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Introduction   

Dementia is a broad term that describes a significant decline in cognitive abilities that interferes with a person’s daily life [1]. Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for at least two-thirds of dementia cases in individuals aged 65 and older [1]. AD is a neurodegenerative disorder characterized by an insidious onset and progressive impairment of cognitive and behavioral functions, including memory, comprehension, language, attention, reasoning, and judgment [1][2]. Although Alzheimer's disease (AD) itself is not fatal through direct mechanisms, it increases susceptibility to complications that can lead to premature death including aspiration pneumonia which occurs when the disease causes difficulty in swallowing, leading to the inadvertent inhalation of food particles, liquids, or gastric fluids into the lungs [1]. 

In 2022, Alzheimer's disease was the seventh leading cause of death in the United States, according to the Centers for Disease Control and Prevention (CDC) [3]. This is a decrease from its previous position as the sixth leading cause of death before the COVID-19 pandemic, which ranked fourth in 2022 [3]. Alzheimer's disease often appears after the age of 65, known as late-onset AD (LOAD) [3][4]. However, early-onset AD (EOAD), which occurs before age 65, is less common and affects about 5% of patients with AD [4]. EOAD often presents with atypical symptoms and with aggressive progress, leading to delayed diagnosis and a more severe disease course [5]. 

Over the past decade, there have been significant advancements in identifying biomarkers for the early and specific diagnosis of AD. These include neuroimaging markers from amyloid and tau PET scans, as well as cerebrospinal fluid (CSF) and plasma markers such as amyloid, tau, and phospho-tau levels [6]. 

While there is no cure for Alzheimer's disease, treatments are available to manage and alleviate some symptoms. Recent advancements in medication and the discovery of new biomarkers have shown promise in moderating the disease's progression.  

Warning Signs and Symptoms of Alzheimer’s Disease and Other Dementias 

Alzheimer's disease features gradual and progressive neurodegeneration due to neuronal cell death [1][7]. The neurodegenerative process often initiates in the entorhinal cortex, a region within the hippocampus [1][8]. Genetic factors contribute to both early and late-onset AD. Trisomy 21, for example, presents a risk factor for early-onset dementia [9]. Alzheimer's disease (AD) symptoms vary depending on the disease stage, which classifies into distinct levels of cognitive impairment and disability. These stages include the preclinical or presymptomatic stage, mild cognitive impairment, and the dementia stage, further divided into mild, moderate, and severe stages [1][10].  

This staging system differs from the diagnostic criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) [1]. The initial and most common symptom of typical AD includes episodic short-term memory loss [11]. Individuals often struggle to retain added information while their long-term memories remain intact. As the disease progresses, impairments in problem-solving, judgment, executive functioning, and organizational skills become evident [11]. Early in the disease, instrumental activities of daily living, such as driving, managing finances, cooking, and planning, suffer [1]. 

As cognitive decline advances, individuals may experience language disorders and impaired visuospatial skills. In the moderate to late stages, neuropsychiatric symptoms like apathy, social withdrawal, disinhibition, agitation, psychosis, and wandering become more prevalent [1][12]. Late-stage symptoms can include difficulty with learned motor tasks (dyspraxia), olfactory dysfunction, sleep disturbances, and extrapyramidal motor signs such as dystonia, akathisia, and Parkinsonian symptoms [1][12]. In the final stages, primitive reflexes, incontinence, and complete dependence on caregivers are common [1][12]. 

AD involves multiple factors and includes many known risk factors. Age serves as the most significant factor, with advancing age as the primary contributor. The prevalence of AD doubles with every 5-year increase in age starting from age 65 [13]. Cardiovascular diseases (CVD) increase the risk of developing AD and contribute to dementia caused by strokes or vascular dementia [14]. Recognizing CVD as a modifiable risk factor for AD has become more common. 

Obesity and diabetes are also important modifiable risk factors for AD [15]. Obesity can impair glucose tolerance and increase the risk of developing type II diabetes [1]. Chronic hyperglycemia can lead to cognitive impairment by promoting the accumulation of beta-amyloid (A-beta) and neuroinflammation [1][16]. Obesity further amplifies the risk by triggering the release of pro-inflammatory cytokines and promoting insulin resistance [16]. 

Other potential risk factors for AD include traumatic head injury, depression, cardiovascular and cerebrovascular disease, higher parental age at birth, smoking, family history of dementia, increased homocysteine levels, and the presence of the APOE e4 allele [1][17]. Having a first-degree relative with AD increases the risk of developing the disease by 10% to 30% [18]. Individuals with two or more siblings with late-onset AD face a threefold higher risk than the general population [1][19]. 

Importance of Early Detection, Diagnosis, and Communication for Memory Concerns 

Early detection and diagnosis of Alzheimer's disease (AD) are critical for effective management and care planning [20]. A thorough history-taking and comprehensive physical examination are fundamental in diagnosing AD. Gathering information from family and caregivers is also vital, as patients may lack insight into their condition. Evaluating a client's functional abilities, encompassing both basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs), offers import information about their cognitive and functional status. IADLs require advanced planning and cognitive skills, including tasks like shopping, managing finances, filing taxes, preparing meals, and housekeeping. 

In addition to medical history, inquire about the patient's social history, including alcohol use and any history of street drug use. These factors can influence cognitive function and require consideration in the diagnostic process. 

Conduct a physical exam, including a neurological exam and mental status assessment, to evaluate the AD stage and rule out other conditions. The neurological exam in AD may appear normal except for anosmia. Anosmia also occurs in patients with Parkinson's disease, dementia with Lewy bodies, and traumatic brain injury (TBI) with or without dementia, but not in individuals with vascular cognitive impairment (VCI) or depression [1][21]. 

Perform and document cognitive assessments such as the Mini-Mental Status Exam (MMSE) or the Montreal Cognitive Assessment Exam (MOCA). The MOCA evaluates patients with mild cognitive impairment more effectively than the MMSE [22][23]. Another cognitive screening test, the Mini-Cog exam, involves a clock drawing test and a three-item recall [24]. The results of the Mini-Cog remain consistent regardless of the individual's level of education.  

In the advanced stages of AD, patients may exhibit more focal neurological signs, including apraxia, aphasia, frontal release signs, and primitive reflexes [1] [25]. As the disease progresses, patients may become mute and unresponsive to verbal requests, leading to increased dependence on caregivers and becoming confined to bed and entering a persistent vegetative state. 

During a mental status examination, evaluating multiple cognitive domains is important to determine the extent of cognitive decline in Alzheimer's Disease (AD) [1]. These domains encompass concentration, attention, recent and remote memory, language abilities, visuospatial skills, praxis, and executive functions [1][26]. Regular follow-up appointments for individuals with AD should incorporate a comprehensive mental status examination to monitor disease progression and the emergence of neuropsychiatric symptoms. 

Effective communication techniques are essential when discussing memory concerns with the patient and their caregiver. Clear, empathetic communication helps in building trust and ensuring that the patient and caregiver understand the diagnosis, treatment options, and care plans. This approach fosters a supportive environment, enabling better management of the disease and improving the quality of life for both the patient and the caregiver. 

Tools for Assessing a Patient’s Cognition 

Cognitive assessment uses various tools to evaluate various aspects of cognitive function, which diagnose and manage conditions such as Alzheimer's disease (AD) and other dementias. These tools build a clinical understanding of care needs through ongoing interactions with the patient and caregiver. Customize the choice of assessment tools to fit clinician preferences, practice composition, workflows, and clinical goals. Here are some commonly used tools 

• Mini-Mental State Examination (MMSE): used for a quick assessment of cognitive function. 

• Montreal Cognitive Assessment (MOCA): More sensitive than the MMSE for detecting mild cognitive impairment. 

• Mini-Cog: Involves a clock drawing test and three-item recall, useful in primary care settings. 

• Functional Assessment Staging Test (FAST): For staging dementia. 

• Clinical Dementia Rating (CDR): For staging and evaluating dementia severity. 

Use these tools alongside other diagnostic procedures such as blood tests, imaging (CT, MRI), and neuropsychological testing to evaluate  

Documentation Requirements 

Documentation of cognitive-relevant history should include factors contributing to cognitive impairment, such as psychoactive medications, chronic pain syndromes, infection, depression, and other brain diseases [28]. Medical decision-making documentation should cover the current and progression of the patient’s disease and the need for referrals to rehabilitative, social, legal, financial, or community services. 

Patients without a firm diagnosis need documentation confirming cognitive impairment and a narrative history supporting the suspicion of potential cognitive impairment [28]. Use standardized tools for cognitive assessments and keep the full instrument raw scoring and results available for Medicare Administrative Contractor review if requested. 

Required Tools and Assessments 

Document the following standardized tools within the medical record: 

• Cognitive assessment tools: Mini-Cog©, GPCOG, Short Montreal Cognitive Assessment (s-MoCA) [31]. 

• Functional assessment tools: Katz Index of Independence in Activities of Daily Living, Lawton-Brody Instrumental Activities of Daily Living Scale (IADL) [32]. 

• Dementia staging tools: Functional Assessment Staging Test (FAST), Clinical Dementia Rating (CDR® Dementia Staging Instrument), Dementia Severity Rating Scale (DSRS), Global Deterioration Score (GDS) [33]. 

• Neuropsychiatric assessment tools: Neuropsychiatric Inventory Questionnaire (NPI-Q), BEHAV5+©, Patient Health Questionnaire-2 (PHQ-2) [34]. 

Additional Documentation 

Additional documentation of cognitive-relevant history should include: 

• Medication reconciliation 

• Evaluation of home and vehicle safety 

• Identification of social supports and caregivers 

• Advance care planning and palliative care needs 

Background and Introduction to CPT® Code 99483 

The Alzheimer’s Association advocates for Medicare reimbursement for services to improve detection, diagnosis, and care planning for patients with Alzheimer's disease and related dementias (ADRD). This advocacy led to the approval of Medicare procedure code G0505 in January 2017, later replaced by CPT code 99483 in January 2018 [35]. CPT code 99483 reimburses physicians and eligible billing practitioners for a clinical visit that produces a written care plan [35]. 

Who Is Eligible for Comprehensive Care Planning Services? 

Provide cognitive assessment and care plan services under CPT code 99483 when a comprehensive evaluation of a new or existing patient with signs or symptoms of cognitive impairment is necessary [35]. This evaluation aims to establish or confirm a diagnosis, etiology, and severity of the condition. If any required elements are missing or unnecessary, use the appropriate evaluation and management (E/M) code instead. 

Requirements for CPT Code 99483 

To bill under CPT code 99483, perform the following service elements [28]: 

1. Cognition-focused evaluation, including a pertinent history and examination  
2. Medical decision-making of moderate or high complexity  
3. Functional assessment (e.g., this includes basic and instrumental activities of daily living as well as decision-making capacity).   
4. Use of standardized instruments to stage dementia (e.g., Functional Assessment Staging Test [FAST], Clinical Dementia Rating [CDR]) [30].  
5. Medication reconciliation and review for high-risk medications  
6. Evaluation for neuropsychiatric and behavioral symptoms, including depression, using standardized instruments  
7. Assessment of safety, both within the home environment and in other settings, including considerations for motor vehicle operation if relevant.  
8. Identification of caregivers, their knowledge, needs, social supports, and willingness to take on caregiving tasks  
9. Development and periodic updating of an Advance Care Plan  
10. Develop a comprehensive written care plan that addresses neuropsychiatric and neurocognitive symptoms, outlines functional limitations, and includes referrals to community resources. Document and share this plan with the client and/or caregiver. 

This service involves 50 minutes of face-to-face time with the patient and/or family or caregiver. Do not report cognitive assessment and care plan services if any essential elements are either absent or deemed unnecessary. Instead, use the appropriate evaluation and management (E/M) code [28]. 

Assessment Settings and Documentation 

Evaluate the first nine assessment elements of CPT code 99483 during the care planning visit or across multiple visits using billing codes (often E/M codes) [36]. Include results of assessments conducted before the care plan visit if they remain valid or update them at the time of care planning. Complete assessments that require a care partner or caregiver before the clinical visit and provide them to the clinician for the care plan. 

Cognitive Assessment and Care Planning Billing Codes 

Use Current Procedural Terminology (CPT) code 99483 for a clinical visit that assesses cognitive impairment and establishes a care plan for patients with dementia or other cognitive impairments, including Alzheimer's disease [27][28]. This code applies to patients at any stage of impairment and once every 180 days billed to the insurance company.  

Additional CPT codes related to cognitive assessment and care planning [27][28]: 

• 99324–99337: Home visits for new patients 

• 99341–99350: Home visits for established patients 

• 99366–99368: Medical team conferences 

• 99497: Advanced care planning for the first 30 minutes 

• 97129, 97130: Cognitive functioning intervention services 

Screening and Billing for Cognitive Assessment 

Medicare Annual Wellness Visits (AWV) require screening for cognitive impairment [29]. Identify cognitive impairment during routine visits through direct observation or information from the patient, family, friends, caregivers, and others. Develop a cognitive assessment and care plan during a separate visit. 

Bill CPT code 99483 apart from the annual wellness visit due to the time and medical decision-making [28]. If providing both services at the same visit, use a -25 modifier [28]. 

Eligible Providers and Settings 

Any healthcare professional qualified to report Evaluation and Management (E/M) services can offer this service, including physicians (MD and DO), nurse practitioners (NP), clinical nurse specialists (CNS), certified nurse midwives (CNM), and physician assistants (PA) [28]. Practitioners must provide documentation substantiating a moderate-to-elevated level of complexity in their medical decision-making, following E/M guidelines [28]. Conduct care planning visits in the office, other outpatient settings, home, domiciliary, rest home settings, or via telehealth. Even when using telehealth, include all required service elements for CPT 99483 [36]. 

Utilizing a Care Plan Template 

The required elements for this service may benefit from a standardized care plan template. This template can simplify communication and track patient care and outcomes but must allow for narrative unique to the patient. Discuss and give the written care plan to the patient and/or family or caregiver and document this face-to-face conversation in the clinical note. Share the care plan with other providers involved in the patient's care to ensure continuity and coordination. 

Frequency of Service and Auditing 

A single physician or other qualified health care professional reports CPT code 99483 no more than once every 180 days [28]. Revise the care plan at intervals and whenever the patient’s clinical or caregiving status changes. Ensure that revisions to reports exclude any service elements of CPT 99483 when billed through alternative E/M codes, such as those for chronic care management or non-face-to-face consultation [28][36]. 

The Alzheimer's Association's Cognitive Impairment Care Planning Toolkit is a valuable resource for practitioners, providing comprehensive guidance on creating effective care plans for patients with cognitive impairment. 

Current Treatments Available to the Patient 

The primary approach to treatment manages symptoms of Alzheimer's disease (AD). Two categories of drugs treat AD: cholinesterase inhibitors and partial N-methyl D-aspartate (NMDA) antagonists [1]. 

Cholinesterase Inhibitors 

Cholinesterase inhibitors work by increasing the levels of acetylcholine, a neurotransmitter involved in learning, memory, and cognitive functions [1][37]. Three drugs in this category have received FDA approval for treating AD [1][37][38]: 

• Donepezil: 

• Preferred medication 

• Used in AD with mild dementia 

• Rapid and reversible inhibitor of acetylcholinesterase 

• Administered once daily in the evening 

• Rivastigmine: 

• Used in mild cognitive impairment (MCI) and mild dementia stages 

• Slow, reversible inhibitor of acetylcholinesterase and butyrylcholinesterase 

• Available in oral and transdermal formulations 

• Galantamine: 

• Approved for MCI and mild dementia stages 

• Rapid, reversible inhibitor of acetylcholinesterase 

• Available as a twice-daily tablet or once-daily extended-release capsule 

• Not suitable for individuals with end-stage renal disease or severe liver dysfunction 

Common side effects of cholinesterase inhibitors include gastrointestinal symptoms such as nausea, vomiting, and diarrhea [37]. They may also cause bradycardia, cardiac conduction defects, and syncope due to increased vagal tone [37]. These medications are contraindicated in patients with severe cardiac conduction abnormalities [37]. 

Partial N-Methyl D-Aspartate (NMDA) Antagonist: Memantine 

Memantine acts as a partial NMDA antagonist that blocks NMDA receptors and slows intracellular calcium accumulation [39]. The FDA has approved it for the treatment of moderate to severe Alzheimer's disease. Side effects may include dizziness, body aches, headaches, and constipation [39]. Combine memantine with cholinesterase inhibitors like donepezil, rivastigmine, or galantamine in individuals with moderate to severe AD [39]. 

Disease-Modifying Therapies for Alzheimer’s Disease 

AD treatment managed symptoms. However, understanding AD's pathophysiology and improving diagnostic testing led to new disease-modifying therapies. These therapies target the disease's mechanisms, even in preclinical and presymptomatic stages. 

Recent Therapy Approvals 

• Aducanumab [40]: 

• FDA accelerated approval in June 2020 

• Shown to reduce amyloid-beta plaque in the brain 

• Did not meet the primary phase III trial endpoint of clinical improvement 

• Lecanemab [41]: 

• FDA accelerated approval in January 2023 

• Reduced amyloid-beta burden in the brain 

• Phase III trial showed a 27% slowing of disease progression 

• Donanemab [42]: 

• Expected FDA approval in 2023 

• Reduced amyloid-beta burden in the brain 

• Slowed cognitive decline by 35% 

Amyloid-Related Imaging Abnormalities (ARIA) 

ARIA results from an immune response to amyloid-targeting therapies, causing capillary leakage and hemorrhages in cerebral vascular walls [43]. Two types exist: ARIA edema (ARIA-E) and ARIA hemorrhage (ARIA-H). Key risk factors for developing ARIA include the apolipoprotein E4 allele and cerebral amyloid angiopathy findings in brain MRI [43]. 

Other Management Strategies in Alzheimer’s Disease 

Manage symptoms such as anxiety, depression, and psychosis in the mid to late stages of the disease. Avoid tricyclic antidepressants due to their anticholinergic effects, which worsen cognitive impairment [44]. Use antipsychotic medications with caution for acute agitation when other interventions have failed, and the patient's or caregiver's safety is at risk. Try SSRIs like citalopram and anticholinesterases like donepezil before considering antipsychotics. 

Prefer second-generation antipsychotics over first-generation antipsychotics due to their safer profile and fewer extrapyramidal side effects [45]. Brexpiprazole, approved by the FDA in May 2023 for treating agitation associated with dementia due to AD, serves as an example. Use the lowest effective dose when prescribing antipsychotics [46]. Avoid benzodiazepines as they worsen delirium and agitation [47]. 

Non-Pharmacological Interventions 

• Behavioral Strategies: Establishing a familiar and secure environment is essential. This includes addressing personal comfort needs, offering security objects, redirecting attention when necessary, removing hazardous items, and avoiding confrontational situations. 

• Sleep Disturbances: Addressing mild sleep disturbances through non-pharmacological strategies such as exposure to sunlight, daytime exercise, and establishing a bedtime routine. 

• Exercise: Regular aerobic exercise slows the progression of AD. 

Conclusion

Alzheimer's disease (AD) is the prevalent form of dementia, impacting cognitive and behavioral functions, and is a leading cause of death among the elderly [1]. AD presents with symptoms that progress from mild memory loss to severe cognitive and functional decline [1]. Early detection and diagnosis are critical for effective management, involving a thorough assessment of cognitive and functional abilities [48]. While there is no cure for AD, symptomatic treatments such as cholinesterase inhibitors and NMDA antagonists can help manage symptoms, and recent advancements in disease-modifying therapies offer new hope for slowing disease progression [49].  

Comprehensive care planning, including regular cognitive assessments and tailored interventions, is essential for optimizing patient outcomes and supporting caregivers. Regular follow-ups and a multidisciplinary approach to treatment, incorporating both pharmacological and non-pharmacological strategies, can improve the quality of life for individuals with AD and their families. 

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