Discover innovative integrative therapies for cognitive decline aimed at promoting mental agility and supporting brain health.

Navigating Dementia Care: An Integrative Approach from Diagnosis to Advanced Therapies

Hello, and welcome. I am Dr. Alex Jimenez, and I am honored to guide you through this educational journey into the complex and rapidly evolving world of dementia, with a specific focus on Alzheimer’s disease. As a Doctor of Chiropractic, Advanced Practice Registered Nurse, and a Board-Certified Family Nurse Practitioner with certifications in Functional Medicine, I have dedicated my career to understanding and treating complex chronic conditions from an integrative perspective. My credentials include DC, APRN, FNP-BC, CFMP, IFMCP, ATN, and CCST.

In our practice, Injury Medical Clinic PA, we believe in a multidisciplinary approach to patient care. This is why I am proud to work alongside our Medical Director and Collaborative Physician, Dr. Maria Guadalupe Cardenas, MD. Dr. Cardenas is Board Certified in Internal Medicine (NPI #1164426749, Texas MD License #J2933) and brings over 40 years of invaluable experience as an internist. Her medical oversight and collaborative expertise are fundamental to our integrative model, ensuring our patients receive comprehensive, evidence-based care that bridges traditional medicine and innovative therapies. Together, our team integrates chiropractic care, medical oversight, functional medicine, personal injury rehabilitation, and other related services to provide a holistic and patient-centered treatment experience.

This post will delve into the latest findings from leading researchers, presenting their work through the lens of modern, evidence-based research methods. We will explore the physiological underpinnings of dementia, discuss current diagnostic and treatment strategies, and examine emerging therapies reshaping the landscape of memory care. My goal is to make this complex information accessible and to illuminate how an integrative approach, including chiropractic care, can play a vital role in supporting individuals with cognitive decline.

Abstract

This educational article provides a comprehensive overview of the evaluation and pharmacological management of dementia, with a primary focus on Alzheimer’s disease. Presented from the first-person perspective of Dr. Alex Jimenez, it explores the shift from a purely clinical diagnosis to a more precise biological framework using the A (amyloid), T (tau), and N (neurodegeneration) criteria. The post details the pathological cascade of amyloid and tau proteins, explaining how these changes occur decades before clinical symptoms manifest. It will discuss the clinical implications of co-occurring neuropathologies, such as vascular disease, Lewy body disease, and TDP-43 pathology, highlighting why a single-target treatment approach is often insufficient. We will examine a structured approach to prescribing for both cognitive and neuropsychiatric symptoms, grounded in the latest evidence. The discussion will cover foundational symptomatic treatments, including acetylcholinesterase inhibitors such as donepezil and NMDA receptor antagonists such as memantine, and will analyze their mechanisms of action and clinical data. A significant portion is dedicated to managing neuropsychiatric symptoms (NPS), emphasizing non-pharmacological interventions and the use of pharmacogenetic testing. We also delve into the new era of disease-modifying therapies (DMTs), including Aducanumab, Lecanemab, and Donanemab, explaining their mechanisms, efficacy, appropriate patient selection, and the critical importance of monitoring for amyloid-related imaging abnormalities (ARIA). Furthermore, the article will detail how integrative chiropractic care, combined with medical oversight by Dr. Maria Guadalupe Cardenas, MD, and functional medicine principles, fits within a holistic treatment paradigm for patients with cognitive decline, and will emphasize the role of our multidisciplinary team at Injury Medical Clinic PA in El Paso, Texas.

Understanding the Modern Diagnosis of Alzheimer’s Disease: Beyond Clinical Symptoms

As clinicians, we cannot effectively discuss treatment without first having a solid foundation in diagnosis. The way we diagnose Alzheimer’s disease has undergone a profound transformation over the past decade. Historically, our diagnostic process was based on a constellation of clinical symptoms—how they appeared, how they progressed, and when they began. This approach has been essential, but a deeper biological understanding of the disease is now augmenting it.

The Traditional Clinical Framework

The traditional diagnostic model relied on identifying measurable impairments in key cognitive domains:

• Memory: Specifically, the inability to recall recent events, even with cues or prompts.
• Executive Function: Difficulties with planning, organizing, and multitasking.
• Language: Problems with word-finding or understanding complex sentences.
• Visuospatial Abilities: Challenges with navigation or recognizing objects.
• Behavior: Changes in personality, mood, or social conduct.

Supporting features for a diagnosis of probable Alzheimer’s disease included:

• Insidious Onset: The changes are gradual, and it’s often difficult to pinpoint the exact day they began.
• Progressive Decline: The symptoms worsen over time.
• Advanced Age: Age is the single greatest risk factor for Alzheimer’s disease.

Another interesting concept explored is cognitive reserve and brain perfusion. Researchers have considered that symptoms may only become apparent when brain function, including blood flow (perfusion), drops below a certain critical threshold. This doesn’t change the underlying pathology, but it explains why some individuals can harbor the disease for years without showing obvious signs. They have a “reserve” that allows them to compensate until that reserve is depleted. This is how we used to frame a diagnosis: “dementia most likely due to Alzheimer’s disease,” differentiating it from other causes like vascular dementia or Lewy body dementia based on the clinical picture.

The Biological Revolution: The “Jack Curves” and the Pathological Cascade

While the clinical diagnosis remains crucial, groundbreaking research has given us a window into the biological processes happening in the brain long before symptoms appear. One of the most influential figures in this field is Dr. Clifford Jack, whose work has reshaped our understanding. His research, often visualized as the “Jack curves,” illustrates the sequence and timeline of biomarker changes in Alzheimer’s disease.

The core of this model, first detailed in papers like his 2013 publication, is the understanding that the pathological proteins associated with Alzheimer’s—beta-amyloid and tau—begin to accumulate in the brain 15 to 20 years before a person experiences measurable cognitive impairment.

Here’s a breakdown of the hypothesized sequence:

1. Amyloid Accumulation (The Initiator): The process is thought to begin with the accumulation of beta-amyloid. Initially, this protein exists in a soluble form, but over time, it aggregates into insoluble amyloid plaques. These plaques are toxic to brain cells and are considered the trigger for the subsequent pathological cascade.
2. Tau Propagation (The Executioner): Following the buildup of amyloid, the tau protein misfolds and accumulates within neurons, forming neurofibrillary tangles. Normally, tau helps stabilize the internal structure of brain cells, but in this pathological state, it disrupts cellular function and leads to cell death.
3. Neurodegeneration and Cognitive Decline: The combined effect of amyloid plaques and tau tangles is the widespread death of neurons (neurodegeneration). As a critical mass of brain cells is lost, the brain’s ability to function diminishes. It is only at this later stage, after years of silent destruction, that cognitive symptoms become noticeable and measurable.

This model has two profound takeaways for us as clinicians:

• The Order of Events: Amyloid appears to be the first domino to fall, triggering the tau pathology.
• The Long Preclinical Phase: The disease is active in the brain for nearly two decades before the first signs of memory loss or confusion emerge.

This long preclinical window is both a challenge and an incredible opportunity. It’s a challenge because the damage has already begun by the time we typically make a diagnosis. But it’s an opportunity because it opens the door for early detection and intervention, potentially before irreversible damage occurs.

The ATN Framework: A Biological Definition of Alzheimer’s Disease

Building on the understanding of this pathological timeline, the scientific community has moved toward a biological definition of Alzheimer’s disease. This is formalized in the ATN classification system, another concept championed by Dr. Jack and his colleagues in a 2018 research framework. ATN provides a structured way to diagnose and classify Alzheimer’s based on objective biological markers, rather than just clinical symptoms.

A stands for Amyloid.

T stands for Tau.

N stands for Neurodegeneration.

Let’s explore each component in detail:

“A” for Amyloid

The “A” in ATN signifies the presence of abnormal amyloid pathology. Initially, this was a simple binary “yes” or “no.” Today, we are moving towards quantifying the amount of amyloid burden.

How We Measure Amyloid:

• Cerebrospinal Fluid (CSF) Analysis: A lumbar puncture (spinal tap) allows us to measure the levels of amyloid-beta 42 (A?42) in the CSF. In Alzheimer’s disease, A?42 levels in the CSF are lower than normal because the protein is trapped in the brain as plaques rather than cleared into the CSF.
• Amyloid Positron Emission Tomography (PET) Scans: This is a sophisticated neuroimaging technique where a radioactive tracer that binds to amyloid plaques is injected into the bloodstream. The PET scanner then detects the tracer, creating an image that “lights up” the areas of the brain with significant amyloid accumulation. Both CSF analysis and amyloid PET are FDA-approved and, in specific cases, covered by Medicare under appropriate use criteria.
• Blood-Based Biomarkers: This is the most exciting and recent development. We now have blood tests that can measure amyloid levels with remarkable accuracy (e.g., A?42/A?40 ratio). While not yet considered the gold standard for a definitive diagnosis, as with PET or CSF, these tests are transforming clinical practice. They are less invasive, less expensive, and highly effective screening tools for identifying individuals who may need more definitive testing.

“T” for Tau

The “T” in ATN represents the presence of abnormal tau pathology, specifically the neurofibrillary tangles.

How We Measure Tau:

• Cerebrospinal Fluid (CSF) Analysis: We can measure phosphorylated tau (p-tau) levels in CSF. Unlike amyloid, p-tau levels are elevated in the CSF of individuals with Alzheimer’s, as it is released from dying and damaged neurons.
• Tau Positron Emission Tomography (PET) Scans: Similar to amyloid PET, there are specific tracers that bind to tau tangles, allowing us to visualize their location and density in the brain. This is particularly valuable because the spread of tau tangles correlates more closely with the severity of cognitive symptoms than amyloid plaques do.
• Blood-Based Biomarkers: Blood tests for specific forms of p-tau (like p-tau181 and p-tau217) are also becoming available. These have shown incredible promise, not just for detecting tau pathology but also as highly accurate proxies for identifying amyloid positivity. They are rapidly being integrated into research and clinical settings.

“N” for Neurodegeneration

The “N” in ATN refers to evidence of neuronal injury or death. This is the downstream consequence of the amyloid and tau pathology.

How We Measure Neurodegeneration:

• Structural Neuroimaging: An MRI (Magnetic Resonance Imaging) is the preferred method here. It can reveal brain atrophy (shrinkage), particularly in key areas like the hippocampus, which is critical for memory formation. While a CT scan can also show atrophy, MRI provides much greater detail. However, it’s important to note that some degree of cerebral atrophy is common with normal aging, so findings like “atrophy greater than expected for age” are nonspecific. MRIs can also show evidence of microvascular changes (small vessel disease), which often co-exists with Alzheimer’s pathology.
• FDG-PET Scans: A Fluorodeoxyglucose (FDG) PET scan measures glucose metabolism in the brain. In Alzheimer’s disease, characteristic patterns of reduced metabolism (hypometabolism) are evident in specific brain regions, indicating that neurons are either dead or dysfunctional.
• Emerging Blood Tests: Researchers are developing blood tests for markers of neuronal death, such as Neurofilament light chain (NfL) and Glial fibrillary acidic protein (GFAP). NfL is a protein released from damaged axons, and its levels rise in various neurodegenerative conditions, not just Alzheimer’s. GFAP is a marker of astrocyte activation, a component of the inflammatory response to neuronal injury. While not yet standard clinical tools, these markers hold future promise for tracking disease progression.

Integrating the ATN Framework into Clinical Practice

The ATN framework allows us to move from a diagnosis of “probable Alzheimer’s” to a biologically confirmed diagnosis. A patient’s ATN profile might look something like this: A+ T+ N+, meaning they have evidence of amyloid, tau, and neurodegeneration, confirming a diagnosis of Alzheimer’s disease along the full continuum.

However, a crucial point to emphasize is that current recommendations advise against biomarker testing in asymptomatic individuals. We are not yet at a stage where we should be screening the general population with these blood tests. The reason is complex. A person can have elevated amyloid levels (A+) but never develop symptoms of dementia. This could be due to other age-related changes or individual resilience. A positive biomarker test in a healthy person could cause significant anxiety and has uncertain prognostic value. Therefore, the current consensus is to use these pathological markers to confirm the underlying cause of disease in individuals who are already presenting with clinical symptoms, whether it’s Mild Cognitive Impairment (MCI) or dementia.

Mild Cognitive Impairment (MCI) is the stage where there are objective, measurable cognitive changes, but the individual is still able to perform their daily activities independently. In dementia, the cognitive impairment is severe enough to interfere with their ability to function independently in daily life. The ATN framework helps us determine if the MCI or dementia is “due to Alzheimer’s disease.”

The Complexity of the Aging Brain: Co-Occurring Neuropathologies

As we gain the ability to look at the brain with greater precision, we are uncovering a fundamental truth: the aging brain is complex, and it rarely suffers from just one problem. Alzheimer’s disease often does not exist in a vacuum. I often explain to my patients and their families that the brain doesn’t have to pick just one pathology. This concept is powerfully illustrated by a recent landmark study published in The Lancet Neurology in 2023. Researchers pooled data from six large, community-based autopsy studies to examine how frequently different neuropathologies co-occur.

The findings are a game-changer for how we think about dementia. The study looked at several key pathologies:

• Amyloid Plaques: The hallmark of Alzheimer’s disease.
• Tau Tangles: The other hallmark of Alzheimer’s, measured by Braak staging for severity.
• Cerebrovascular Disease: Evidence of microinfarcts and macroinfarcts (strokes), which are associated with vascular dementia.
• Lewy Bodies: Abnormal protein aggregates (alpha-synuclein) that are the hallmark of Lewy body dementia and Parkinson’s disease dementia.
• LATE-NC (Limbic-predominant Age-related TDP-43 Encephalopathy): A more recently identified pathology involving the TDP-43 protein, often seen in the oldest-old and mimicking Alzheimer’s symptoms. It can also be associated with frontotemporal dementia.

The Rule, Not the Exception: Mixed Pathology

The study organized individuals into groups based on the number of pathologies found in their brains at autopsy. What they found was staggering.

• Single Pathology: The group of individuals who had only one type of pathology was relatively small. For instance, some had only amyloid, some only tau, and some only vascular changes.
• Multiple Pathologies: The largest groups were those with two, three, or even more co-occurring pathologies. The most common combination, as expected, was amyloid and tau together. However, it was also extremely common to find a third or fourth pathology mixed in.

For example, a significant number of individuals had amyloid, tau, and vascular disease. Another large group had amyloid, tau, and Lewy bodies. I see this combination frequently in my practice: patients who have positive biomarkers for Alzheimer’s disease (A+ T+) but also present with symptoms suggestive of Lewy body dementia, such as visual hallucinations or fluctuations in cognition. The autopsy data confirm that both can indeed be true.

Another fascinating group is those who present with symptoms of Frontotemporal Dementia (FTD)—such as changes in personality and behavior—but also test positive for Alzheimer’s biomarkers. The study showed a cohort with amyloid, tau, and the TDP-43 pathology associated with FTD. Again, both can be true.

Clinical Implications of Mixed Pathology

This reality of mixed pathology has profound implications for treatment. It helps explain why treatments targeting only a single pathway (e.g., only amyloid) may not be a silver bullet. If a patient’s symptoms are being driven by a combination of Alzheimer’s pathology, vascular damage, and Lewy bodies, a therapy that only addresses the amyloid component will likely have a limited effect.

This reinforces the need for a comprehensive, multifaceted treatment approach. Our strategy must be based on the patient’s full clinical picture and symptom expression. We must ask: what is the most pressing and distressing symptom for this patient and their family right now? Is it memory loss? Is it behavioral agitation? Is it a gait disturbance? Our treatment plan should be tailored to address these dominant symptoms, while also considering all the underlying pathological contributors.

Furthermore, this complexity highlights the importance of addressing non-neuropathological factors that can exacerbate symptoms. These include:

• Inflammation: Chronic inflammation is a key driver of neurodegeneration.
• Metabolic Health: Conditions such as insulin resistance and diabetes are strongly linked to cognitive decline.
• Vascular Health: High blood pressure, high cholesterol, and atherosclerosis all impact brain health.
• Gut Health: The gut-brain axis is a critical area of research, with gut dysbiosis linked to neuroinflammation.

This is precisely where an integrative approach becomes so vital. We can’t just prescribe a single medication and expect it to solve a problem with multiple, interacting causes. We need to look at the whole person.

The Role of Integrative Chiropractic Care in a Multidisciplinary Dementia Clinic

At Injury Medical Clinic PA, our model is built on the principle of collaboration. As a Chiropractor and Family Nurse Practitioner, I work hand in hand with our Medical Director, Dr. Maria Cardenas, an experienced Internist. This multidisciplinary structure allows us to provide a truly integrative and comprehensive level of care that addresses the multifaceted nature of conditions like dementia.

People often ask, “What does a chiropractor have to do with dementia care?” The answer lies in a modern, evidence-based understanding of chiropractic that goes far beyond simple spinal adjustments for back pain.

Chiropractic Care and Neurological Function

Modern chiropractic care, especially when integrated with functional medicine, focuses on the intricate relationship between the body’s structure (particularly the spine) and the function of the nervous system. The brain does not operate in isolation; it is in constant communication with the body via the spinal cord and peripheral nerves.

Key Principles of Integrative Chiropractic Care:

• Neuro-Structural Optimization: Chiropractic adjustments are not just about “cracking backs.” They are precise interventions designed to restore proper motion and alignment to the spinal joints. Misalignments, or subluxations, can interfere with the flow of nerve signals between the brain and the body. By correcting these, we can help optimize neurological function. Research has shown that spinal manipulation can influence sensorimotor integration in the prefrontal cortex, change brain metabolism, and affect autonomic nervous system function.
• Improving Cerebral Blood Flow: Emerging evidence suggests that cervical spine (neck) manipulation may influence cerebral blood flow and cerebrospinal fluid (CSF) dynamics. Given that reduced brain perfusion contributes to cognitive decline and vascular dementia, optimizing biomechanical function of the cervical spine may be a supportive strategy for maintaining brain health. This is particularly relevant for our patients who have co-occurring cerebrovascular disease.
• Pain Management and Quality of Life: Chronic pain is a significant stressor that can negatively impact cognitive function and worsen behavioral symptoms in dementia. It elevates cortisol, promotes inflammation, and disrupts sleep—all of which are detrimental to brain health. Chiropractic care is a highly effective, non-pharmacological approach to managing musculoskeletal pain, such as back pain, neck pain, and headaches. By reducing a patient’s pain burden, we can improve their overall quality of life, reduce agitation, and potentially improve their cognitive focus.
• Balance and Proprioception: As dementia progresses, individuals often experience problems with balance, coordination, and an increased risk of falls. Proprioception is the body’s ability to sense its position in space. This sense relies heavily on input from receptors in the joints and muscles, particularly those in the spine and extremities. Chiropractic adjustments and rehabilitative exercises can enhance proprioceptive feedback to the brain, improving balance and reducing fall risk. This is a critical safety intervention for our patients.

The Synergy of a Multidisciplinary Team

Our collaborative model allows us to create a holistic treatment plan that addresses the patient from multiple angles.

• Cardenas (Internal Medicine): Provides expert medical oversight, manages comorbidities like hypertension and diabetes, handles complex medication management, and makes referrals to other medical specialists as needed. Her role is essential for ensuring the patient’s overall medical stability and for prescribing and monitoring pharmacological treatments for dementia.
• Jimenez (Chiropractic, Functional Medicine, FNP): My role bridges several domains. As a chiropractor, I focus on the neuro-structural aspects, pain management, and mobility. As a Family Nurse Practitioner and Functional Medicine provider, I conduct comprehensive lifestyle assessments, order advanced diagnostic tests (including functional and nutritional testing), and design personalized plans that address diet, exercise, stress management, sleep optimization, and targeted supplementation to reduce inflammation and support brain health.
• Rehabilitation Team: We also incorporate physical therapists and other rehabilitation specialists who design specific exercise programs to improve strength, mobility, and balance.

By working together, we can address amyloid and tau pathology with conventional medications (under the supervision of Dr. Cardenas), while simultaneously using chiropractic and functional medicine strategies to reduce inflammation, optimize blood flow, manage pain, improve neurological signaling, and support the body’s overall resilience. This comprehensive approach is far more powerful than any single intervention alone, especially in the context of the mixed pathologies we now know are so common.

Pharmacological Management: A Structured Approach for Symptoms

When we approach the pharmacological treatment of dementia, we must divide our strategy into two main categories:

1. Symptomatic Treatments: Medications that help manage the disease’s cognitive and neuropsychiatric symptoms. They do not stop or slow the underlying disease process.
2. Disease-Modifying Therapies (DMTs): These are newer treatments designed to target the disease’s underlying biology (e.g., amyloid) and slow its progression.

Let’s first focus on the symptomatic treatments, as these have been the mainstay of our therapeutic arsenal for many years. Our prescribing decisions must be structured, targeted, and always guided by a careful risk-benefit analysis.

Treating Cognitive Symptoms

The primary neurotransmitter systems implicated in the cognitive symptoms of Alzheimer’s disease are the cholinergic and glutamatergic systems.

• The Cholinergic System: Alzheimer’s disease leads to a significant loss of neurons that produce acetylcholine, a neurotransmitter vital for memory and learning. This deficit contributes directly to memory impairment.
• The Glutamatergic System: Glutamate is the brain’s primary excitatory neurotransmitter. In Alzheimer’s, it is thought that chronic, low-level overstimulation of glutamate receptors (specifically NMDA receptors) by excessive glutamate leads to excitotoxicity—a process in which nerve cells are damaged and killed by overactivation.

Based on these neurotransmitter perturbations, we have two classes of cognitive-enhancing medications:

1. Cholinesterase Inhibitors (ChEIs)

• • Mechanism of Action: These drugs work by blocking the action of acetylcholinesterase, the enzyme that breaks down acetylcholine in the synaptic cleft. By inhibiting this enzyme, they increase the amount of acetylcholine available for neurotransmission, thereby boosting cholinergic function.
  • Examples:

• • • Donepezil (Aricept): Approved for all stages of Alzheimer’s disease.
    • Rivastigmine (Exelon): Approved for mild to moderate Alzheimer’s and also Parkinson’s disease dementia. Available as a patch, which can reduce gastrointestinal side effects.
    • Galantamine (Razadyne): Approved for mild to moderate Alzheimer’s. It has a dual mechanism, also modulating nicotinic receptors to enhance acetylcholine release further.

• • Clinical Use: ChEIs are typically the first-line treatment for the cognitive symptoms of Alzheimer’s disease. While they do not reverse the disease, they can provide a modest, temporary improvement in cognitive function or, more commonly, stabilize symptoms for 6-12 months.
  • Side Effects: The most common side effects are gastrointestinal (nausea, vomiting, diarrhea), due to increased cholinergic activity in the gut. Other potential side effects include bradycardia (slow heart rate), sleep disturbances (vivid dreams), and muscle cramps. Starting at a low dose and titrating up slowly can help mitigate these.

2. NMDA Receptor Antagonist

• • Mechanism of Action: This class of drug works by blocking the NMDA glutamate receptors. The goal is not to block them completely but to reduce the chronic, low-level excitotoxic “noise” caused by excess glutamate, while still allowing normal physiological signaling required for learning and memory.
  • Example:

• • • Memantine (Namenda): Approved for moderate to severe Alzheimer’s disease.

• • Clinical Use: Memantine is often added to a cholinesterase inhibitor in the moderate-to-severe stages of the disease. The combination is more effective than either agent alone in this population. It can help with cognition, function, and, in some cases, behavioral symptoms like agitation.
  • Side Effects: Memantine is generally well-tolerated. The most common side effects can include dizziness, headache, confusion, and constipation.

It is crucial to set realistic expectations with patients and families. These medications are not a cure. The goal is to maximize function and quality of life for as long as possible.

Treating Neuropsychiatric Symptoms (NPS)

Neuropsychiatric symptoms, also known as behavioral and psychological symptoms of dementia (BPSD), are nearly universal in dementia and are often the most challenging and distressing aspects of the disease for both patients and caregivers. These can include:

• Apathy
• Depression
• Anxiety
• Agitation and aggression
• Psychosis (hallucinations and delusions)
• Sleep disturbances

Our approach to managing NPS must always begin with non-pharmacological interventions. Before reaching for a prescription pad, we must first try to understand and address the root cause of the behavior. Is the person in pain? Are they bored? Are they overstimulated? Are they constipated? Is there an underlying infection (like a UTI)? This is the “DICE” approach: Describe, Investigate, Create, Evaluate.

However, when behaviors are severe, persistent, and pose a risk to the patient or others, pharmacological intervention may be necessary. It is critical to note that most medications used for NPS are used off-label, and many carry significant risks, including FDA black box warnings.

Structured Approach to Prescribing for NPS:

1. Identify the Target Symptom: Be specific. Are we treating anxiety, depression, or psychosis? Using a general “calming” agent is poor practice.
2. Start Low, Go Slow: Use the lowest effective dose for the shortest possible time.
3. Monitor for Efficacy and Side Effects: Regularly assess if the medication is working and if it is causing harm.
4. Attempt to Taper: Periodically try to reduce and discontinue the medication if the behavior has resolved.

Classes of Medications Used for NPS:

• Antidepressants (SSRIs): Citalopram, escitalopram, and sertraline are often the first-line choice for treating depression, anxiety, and sometimes agitation in dementia. They are generally safer than other classes.
• Antipsychotics: These are reserved for severe aggression or psychosis that has not responded to other interventions. They carry a black box warning for increased risk of death in elderly patients with dementia. Atypical antipsychotics like risperidone, olanzapine, and quetiapine are used cautiously.
• Mood Stabilizers/Anticonvulsants: Medications such as valproic acid and carbamazepine have been used to treat agitation, but evidence is mixed, and risks are significant. Their use has declined.
• Sleep Aids: Avoid benzodiazepines and “Z-drugs” (e.g., zolpidem) as they increase confusion, fall risk, and can paradoxically worsen agitation. Trazodone at a low dose is a common choice for insomnia. Melatonin can also be helpful.

The decision to use these medications requires a careful and ongoing conversation with the patient (if able) and their family, weighing the potential benefits against the very real risks.

The New Era: Disease-Modifying Therapies (DMTs)

The most significant breakthrough in Alzheimer’s treatment in decades has been the development of disease-modifying therapies (DMTs). These are monoclonal antibodies designed to target and remove the underlying amyloid pathology from the brain.

This represents a monumental shift from purely symptomatic treatment to tackling the root cause of the disease. Two key agents are at the forefront of this new era:

1. Aducanumab (Aduhelm): The first of its class to receive accelerated approval from the FDA in 2021.
2. Lecanemab (Leqembi): Received full FDA approval in 2023 after demonstrating both significant amyloid removal and a modest but statistically significant slowing of cognitive decline.
3. Donanemab: This therapy also demonstrated significant slowing of decline in its Phase 3 trials and is another major player in this new therapeutic landscape.

How Do They Work?

These drugs are laboratory-produced antibodies that are administered via intravenous (IV) infusion. They are designed to bind specifically to different forms of beta-amyloid in the brain. Once bound, they “tag” the amyloid for removal by the brain’s own immune cells (microglia). The result is a dramatic reduction in amyloid plaque in the brain, as visualized on follow-up amyloid PET scans.

Who is a Candidate for DMTs?

This is the most critical question. These are not drugs for everyone with memory problems. The prescribing criteria are very specific and must be strictly followed to ensure safety and potential efficacy.

Key Eligibility Criteria:

• Correct Diagnosis: The patient must have a confirmed diagnosis of Mild Cognitive Impairment (MCI) due to Alzheimer’s disease or mild-stage Alzheimer’s disease dementia. These drugs are not approved for, and have not been shown to work in, the moderate-to-severe stages of the disease.
• Confirmed Amyloid Pathology: This is non-negotiable. The patient must have a positive amyloid PET scan or a CSF test confirming the presence of amyloid plaques. You cannot give an anti-amyloid drug to someone who doesn’t have amyloid.
• Appropriate Age and Clinical Stage: The clinical trials focused on a specific population, and treatment should be initiated in patients who match that profile.
• Safety Screening: Patients must undergo an MRI before starting treatment and regular monitoring MRIs during treatment to screen for a significant side effect known as ARIA.

The Risks: Amyloid-Related Imaging Abnormalities (ARIA)

The primary risk associated with anti-amyloid therapies is ARIA (Amyloid-Related Imaging Abnormalities). This is a radiological finding seen on MRI scans and can manifest in two ways:

• ARIA-E (Edema): Represents localized brain swelling, caused by fluid leaking from blood vessels.
• ARIA-H (Hemorrhage): Represents microhemorrhages (tiny bleeds) or, more rarely, larger areas of bleeding on the surface of the brain (siderosis).

Most cases of ARIA are asymptomatic and are only detected on routine monitoring MRIs. However, in some cases, ARIA can cause symptoms such as headache, confusion, dizziness, visual changes, and nausea. In rare instances, it can be severe and life-threatening. The risk of ARIA is higher in individuals who carry the APOE4 gene, particularly those with two copies of the gene. Therefore, genetic testing for APOE status is strongly recommended before initiating treatment to inform the risk-benefit discussion.

The Future of Treatment

The approval of lecanemab and the promising results from donanemab mark a turning point. These are the first drugs convincingly shown to change the underlying course of Alzheimer’s disease. While the clinical benefit is modest—slowing decline by about 27- 35% over 18 months in the pivotal trials—it is a crucial first step. It proves that targeting the disease’s biology can work.

Future research is focused on:

• Anti-Tau Therapies: Drugs targeting the tau tangles are in late-stage clinical trials. A combination of anti-amyloid and anti-tau therapy may be more effective.
• Earlier Intervention: Moving treatment into the preclinical (asymptomatic) stage to prevent symptoms from ever developing.
• Other Pathological Targets: Developing drugs that target inflammation, vascular factors, and metabolic dysfunction.

Conclusion: An Integrated and Hopeful Path Forward

We stand at a pivotal moment in the history of Alzheimer’s disease. The convergence of advanced biological diagnostics, such as the ATN framework, and the arrival of the first disease-modifying therapies has opened a new chapter of hope. We have moved from a position of simply managing decline to one where we can actively intervene in the disease process itself.

However, the complexity of the aging brain, with its frequent mixed pathologies, teaches us that there will be no single magic bullet. The most effective approach will be comprehensive, personalized, and integrative. This is the philosophy that guides our work at Injury Medical Clinic PA.

By combining the medical expertise of Dr. Cardenas for pharmacological management with the holistic, neuro-functional focus of integrative chiropractic and functional medicine, we can provide our patients with the most robust support system possible. Our approach addresses the disease from multiple angles: targeting the underlying pathology with DMTs, managing symptoms with carefully chosen medications, and simultaneously optimizing the body’s own health and resilience through lifestyle, nutrition, and neuro-structural care. My own clinical observations, which I often share on platforms like Chiropractic Scientist and my LinkedIn profile, consistently reinforce that patients who address musculoskeletal pain, improve their sleep, and reduce systemic inflammation experience better overall function and quality of life.

The journey with dementia is challenging, but with timely and accurate diagnosis, a multifaceted treatment plan, and a dedicated, collaborative clinical team, we can significantly improve the quality of life for those living with the disease and provide their families with the support and hope they deserve.

References

1. Ackley, S. F., Zimmerman, S. C., Brenowitz, W. D., Tchetgen, E. J. T., Gold, A. L., Manly, J. J., Mayeda, E. R., & Glymour, M. M. (2021). Effect of reductions in amyloid levels on cognitive change in randomized trials: A meta-analysis. BMJ, 372, n156.
2. Cummings, J., Zhou, Y., Lee, G., Zhong, K., & Fonseca, J. (2025). Alzheimer’s disease drug development pipeline: 2025. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 11(1), e12564.
3. Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: Few candidates, high failure rate. Alzheimer’s Research & Therapy, 6(4), 37.
4. Howard, R., McShane, R., Lindesay, J., Ritchie, C., Baldwin, A., Barber, R., Burns, A., Dening, T., Findlay, D., Holmes, C., Hughes, A., Jacoby, R., Jones, R., Jones, R., McKeith, I., Macharouthu, A., O’Brien, J., Passmore, P., Phelan, M., … & Phillips, P. (2012). Donepezil and memantine for moderate-to-severe Alzheimer’s disease. New England Journal of Medicine, 366(10), 893-903.
5. Jack, C. R., Jr., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., & Sperling, R. (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia, 14(4), 535–562.
6. Jack, C. R., Jr., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Trojanowski, J. Q., & Alzheimer’s Disease Neuroimaging Initiative. (2013). Tracking the long-term evolution of AD biomarkers. The Lancet Neurology, 12(7), 643-645.
7. Poli, M., Vilor-Tejedor, N., Valldeneu, S., Pizarro, J., Arranz, A. M., Sala-Vila, A., Minguillon, C., Fauria, K., & Zetterberg, H. (2023). Long-term brain changes in cognitively unimpaired individuals with amyloid-related imaging abnormalities. Annals of Neurology, 93(2), 297–310.
8. Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S., & Möbius, H. J. (2003). Memantine in moderate-to-severe Alzheimer’s disease. New England Journal of Medicine, 348(14), 1333-1341.
9. Robinson, J. L., Corrada, M. M., Kovacs, G. G., Último, G., Lowe, V. J., Katsumata, Y., Executive Committee of the Advancing Neuropathology and Neuroscience Research and Education (ANNRAE), & a collaboration of six prospective community-based autopsy studies. (2023). Neuropathological-clinical correlations of cognitive impairment in a community-based cohort. The Lancet Neurology, 22(7), 585–597.
10. Rogers, S. L., Doody, R. S., Mohs, R. C., & Friedhoff, L. T. (1998). Donepezil improves cognition and global function in Alzheimer disease: A 15-week, double-blind, placebo-controlled study. Archives of Internal Medicine, 158(9), 1021–1031.
11. Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., & Monane, M. (2023). Donanemab in early symptomatic Alzheimer disease: The TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA, 330(6), 512–527.
12. Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S., Gergel, I., & Memantine Study Group. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA, 291(3), 317–324.
13. van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., & Cohen, S. (2023). Lecanemab in early Alzheimer’s disease. The New England Journal of Medicine, 388(1), 9–21.

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