated fats and rich in omega-3 fatty acids (such as the Mediterranean diet) are thought to protect against AD. Observational studies have found an association between a Mediterranean diet and a decreased risk for dementia. Similarly, observational studies have found an association between the MIND diet (i.e., a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension [DASH] diet) and a decreased risk of dementia. Sleep disturbances increase the risk of AD, as sleep helps clear the brain of waste products, including amyloid and Tau, and sleep disturbances are among the earliest symptoms observed in patients with AD. Research regarding the impact of smoking and nicotine on AD risk is still unclear. Cognitive decline in individuals who smoke is directly related to the number of packs per day and has a negative effect on cardiovascular disease, a known risk factor for AD. However, nicotine appears to reduce APP secretion and inhibit amyloid aggregation, and epidemiologic studies indicate that smoking may not be associated 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. However, 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 prevent AD. Research has also demonstrated that dietary supplements or herbal remedies (e.g., vitamin E and other antioxidant vitamins, vitamin B6, B12, folate, and ginkgo biloba), cholinesterase inhibitors, and nonsteroidal anti-inflammatory (NSAIDs) and aspirin (ASA) have not been shown to prevent AD and may harm patients (Alzheimer’s Association, 2025; Huang, 2025; Keene & Montine, 2025; Press & Arvanitakis, 2026; Safiri et al., 2024). Prospective studies dating back to 2003 indicate that regular physical, mental, or socially stimulating leisure activities reduce 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

Initial Screening

AD should be suspected in any older adult presenting with subtle and progressive memory decline and dysfunction in at least one other cognitive domain, leading to impaired functioning. Healthcare providers (HCPs) should conduct a detailed cognitive and neurologic examination. In 2013, the Alzheimer’s Association published recommendations for HCPs to better detect cognitive decline as a standard component of the Medicare annual wellness visit (AWV), an added benefit of the 2010 Affordable Care Act. The AWV includes the detection of any cognitive impairment as one of its seven components. However, 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. Potential options for questions to include in the HRA that have been tested through the Behavioral Risk Factor Surveillance System include (Alzheimer’s Association, n.d.-a; Cordell et al., 2013):

• During the past 12 months, have you experienced confusion or memory loss that is happening more often or getting worse?
• During the past 7 days, did you need help to perform everyday activities such as eating, getting dressed, grooming, bathing, walking, or using the toilet?
• During the past 7 days, did you need help to take care of things such as laundry, housekeeping, banking, shopping, using the telephone, food preparation, transportation, or taking your medications?
• 
  

These questions will help identify deficits in ADLs or instrumental ADLs (IADLs) such as cooking and shopping. 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, the Mini-Mental State Exam (MMSE), or the Montreal Cognitive Assessment (MoCA) is recommended. The MoCA is often the preferred assessment tool because it has better sensitivity for executive and language dysfunction than other tools, such as the MMSE. The typical cutoff for normal performance on the MoCA is 26, with scores of 25 and below considered abnormal. The MoCA is available online and in several languages. 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), Aging and Dementia (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 (Alzheimer’s Association, n.d.-a; Cordell et al., 2013; Wolk & Dickerson, 2024).

              In 2014, Barnes and colleagues developed and published a dementia screening indicator for HCPs. This screening indicator was based on the collective data of four large cohort studies (the Cardiovascular Health Study, the Framingham Heart Study, the Health and Retirement Study, and the Sacramento Area Latino Study on Aging). It includes a point system designed to help an HCP decide quickly if a patient is appropriate for formal screening with one of the assessment tools mentioned previously. First and foremost, if the patient or family expresses cognitive concerns, formal screening is needed. Formal screening is also recommended for individuals over the age of 80 (Barnes et al., 2014). However, if there are no explicit cognitive concerns, and the patient is aged 65–79, the points are assigned based on the following:

• age (+1 point per year over 65)
• years of education (+9 points if less than 12 years of education)
• BMI (+8 points if BMI < 18.5kg/m²)
• history of type 2 diabetes (+3 points if positive history)
• stroke (+6 points if positive history)
• assistance required to manage medications/finances (+10 points if yes)
• depression (+6 points if yes, based on the current use of antidepressant medication, or reports that “everything was/is an effort” at least 3 days per week over the past week; Barnes et al., 2014)

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 its recommendations for cognitive impairment detection, intentionally omitting the words mild and screening. They intended to incorporate this into the Medicare AWV. Their final recommendation was in the form of a four-step flowsheet (GSA, n.d.; Tracy, 2023):

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

The GSA recommends that HCPs routinely ask patients about any cognitive changes and formally screen/assess 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 HCP for evaluation (GSA, n.d.; Tracy, 2023).

Formal Screening

Positive features of the MIS, Mini-Cog, MoCA, and MMSE include brevity (less than 5 minutes to administer); validation in a primary care setting; easy administration by a non-HCP; good to excellent psychometric properties; and a relative lack of education, language, or cultural bias. The GPCOG has been shown to have a low educational bias, but there is not sufficient data regarding any potential language or cultural bias. A limitation cited for the GPCOG is the indeterminate range in the middle if it is used without an informant score and a low specificity if the informant score is being used alone. The MIS is a verbal-only test that requires no writing/drawing; it does not test executive function or visuospatial skills. Limitations of the Mini-Cog include variability in failure rates based on using different word lists and that some of the study results are based on longer tests with the Mini-Cog elements reviewed independently. An important downside of the MMSE is the 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 verified of the available options. Based on the Alzheimer’s Association AWV algorithm, if the brief assessment triggers concerns based on the score (GPCOG less than 5 [a score of 5-8 is considered indeterminant and requires an informant score], MIS less than or equal to 4, Mini-Cog less than or equal to 3, AD8 great than or equal to 2, Short IQCODE greater than or equal to 3.38, or MoCA less than or equal to 25), then referral for a full assessment should be made, or a full assessment conducted (may be done the 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/significant other can provide structured, objective information using the Functional Activities Questionnaire or a similar tool with a cutoff score of 6 points or greater; this results in 85% accuracy for differentiating mild cognitive impairment (MCI) from dementia (Alzheimer’s Association, n.d.-a; Cordell et al., 2013; Wolk & Dickerson, 2024). A list of related dementias and defining characteristics can be found in Table 1 to help the HCP differentiate AD from other similar forms of dementia.

Table 1

Clinical Differentiation of Common Dementias

Disease	Initial Symptoms	Cognitive Impairment	Mental State Examination	Neurologic Examination	Imaging Findings
AD	Episodic memory loss	Memory loss initially, followed by all cognitive domains	Normal in the early stage	Normal in the early stage	Atrophy in the entorhinal, cortex, and hippocampus
Vascular dementia	Sudden onset with steady deterioration, falls, apathy, and focal weakness	Executive and frontal function and generalized slowing, memory may be intact	Apathy, anxiety, and delusions	Focal neurologic deficits, weakness, and spasticity	White matter disease with cortical/ subcortical infarctions
Lewy body dementia	Visual hallucinations, rapid eye movement (REM) sleep disorder, delirium, and Parkinsonism	Drawing, frontal, and executive; memory intact	Delirium/ delusions, hallucinations, and depression	Parkinsonism	Larger hippocampus than AD with posterior parietal atrophy
Fronto-temporal dementia	Apathy, behavioral/ personality changes, compromised judgment, speech/ language difficulties	Effects frontal, executive, and language; memory and drawing spared	Apathy, hyperorality, and disinhibition	Vertical gaze palsy, axial rigidity, and dystonia may be normal if they overlap with progressive supranuclear palsy/ corticobasal degeneration	The posterior parietal is spared, but frontal or temporal atrophy is expected

(Huang, 2025; NIA, 2025a)

The tests discussed previously can also be used to monitor disease progression. For example, the fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5) suggests that a 3-point decline in a patient’s MMSE score within 6 months carries a poor prognosis and should prompt the HCP to explore comorbid conditions and review pharmacologic management (Hermann & Zerr, 2022; Ismail et al., 2020). In 2020, the US Preventive Services Task Force (USPSTF) reaffirmed their 2014 recommendation that the current evidence was insufficient to assess the risks/benefits of formal universal screening of all adults over 65 (USPSTF, 2020). The CCCDTD5 also recommended against cognitive testing to screen asymptomatic adults for MCI or dementia, including those at risk (Ismail et al., 2020; Larson, 2025).

Diagnosis

A detailed clinical assessment of cognitive and functional decline provides reasonable diagnostic accuracy for AD in most patients. A conclusive AD diagnosis occurs only after a positive autopsy (i.e., histologic evaluation of brain tissue). However, recent advances in neuroimaging and the detection of molecular biomarkers (such as beta-amyloid and Tau) are now carrying a level of certainty approaching that of an autopsy diagnosis (Ismail et al., 2020; McKhann et al., 2011; Wolk & Dickerson, 2024). In 2011, a joint workgroup from the NIA and the Alzheimer’s Association put forth the clinical diagnostic criteria for AD, which describes three stages of the disease: preclinical (cognitively unimpaired), MCI, and AD. Although significant progress has been made in biomarker research, the 2011 criteria are still the most widely used criteria for clinical practice (McKhann et al., 2011). In 2018, the NIA and Alzheimer’s Association workgroup published a research framework by which they defined AD biologically based on its underlying pathologic processes documented by biomarkers instead of symptoms. The biomarkers are grouped into those with beta-amyloid deposition, pathologic tau, and neurodegeneration (ATN classification). The ATN classification is flexible, allowing new biomarkers to be added to these three categories when they become available. The workgroup highlighted that this framework is for research purposes and is not meant for use in clinical practice. They recommend that the three-stage syndromal categories still be used in clinical practice (Jack et al., 2018). In 2024, the Alzheimer’s Association workgroup published updated objective (biologic) criteria for the diagnosis of AD based on advances in biomarkers. These updated criteria are meant to serve as general principles to inform diagnosis and staging, as reflected by current science but are not intended to serve as a clinical practice guideline or treatment protocol. Given that biomarker testing is not widely available, more work needs to be done to bridge these new recommendations from research to clinical practice (Jack et al., 2024).

The clinical diagnostic criteria, including the three stages (preclinical, MCI, and AD), are still widely accepted and used in practice. In the preclinical stage, there are no evident symptoms, only underlying brain changes (amyloid buildup and other early nerve cell changes) that are not yet detectable. Individuals in this stage are cognitively normal and asymptomatic. In some cases, amyloid buildup can be detected with positron emission tomography (PET) scans and CSF analysis. The NIA and Alzheimer’s Association have proposed three stages within the preclinical stage based on biomarkers, but these stages have not been widely adopted to date. Individuals in stages 1 and 2 may not progress beyond those stages, whereas individuals in stage 3 are more likely to progress to MCI or AD. The stages include (McKhann et al., 2011; Wolk & Dickerson, 2024):

• Stage 1 (asymptomatic amyloidosis): high PET amyloid tracer retention and low CSF beta-amyloid
• Stage 2 (amyloidosis and neurodegeneration): neuronal dysfunction on flurodeoxyglucose-PET (FDG-PET)/functional magnetic resonance imaging (fMRI), high CSF tau, and cortical thinning/hippocampal atrophy on structural MRI (sMRI)
• Stage 3 (amyloidosis and neurodegeneration and subtle cognitive decline): evidence of subtle change from baseline cognition, poor performance on more challenging cognitive tests, and does not yet meet the criteria for MCI

The second stage is marked by 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 baseline cognition and impairment of one or more cognitive functions, but the preserved ability to function independently in daily life, and the absence of dementia. The NIA and Alzheimer’s Association proposed the following criteria for the diagnosis of MCI due to AD (McKhann et al., 2011; Wolk & Dickerson, 2024):

• a concern about cognition reported by the patient, informant, or HCP
• objective evidence of impairment in one or more cognitive domains that is not explained by age or education level
• preservation of independence in functional abilities
• impairments do not meet the criteria for dementia

MCI can also occur as a prodrome to non-neurodegenerative conditions, including depression or medication effects. The specific designation of MCI due to AD is used when a biomarker associated with AD is present. Individuals with MCI may or may not progress to AD, with a progression rate of approximately 10%–15% annually. In a cohort study, researchers found that those individuals with MCI and biomarker presence (amyloid and neuronal injury markers) have a 60% rate of progression over 3 years compared to only 12% of those with MCI without biomarkers (McKhann et al., 2011; Wolk & Dickerson, 2024).

Finally, the third stage is AD. 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. Dementia due to AD must involve at least two of the following domains: the ability to acquire/retain new information, reasoning/judgment/handling of complex tasks, visuospatial abilities, language functions, or changes in personality/behavior. Since AD follows a progressive disease continuum, this third stage (i.e., AD) can be further broken down into mild, moderate, and severe. During the mild stage, a person may still function independently, and symptoms may not be widely apparent. They can include difficulty coming up with the right word; remembering names; losing or misplacing items; and difficulty planning, organizing, and performing tasks in social settings. The moderate stage of AD is typically the longest. Moderate AD can include symptoms such as forgetfulness, being moody or withdrawn, confusion about where they are or what day it is, difficulty controlling their bladder and bowels, changes in sleep patterns, wandering, and personality or behavioral changes. Late AD is the final stage and has the most severe symptoms. During this stage, individuals lose the ability to respond to their environment, carry on a conversation, and control movement. These individuals have significant personality changes and difficulty communicating, along with vulnerability to infections and the loss of physical functions such as walking, sitting, and swallowing (Alzheimer’s Association, n.d.-d; McKhann et al., 2011; NIA, 2025b; Porsteinsson et al., 2021; Wolk & Dickerson, 2024).

Behavioral and psychological symptoms (BPSD) affect up to 90% of patients with moderate to severe AD. BPSD includes depression, hallucinations, agitation, aggression, wandering, and “sundowning” (i.e., worsening cognition and behavioral symptoms later in the afternoon/evening). BPSD contributes to weight loss, falls, infection, incontinence, and caregiver stress and burnout, often leading to the patient requiring a higher level of care. Patients with dementia with new-onset BPSD should undergo a medical evaluation to rule out pain, constipation, infection, vision/hearing loss, depression, sleep disorders, and adverse medication effects. If a specific trigger in their environment (such as overstimulation, a medication, or a problem with a particular caregiver) can be identified, they should be removed if possible (Huang, 2026; Press, 2025).

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; McKhann et al., 2011; Wolk & Dickerson, 2024). The criteria for probable AD include the presence of dementia and the following characteristics:

• a decline in baseline functioning
• not explained by delirium or a major psychiatric disorder
• interference with the ability to function at work or in daily activities
• cognitive impairment established by history taking from the patient and knowledgeable informant, and objective mental status examination or neuropsychological testing
• cognitive impairment, including a minimum of two of the following
  • impaired reasoning or poor judgment
  • impaired visuospatial abilities
  • changes in personality, behavior, or comportment
  • impaired ability to acquire and remember new information
  • impaired language functions
• other core clinical criteria:
  • insidious onset
  • progressive worsening
  • initial and most prominent cognitive deficits are one of the following:
    • amnestic presentation (i.e., impairment in learning and recall of new information)
    • nonamnestic presentation (i.e., language [word-finding deficits], visuospatial, or dysexecutive [impairment in reasoning or judgment])
• no evidence of substantial concomitant cerebrovascular disease, Lewy body dementia, frontotemporal dementia, active neurologic or non-neurologic disease, or medication use that could impact cognition (McKhann et al., 2011; Wolk & Dickerson, 2024)

The criteria for possible AD include the following:

• Atypical presentation: Core criteria for probable AD are met in terms of the nature of the cognitive effects; however, there is a rapid onset of impairment or insufficient historical data to support a progressive decline.
• Etiologically mixed presentation: Core criteria for probable AD are met; however, there is evidence of concurrent cerebrovascular disease, features of Lewy bodies, but not the diagnosis, or another neurologic or medical comorbidity or medication that could significantly impact cognition (McKhann et al., 2011; Wolk & Dickerson, 2024).

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) recognizes that memory might not be the first cognitive domain to be impaired in dementia, introducing the concept of major neurocognitive disorder. Less severe cognitive impairment may be diagnosed as a mild neurocognitive disorder; this closely resembles MCI but with less impairment in daily functioning (American Psychiatric Association [APA], 2022). The DSM-5-TR criteria for major neurocognitive disorder due to AD:

A. evidence of significant decline from a previous level of performance in one or more cognitive domains

• learning and memory
• executive functioning
• complex attention
• social cognition
• language
• perceptual-motor

B. cognitive deficits interfere with independence in everyday activities (at a minimum, assistance is required for complex IADLs, such as managing medications or paying bills)

C. cognitive deficits do not occur exclusively in the context of a delirium

D. cognitive deficits are not better explained by another mental disorder (e.g., schizophrenia, depression)

E. there is an insidious onset and gradual progression of impairment in at least two cognitive domains

F. either of the following

• evidence of a causative AD 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
  • steadily progressive, gradual decline in cognition, without extended plateaus
  • no evidence of mixed etiology (i.e., absence of other neurodegenerative disorders or cerebrovascular disease or another mental, systemic, or neurologic condition likely contributing to cognitive decline; APA, 2022)

There are various differential diagnoses that HCPs should consider and rule out when confronted with a patient with MCI before diagnosing AD. They include:

• medication-related cognitive changes
• depression: consider the Geriatric Depression Scale with a cutoff score of 6
• delirium related to infection or other causes
• thyroid dysfunction
• B12 deficiency: assess for peripheral neuropathy symptoms
• vascular dementia/stroke: assess for gait disturbance, sensory changes, weakness
• Parkinson’s disease: assess for speech impediment/gait disturbance
• Lewy body dementia: assess for hallucinations
• frontotemporal dementia: assess for gait disturbance, personality changes
• normal pressure hydrocephalus: assess for gait disturbance
• substance or alcohol use disorder
• Wernicke-Korsakoff’s syndrome (thiamine deficiency typically related to alcoholism)
• Creutzfeldt-Jakob’s disease
• tumor: morning headaches or lateralizing signs on cranial nerve exam
• syphilis or HIV-related dementia
• sleep deprivation: look for a history of sleep apnea or restless leg syndrome (Huang, 2025; Lui & Tsao, 2024; Wolk & Dickerson, 2024)

These diagnoses can often be ruled out with a complete history and physical exam, which should include a thorough neurologic exam. Clinical criteria are 85% accurate in establishing a diagnosis of AD by eliminating other potential causes of cognitive impairment. This evaluation will help identify delirium (onset over days per weeks, not months per years) and any medication that could be contributing to the cognitive decline. Medications at increased risk for causing cognitive impairment include opioids, anticholinergics, tricyclic antidepressants, benzodiazepines and other hypnotics, muscle relaxants, antihistamines, and antiepileptics. Serum levels of potentially toxic medications such as digoxin (Lanoxin) and antiepileptics should be checked if appropriate. Routine laboratory testing cannot confirm an AD diagnosis but can exclude some contributing secondary causes. Standard laboratory tests recommended by the Alzheimer’s Association include thyroid-stimulating hormone, complete blood count, vitamin B12 and folate levels, complete metabolic panel, fasting glucose, and tests for HIV and/or syphilis. 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; Huang, 2025; Larson, 2025; Lui & Tsao, 2024; Wolk & Dickerson, 2024).

In 2020, CCCDTD5 published its findings regarding the diagnostic criteria and treatment essentials for HCPs. They endorsed all the diagnostic criteria and definitions put forth by the joint efforts of the NIA and Alzheimer’s Association in 2011. They recommend the adoption of the biologic ATN definition of AD proposed in the 2018 NIA and Alzheimer’s Association workgroup for observational and interventional research only (Ismail et al., 2020). The CCDTD5 has made the following recommendations regarding the use of neuroimaging and fluid biomarkers for the diagnosis of AD:

• Anatomic neuroimaging is recommended in most situations, regardless of age, based on specific indications (i.e., onset of cognitive symptoms within the past 2 years, unexpected or unexplained decline in cognition and/or functional status in a person with known AD, recent head trauma, unexplained neurologic manifestations).
• MRI is recommended over computed tomography (CT); if CT is performed, a noncontrast CT is recommended to assess hippocampal atrophy better.
• FDG-PET is recommended for patients who have undergone the recommended baseline structural imaging and who have been evaluated by a cognitive disorder specialist whose underlying pathologic process is still unclear.
• Ordering PET amyloid imaging tests should be limited to dementia experts.
• FDG-PET should be ordered before amyloid imaging based on costs.
• CSF analysis is not routinely recommended, but can be considered in patients with diagnostic uncertainty and onset at an early age (less than 65) to rule out AD.
• CSF analysis can be considered in patients with diagnostic uncertainty and predominance of language, visuospatial, dysexecutive, or behavioral features to rule out AD (Ismail et al., 2020; Larson, 2025).

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, refer to Table 2), the global deterioration scale (GDS, refer to Table 3), and the clinical dementia rating scale (CDR, refer to Table 4). While the FAST evaluates the patient’s functional abilities and ADLs, the GDS focuses more on cognition. Both can monitor a patient’s progress through the disease and assist in making decisions and educating patients and caregivers. The CDR tests memory and performs better when assessing for amnestic MCI, highlighted by memory loss. It is also less effective at detecting very mild dementia (Dementia Care Central, 2025; Mitchell, 2025; Petersen, 2024).

Table 2

Functional Assessment Staging Tool (FAST)

Stage	Patient Condition	Level of Functional Decline	Average Duration of Stage
1	Normal adult	No decline	N/A
2	Normal older adult	Personal awareness of some functional decline	Unknown
3	Early AD	Noticeable deficits in demanding situations	7 years
4	Mild AD	Requires assistance in complicated tasks (i.e., traveling, finances)	2 years
5	Moderate AD	Requires assistance in choosing proper clothing	1.5 years
6	Moderately severe AD	Requires assistance with dressing, toileting, and bathing and experiences urinary and fecal incontinence	3.5–9.5 months
7	Severe AD	Speech ability declines to approximately six intelligible words; progressive loss of ability to walk, sit up, smile, or hold head up	1–1.5 years

(Dementia Care Central, 2025; Mitchell, 2025; Petersen, 2024)

Table 3

Global Deterioration Scale (GDS)

Stage	Signs and Symptoms	Average Duration of Stage
1 (no cognitive decline; no dementia)	Normal function No memory loss	N/A
2 (very mild cognitive decline; no dementia)	Forgets names Misplaces familiar objects Symptoms not evidence to loved ones or HCP	Unknown
3 (mild cognitive decline; No dementia)	Increased forgetfulness Decreased work performance Gets lost frequently Difficulty finding the right words Slight difficulty concentrating Loved ones begin to notice	2–7 years
4 (moderate cognitive decline; early-stage dementia)	Difficulty concentrating or completing tasks Cannot manage finances Forgets recent events Cannot travel alone to new places In denial about symptoms Socialization problems (withdrawn) HCP can detect cognitive problems	2 years
5 (moderately-severe cognitive decline; mid-stage dementia)	Significant memory deficiencies Needs assistance with ADLs Does not know the time and date Does not know where they are Forgets details like address or phone number	1.5 years
6 (severe cognitive decline; mid-stage dementia)	Cannot complete ADLs without assistance Forgets names, recent events, or significant events from the past Difficulty counting down from 10 Incontinence (bladder) Difficulty speaking Personality and emotional changes (i.e., delusions, compulsions, anxiety)	2.5 years
7 (very severe cognitive decline; late-stage dementia)	Cannot speak or communicate Requires assistance with most activities Loss of motor skills Cannot walk	1.5–2.5 years

(Dementia Care Central, 2025; Mitchell, 2025; Petersen, 2024)

Table 4

Clinical Dementia Rating (CDR) Scale

Stage	Description	Average Duration of Stage
CDR-0	No dementia	N/A
CDR-0.5	Very mild dementia slight memory problems some difficulty with time and problem-solving slight impairment of daily life can perform personal care	2–7 years
CDR-1	Mild dementia moderate memory loss that interferes with daily activities moderate difficulty problem-solving cannot function independently outside home difficulty with daily activities and hobbies	2 years
CDR-2	Moderate dementia more profound memory loss, including well-known people and facts disorientation to time and place impaired judgment little to no independent function at home fewer interests	2–4 years
CDR-3	Severe dementia severe memory loss disorientation to time and place no judgment or problem-solving abilities cannot participate in activities outside the home requires help with all tasks of daily living requires help with most personal care frequent incontinence	1–2.5 years

(Dementia Care Central, 2025; Mitchell, 2025; Petersen, 2024)

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 family’s capabilities. Care decisions should be guided by carefully considered overall care goals, such as a desire for all interventions that may prolong life, comfort care only, or something in the middle. This is best done directly by the patient through advance directives whenever possible, relieving the pressure and stress of the proxy decision maker. Without an advance directive, the proxy must do their best to make decisions based on the patient’s best interest (Mitchell, 2025).

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 BPSD. Timely referral to a specialist should be considered when there is uncertainty about the diagnosis of early dementia, when a non-AD is likely, when there is an early onset (less than 65 years of age), and when there is a strong family history. Patients who may be candidates for amyloid-targeted therapies (i.e., those with AD pathology who have MCI) should also be referred to a specialist (Huang, 2025; Press & Buss, 2026). The decision of whether to treat a patient or refer them is a complicated one for many HCPs. The CCCDTD recommends that HCPs refer patients with AD to a specialist in certain circumstances, such as a memory clinic with access to genetic testing and counseling. For example, the special circumstances of EOAD 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 clinic with expertise in this subtype once other causes for the symptoms have been adequately ruled out (Ismail et al., 2020).

Nonpharmacologic treatments for AD and dementia include getting routine medical care to manage comorbidities, regular exercise, and obtaining regular cognitive stimulation. Supplements such as vitamin C, D, E, ginkgo biloba, and omega-3 fatty acids appear to have minimal impact on preventing cognitive decline. A key to the effective management of AD is educating the patient and caregiver(s) regarding the diagnosis and prognosis, encouraging connection with others living with dementia, and focusing on activities that bring purpose to life. Other helpful patient resources include local, regional, and national social support 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). When appropriate and available, patients should be referred to open/enrolling clinical trials (NIA, 2023b; Press & Buss, 2025b).

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 health care and financial. Home safety and driver safety should be routine conversations at each health care visit with someone diagnosed with AD or other dementia to ensure safety measures are in place. HCPs should 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 avoid unfamiliar places and establish a regular daily routine. When needed, patients should be referred to physical therapy for assistance in ambulating safely to limit the risk of falls and occupational therapy for assistance with independent living skills. For patients still working and having difficulty with job performance, reduced hours, a less demanding position, and a consultation with their employer’s human resources department regarding employee assistance programs, family leave, and long-term disability benefits are recommended (NIA, 2025c; Press & Buss, 2025b).

 

Cholinesterase Inhibitors

There are currently various US Food and Drug Administration (FDA)-approved medications. Patients with AD have reduced cerebral content of choline acetyltransferase, which causes a decrease in acetylcholine synthesis and impaired cortical cholinergic function. Cholinesterase inhibitors (ChEIs) function by reversibly binding to and thus inactivating acetylcholinesterase, the enzyme that breaks down acetylcholine at the synaptic cleft. ChEIs commonly used with AD include donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon). Most patients with newly diagnosed AD should be offered a trial of ChEI for symptomatic treatment of cognition and global functioning; however, the degree of benefit is expected to be modest, and they should be discontinued if no benefit is noted or if significant side effects develop. There is no evidence that ChEIs are neuroprotective or have the ability to alter disease trajectory. There is also no evidence that ChEIs should be used for patients with MCI. Donepezil (Aricept) is approved for all stages of AD, available in a tablet and an orally disintegrating tablet (ODT), and dosed once daily, which is a significant advantage. The recommended dose is 5 mg orally daily for 4–6 weeks, then increased to 10 mg daily. Donepezil (Aricept) 23 mg daily may be more effective for moderate to severe AD. Donepezil (Aricept) is also available as a transdermal patch. It is dosed as 1 patch (5 mg/24 hours) transdermally once weekly. After 4–6 weeks, the dose can be increased to 1 patch (10 mg/24 hours) transdermally once weekly. Galantamine (Razadyne) is available in both an immediate-release (IR) tablet or solution and an extended-release (ER) tablet. The recommended dosing for the galantamine (Razadyne) IR is 4 mg orally twice daily with monthly increases of 4 mg to a maintenance dose of 12 mg twice daily. For galantamine (Razadyne) ER, the recommended dose is 8 mg orally daily, with monthly increases of 8 mg to a maintenance dose of 24 mg. It cannot be used in end-stage renal disease or severe liver dysfunction. Rivastigmine (Exelon) is a slow, reversible inhibitor that is available as a capsule or a transdermal patch. The recommended dose of rivastigmine (Exelon) is 1.5 mg orally twice daily, with suggested increases of 1.5 mg every 2–4 weeks to a maintenance dose of 6 mg twice daily. The transdermal patch is dosed at one patch (4.6 mg/24 hours) transdermally once daily, increased monthly to 9.5 mg/24 hours, and then 13.3 mg/24 hours. Benzgalantamine (Zunveyl) was approved in 2024 and comes in an ER tablet. The recommended dosing is 5 mg orally twice daily with monthly increases of 5 mg to a maintenance dose of 15 mg. Galantamine (Razadyne), rivastigmine (Exelon), and benzgalantamine (Zunveyl) are approved for mild to moderate AD. Common adverse effects of ChEIs include nausea, vomiting, poor appetite, and increased frequency of bowel movements. Sleep disturbances are common with donepezil (Aricept). These medications are contraindicated in patients with severe cardiac conduction abnormalities (Huang, 2025; Lui & Tsao, 2024; Press & Buss, 2026).

The CCCDTD5 states that ChEIs have demonstrated efficacy for mild to severe AD and would therefore be an appropriate medication to trial in most patients with AD and patients with mixed pathology (i.e., those with a component of cerebrovascular disease). They concluded that ChEIs may be considered for the treatment of vascular cognitive impairment in selected patients. They found that any differences between the options of ChEIs are primarily based on adverse effect profiles and pharmacokinetics, not efficacy. ChEIs should be tapered and not stopped abruptly (Ismail et al., 2020). They list potential adverse effects of peripheral cholinergic stimulation related to ChEIs as follows:

• increased risk of gastrointestinal (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 (Ismail et al., 2020)

 

N-methyl-d-aspartate Antagonists

Another medication available, memantine (Namenda), functions as an N-methyl-d-aspartate (NMDA) receptor antagonist that regulates glutamate activity. 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. The dose is 5 mg orally daily, increased by 5 mg weekly, to 10 mg twice daily over 4 weeks. The dose should be reduced for patients with renal impairment, or this medication should be avoided. Memantine (Namenda) can be used with a ChEI. Common adverse effects include headache, constipation, confusion, and dizziness. A combination once-daily capsule containing immediate and extended-release components of memantine and donepezil (Namzaric) is available. Memantine (either Namenda or Namzaric) is only approved for moderate to severe AD. These medications modestly improve cognitive function and may delay nursing home placement but should be stopped in the late stages of the disease. When discontinuing memantine (Namenda) or memantine and donepezil (Namzaric), a taper is recommended as a withdrawal reaction can occur. Other medications being studied include high-dose vitamin E (i.e., 1,000 IU orally once or twice a day), selegiline (Eldepryl), NSAIDs, Ginkgo biloba extracts, and statins, but evidence for their effectiveness remains unclear (Huang, 2025; Lui & Tsao, 2024; Press & Buss, 2026).

The CCCDTD5 described a combination treatment using memantine (Namenda) and one of the ChEIs as a treatment for moderate to severe AD. The Canadian group also agreed that medications could and should be stopped when desired by the patient or caregiver, when the patient is nonadherent, when the patient is experiencing intolerable side effects, when comorbidities make continued treatment too risky or futile, when it is ineffective (i.e., 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. They also recommend that if medication is stopped due to perceived ineffectiveness, the patient should be monitored closely for 1–3 months after stopping for a noticeable decline and restarting medication considered in those cases (Ismail et al., 2020).

 

Amyloid-Targeted Therapies

Based on preliminary positive clinical results, the FDA approved aducanumab (Aduhelm) in 2021 using an accelerated approval pathway. In 2024, they discontinued the monoclonal antibody targeted at amyloid plaques because the clinical benefit was insufficient. Amyloid-targeted therapies refer to recombinant monoclonal antibodies directed against amyloid beta plaques. They are highly effective in reducing amyloid plaques on PET imaging and are the first agents that could be disease-modifying instead of symptomatic treatment alone. The efficacy is modest in regard to clinical outcomes, and there are risks for adverse effects. Individuals with MCI or early AD who have documented amyloid pathology (i.e., amyloid PET scan or presence of AD biomarkers in the CSF) are eligible for amyloid-targeted therapy. Two amyloid-targeted therapies are currently approved for use in the United States: lecanemab (Leqembi) and donanemab (Kisunla). Lecanemab is a humanized monoclonal antibody targeting amyloid beta protofibrils. Lecanemab (Leqembi) is administered by a 1-hour intravenous (IV) infusion, dosed at 10 mg/kg every 2 weeks. There is no clear guidance on treatment duration, but treatment should stop if the patient progresses to moderate AD. Donanemab (Kisunla) is an immunoglobulin monoclonal antibody directed against the form of beta-amyloid present in brain amyloid plaques, binding and aiding in plaque removal. Donanemab (Kisunla) is administered every 4 weeks as an IV infusion, starting at 350 mg IV over 30 minutes (month 1), increasing to 700 mg IV over 30 minutes (month 2), to 1,050 mg IV over 30 minutes (month 3), and then to 1,400 mg IV over 30 minutes (month 4 and subsequent months). Treatment duration depends on when amyloid clearance is demonstrated (Huang, 2025; Lui & Tsao, 2024; Press & Buss, 2025a, 2026).

 Patients should be monitored for infusion reactions with each dose of amyloid-targeted therapies, which are observed more frequently with lecanemab (Leqembi) compared to donanemab (Kisunla), 26% versus 9%. Signs and symptoms of an infusion reaction include fever, chills, rash, nausea and vomiting, sweating, dyspnea, hypotension or hypertension, headache, and abdominal or chest pain. Clinicians should assess for symptoms of amyloid-related imaging abnormalities (ARIA; i.e., MRI signal changes of cerebral edema [ARIA-E] and/or microhemorrhage and superficial hemosiderosis [ARIA-H]) at each infusion. ARIA-E is characterized by focal vasogenic edema, which can be mild, moderate, or severe. Most patients are asymptomatic, but some can have fatigue, confusion, headache, falls, dizziness, vision changes, or nausea. ARIA-E will resolve in most patients within a few months; some patients will experience a recurrence if treatment is restarted. ARIA-H manifests as microhemorrhage, which can vary in number and extent, and can occur concurrently with ARIA-E. An MRI should be ordered before doses 5, 7, 14, and 26 to evaluate for ARIA or if a patient shows symptoms of ARIA for lecanemab (Leqembi) and prior to the second, third, fourth, and seventh infusions of donanemab (Kisunla; Huang, 2025; Lui & Tsao, 2024; Press & Buss, 2025a, 2026).

Behavioral and Psychological Symptoms of Dementia

Since many patients with AD experience BPSD, HCPs should be aware of the nonpharmacologic treatments for BPSD, including behavioral changes such as:

• establish and maintain a consistent daily routine
• encourage routine physical activity and optimize nutrition (but include comfort foods)
• incorporate enjoyable activities such as art, music, and spirituality
• allow for regular reminiscing and storytelling
• 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 (Huang, 2026; Press, 2025)

If these modifications do not alleviate the BPSD, then HCPs should consider and evaluate the risks versus benefits of medications. Currently, there are no FDA-approved medications for BPSD, but commonly used off-label medications include antipsychotics, benzodiazepines, antidepressants, and antiseizure medications. For example, there is evidence of benefit from the use of antipsychotics for symptoms of aggression, but there are also significant adverse effects. Seventeen placebo-controlled trials of antipsychotics showed a significant reduction in aggressive behavior at 12 weeks of use but also showed a 1.6- to 1.7-fold increase in mortality, primarily due to infection and cardiovascular causes. This led to an FDA boxed warning that all antipsychotics increase mortality risk 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. Despite these risks, risperidone (Risperdal), olanzapine (Zyprexa), or aripiprazole (Abilify) are listed as potential treatment considerations in patients with AD with severe agitation/aggression and psychosis if there is a risk of harm to self or others. There is insufficient evidence to recommend or discourage the use of quetiapine (Seroquel). Valproate (Depakene, Depacon) should not be considered for this indication due to the risk of toxicity, accelerated brain volume loss, and greater cognitive impairment. Suvorexant (Belsomra) is approved for the treatment of insomnia in patients with mild to moderate AD. It works by blocking the activity of orexin, a chemical messenger involved in the sleep-wake cycle. Side effects can include impaired coordination, worsening depression or suicidal ideation, sleep paralysis, and compromised respiratory function (Huang, 2026; Ismail et al., 2020; Press, 2025).

The 2023 Beers Criteria, published by the American Geriatric Society, suggests avoiding antipsychotics in patients with dementia with behavioral issues unless the patient is a threat to themselves or others, and only after nonpharmacologic treatments have been tried and failed due to the increased risk for stroke and mortality. Benzodiazepines carry significant risks, including depression, confusion, sedation, increased risk of falls/fractures, stroke/cerebral adverse events, sleep disturbance, and delirium. The 2023 Beers Criteria states that strong evidence exists to avoid using benzodiazepines in treating agitation in older adults secondary to the increased risk of falls. The CCCDTD5 states that insufficient evidence supports the use of selective serotonin reuptake inhibitors (SSRIs) or trazodone (Oleptro) for treating agitation in patients with AD. However, they point out that a trial of antidepressant medication could be considered for a major depressive episode, severe dysthymia, or severe emotional lability (American Geriatrics Society Beers Criteria Update Expert Panel, 2023; Ismail et al., 2020).

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 that none of the foregoing 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. Various research studies have found insufficient evidence to support tube feeding in patients with advanced dementia since 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 feedings, 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, 2025).

Infections are another prevalent complication in patients with advanced dementia, especially of the urinary and respiratory tract. In one study, 52%–66% of patients with advanced dementia in a nursing home were prescribed antibiotics in the last 12 months. The 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 should help guide treatment decisions in this instance as well. In the Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia (SPREAD), 75% of suspected infections were treated with antimicrobials. However, less than 50% of all treated infections (and less than 20% of all urinary tract infections [UTIs]) met the appropriate criteria for initiation of antimicrobials. Urinalysis and urine cultures are frequently positive in patients with advanced dementia, and asymptomatic bacteriuria should not be treated (Mitchell, 2025).

For this reason, negative test results can help rule out an infection, but positive results do not necessitate treatment. For example, in a patient with no indwelling catheter, the minimal criteria for initiating antibiotics for a suspected UTI is acute dysuria in a verbal patient. If the patient is nonverbal, the requirements include an elevated temperature of over 100°F (or greater than 2°F above baseline) and at least one of the following: frequency (new or worse), urgency, costovertebral tenderness, hematuria, suprapubic pain, or mental status changes. The minimal criteria for a patient with a catheter would be a fever over 100°F or greater than 2°F above baseline, rigors, or a mental status change. The minimal criteria for a suspected lower respiratory infection are a temperature over 102°F in combination with an elevated respiratory rate above 25 bpm or a new productive cough. In a patient with a temperature lower than 102°F, there must be a new productive cough and one of the following: heart rate above 100 bpm, respiratory rate above 25 bpm, rigors, or a change in mental status. 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, 2025).

Regarding end-of-life care, palliative and/or hospice care referrals should be made when deemed appropriate in patients with advanced AD. A major limitation of enrollment in hospice care is that it requires a life expectancy of 6 months or less. Currently, in order to qualify for hospice care for AD, Medicare requires a rating of 7 on the FAST (refer to Table 2 for details of the FAST scale stages). The patient must have also had a medical complication in the previous year, such as aspiration pneumonia, pyelonephritis or other upper 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 than 10% during the previous 6 months or serum albumin less than 2.5 g/dL). Observational studies of patients with advanced dementia enrolled in hospice care have shown fewer hospitalizations, higher frequency of treatment for pain and dyspnea, and families that are more satisfied with patient care. If referral to a palliative or hospice care specialist is available, these options should be offered and discussed with the patient’s health care proxy (Mitchell, 2025).

Research

The Alzheimer’s Association is the largest nonprofit funder of Alzheimer’s research and is committed to accelerating global efforts to eliminate AD. They currently invest over $450 million in more than 1,200 research projects across 56 countries and 6 continents. Research efforts focus on advancing the understanding of AD and dementia, identifying new treatment strategies, improving care and support for people with AD, and improving knowledge of brain health and disease prevention (Alzheimer’s Association, n.d.-c, n.d.-e). The Alzheimer’s Association is currently funding the NEW IDEAS Study, which seeks to ensure that the results of AD and dementia research represent all racial and ethnic groups. In this study, 4,000 of the projected 7,000 participants will be Black or Hispanic. The researchers will examine brain amyloid PET scans in diverse populations with mild dementia (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. For almost 10 years, the WHO Global Dementia Observatory has collected and organized worldwide data to help researchers across the globe share information and function as a team to work toward a potential solution to AD (WHO, 2021).

The NIH and the NIA lead the research efforts to understand the causes of AD, identify early signs, develop treatments to prevent or delay disease progression, and improve the care for patients living with AD. The NIH invests significant funding in the investigation of new or repurposed drugs to treat or slow the progression of AD. For example, based on the findings of abnormal electrical activity in the brains of people with AD, many studies have evaluated whether the use of antiseizure medications could be effective in AD. In recent years, there has been significant progress in the treatment of early AD, with the approval of specific amyloid-targeting therapies. The NIH is still funding trials to understand how to safely and effectively use the current approved anti-amyloid immunotherapies. Another area where the NIH has provided research funding is the investigation of gene therapies as an innovative way to prevent or treat AD. In addition to pharmacologic treatments, the NIH also supports research to explore the role of nonpharmacologic interventions to reduce the risk factors for AD and improve cognition and memory. These interventions include blood pressure control, hearing aids, multivitamins, and personalized health coaching. NIH-funded research has also focused on the development of newer, less invasive, and less expensive diagnostic tools for AD. In addition, significant advances have been made in the use of biomarkers for the detection and diagnosis of AD (NIA, 2025a).

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