Integrative Therapies in Action for Cognitive Decline

Learn about cognitive decline and integrative therapies aimed at supporting cognitive health and preventing decline.

Educational Abstract: Pharmacological Management of Dementia, Diagnostic Advances, and Integrative Chiropractic Care in a Multidisciplinary Clinic

As Dr. Alexander Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST, I present an educational, evidence-based overview of modern dementia care—focusing on Alzheimer’s disease—through a comprehensive lens that integrates internal medicine, neurology, functional medicine, rehabilitation, personal injury care pathways, and chiropractic neurophysiology. I explain current diagnostic logic, from symptom-driven models to biomarker-driven frameworks (ATN: amyloid, tau, neurodegeneration), the clinical significance of co-occurring neuropathologies, and the rationale for structured pharmacologic and non-pharmacologic treatment plans. I highlight how our multidisciplinary team in El Paso, Texas—under the medical direction of Dr. Maria Guadalupe Cardenas, MD (Board Certified in Internal Medicine) (NPI #1164426749, Texas MD License #J2933)—collaborates at Injury Medical Clinic PA (Mission Plaza Injury Medical Clinic) to provide medical oversight, diagnostic alignment, and integrative chiropractic care across cognitive, autonomic, and neuromusculoskeletal domains. I summarize the latest disease-modifying therapies (DMTs), including amyloid-targeted monoclonal antibodies (aducanumab, lecanemab, donanemab), real-world risks like amyloid-related imaging abnormalities (ARIA), and how genetics (APOE4) influences safety and monitoring. I detail the state of blood-based biomarkers (phospho-tau217, GFAP, NfL), the role of PET scans and lumbar punctures, polypharmacy considerations, behavioral and neuropsychiatric symptom management, cardiovascular and perfusion principles, neuroinflammation, lifestyle factors, and rehabilitative strategies. This post is designed to guide patients, families, and clinicians through a clear journey from diagnosis to targeted interventions using modern, validated methods.

Introduction: How I Think Through Dementia in Clinical Practice

I am Dr. Alexander Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST. In my practice at Injury Medical Clinic PA (Mission Plaza Injury Medical Clinic) in El Paso, Texas, I work alongside our Medical Director and Collaborative Physician, Dr. Maria Guadalupe Cardenas, MD (Board Certified in Internal Medicine) (NPI #1164426749, Texas MD License #J2933), who has more than 40 years of experience in internal medicine. Our multidisciplinary clinic structure is a model increasingly common in integrative and injury care settings—where an MD provides medical direction and diagnostic oversight in concert with chiropractic, functional medicine, rehabilitation, and personal injury services. This powerful synergy between different medical disciplines is a philosophical commitment to treating the whole person.

When a patient presents with memory changes, executive function difficulties, or new behavioral changes, I begin with a structured pathway that prioritizes clarity and safety. My approach is informed by leading research and clinical frameworks from neurology, internal medicine, and geriatrics. I also integrate chiropractic neurophysiology and functional medicine strategies to address perfusion, autonomic imbalance, neuroinflammation, and biomechanical stressors that may compound cognitive symptoms.

This educational post summarizes:

• The modern diagnostic approach to Alzheimer’s disease and related dementias, including symptom criteria and biomarker frameworks such as ATN.
• Why co-existing neuropathologies are common and how that changes treatment logic.
• The pharmacologic approach for cognitive and neuropsychiatric symptoms, from established medications to emerging therapies.
• The role of disease-modifying therapies, including who is a candidate and how to manage them safely.
• How our team integrates chiropractic care with internal medicine oversight, functional medicine, and rehabilitation.
• Practical care strategies for patients and families, supported by contemporary evidence.

Throughout, I share the rationale behind each clinical decision—why we choose a given test, why we consider a certain medication, and how integrative chiropractic care fits into the therapeutic plan.

The Foundation of Diagnosis: A Deep and Methodical Symptom History

When a patient presents with concerns about their memory or thinking, our journey begins with the most fundamental step: taking a thorough, detailed symptom history. This is far more than a simple checklist of symptoms. It is an investigative process, a narrative we build together to understand the full picture of what the patient is experiencing. I always ask a series of probing questions to paint this picture as clearly as possible:

• “When did you first notice these changes?”
• “Can you describe for me what it feels like when you have a ‘senior moment’ or a lapse in memory?”
• “What specific situations seem to be the most challenging for you?”
• “Is there anything you’ve found that seems to make your thinking clearer or, conversely, what makes the fogginess worse?”
• “Are there any other symptoms that have appeared around the same time, even if they seem unrelated?”

It is crucial to explore not just the cognitive symptoms, such as memory loss or difficulty with problem-solving, but also the psychiatric symptoms. We know that conditions like anxiety and depression often co-occur with cognitive decline and can significantly impact a person’s quality of life. Understanding these associated symptoms is vital for a comprehensive treatment plan.

The Value of a Secondary Historian

A unique and best-practice element in evaluating cognitive decline is gathering information from a secondary historian. This is not necessarily a formal “caregiver” but rather someone who knows the patient well—such as a spouse, an adult child, or a close friend—and with whom the patient is comfortable sharing information. The flow of information is directed to me, the clinician, to enrich the history, not from me to this other person.

In my clinical experience, most patients are very open to this. We all have blind spots: habits, behaviors, or subtle changes in our daily functioning that we may not recognize in ourselves but that are apparent to those who spend a lot of time with us. This secondary perspective provides an invaluable layer of detail, helping to corroborate the patient’s report and often revealing changes in activities of daily living or social interactions that the patient might have overlooked or minimized. This collaborative approach to history-taking is where the diagnostic process truly begins.

My Diagnostic Philosophy: Moving From Symptoms Alone to Biomarkers and Structured Logic

When I evaluate cognitive decline, I consider two parallel tracks:

• Symptom-based classification: What is measurable, observable, and functionally impactful?
• Biomarker-based classification: What is the neurobiological substrate driving symptoms?

Traditionally, many clinicians diagnosed probable Alzheimer’s disease by observing the pattern and onset of cognitive symptoms: insidious onset, progressive memory impairment with poor recall of recent events despite cues, and deterioration in other domains such as language, visuospatial skills, and executive function. Advanced age is the strongest risk factor. However, our diagnostic logic has shifted to incorporate biomarkers, which reflect the presence and sequence of disease processes long before symptoms appear.

I educate patients and families that the pathophysiology begins years—often 15 to 20—before cognitive testing demonstrates impairment. During this subclinical window, amyloid and tau accumulate, transitioning from soluble forms to aggregated plaques (amyloid) and neurofibrillary tangles (tau), eventually killing neurons and leading to measurable neurodegeneration. This sequence has been elegantly detailed by researchers who have modeled biomarker dynamics over time.

The key takeaways I emphasize:

• Amyloid accumulation appears early and likely initiates a cascade that facilitates tau pathology.
• Tau pathology correlates more tightly with symptom severity and progression once clinical impairment is evident.
• Neurodegeneration—loss of brain volume and network integrity—accumulates steadily and becomes visible on imaging or measurable via emerging blood biomarkers.

This framework sets the stage for targeted testing and treatment decisions.

The Comprehensive Diagnostic Workup: Beyond the Initial Conversation

Following the detailed history, we move on to a structured, multifaceted evaluation. Each component is a piece of the puzzle, helping us narrow down the potential causes of the cognitive changes.

The Neurological Examination

A comprehensive neurological exam is a standard part of our workup. In the early stages of many neurodegenerative conditions, I may not expect to find major neurological deficits. Things like deep tendon reflexes, gait, and mobility might appear normal for quite some time, depending on the underlying pathology. However, the exam is still essential. It establishes a baseline and can sometimes reveal subtle signs that point us in a specific direction. For example, slight changes in gait or balance could suggest a vascular component to the cognitive decline or hint at other neurological conditions.

Assessing Mood and Mental Health

It is impossible to accurately assess cognition without also assessing mood. Therefore, administering scales for depression and anxiety is a critical step. However, a significant challenge is that many standard screening tools, such as the Patient Health Questionnaire-9 (PHQ-9), have not been validated for individuals living with moderate-to-advanced cognitive decline. A person who has impairments in judgment, reasoning, and memory may struggle to accurately self-report their symptoms on these questionnaires.

Despite these limitations, I find these tools helpful as a starting point. They can open up a conversation about mood and provide a preliminary indication of a potential co-occurring psychiatric condition. For patients with more significant cognitive impairment, we may consider using neuropsychiatric scales specifically designed for this population, which often rely more on observable behaviors and caregiver reports.

The Power of Neuropsychological Testing

Neuropsychological testing is an incredibly powerful and helpful tool. If available within a patient’s health system, I strongly recommend it. Neuropsychologists conduct comprehensive evaluations that go far beyond the brief cognitive screens we might administer in the clinic. They involve a battery of standardized tests that measure various cognitive domains in detail, including:

• Attention and concentration
• Executive functions (planning, organizing, problem-solving)
• Language abilities
• Visuospatial skills
• Learning and memory (both verbal and visual)

The detailed report from a neuropsychological evaluation provides an objective profile of a person’s cognitive strengths and weaknesses. This is invaluable for me as a clinician in narrowing down a diagnosis, distinguishing between different types of dementia, and establishing a robust baseline against which we can measure future changes or the effects of treatment. Fortunately, neuropsychology practices are often available in the community and provide testing for learning differences and other conditions, making them somewhat more accessible than other subspecialties.

Visualizing the Brain: The Role of Neuroimaging

In the primary care and integrative setting, our initial approach to neuroimaging typically begins with structural imaging. The preferred modality is a Magnetic Resonance Imaging (MRI) of the brain. An MRI provides a detailed look at the brain’s structure, allowing us to identify:

• Evidence of strokes (both large and small)
• Tumors or other masses
• Hydrocephalus (excess fluid in the brain)
• Patterns of atrophy (shrinkage) in specific brain regions, which can be suggestive of certain types of dementia (e.g., hippocampal atrophy in Alzheimer’s disease)

If a patient is unable to undergo an MRI (for instance, due to a pacemaker or severe claustrophobia), a Computed Tomography (CT) scan is an alternative. However, it provides less detailed soft-tissue contrast. Structural imaging is essential for ruling out “reversible” or treatable causes of cognitive symptoms and for identifying cerebrovascular disease that may be contributing to the clinical picture.

Essential Laboratory Studies

Before jumping to more specialized tests, it is critical to perform a panel of basic laboratory studies. These “Tier 1” tests, as outlined in recent guidelines, help us identify systemic medical issues that can masquerade as or exacerbate cognitive decline. If a patient hasn’t had recent lab work, this is a non-negotiable step. Our standard panel includes:

• Complete Blood Count (CBC): To check for anemia or infection.
• Comprehensive Metabolic Panel (CMP): To assess kidney function, liver function, and electrolyte balance.
• Thyroid-Stimulating Hormone (TSH): To screen for hypothyroidism, a well-known cause of cognitive slowing and “brain fog.”
• Vitamin B12: To check for deficiency, which can cause significant neurological and cognitive symptoms.
• Folate: Deficiency can also contribute to cognitive symptoms.
• Inflammatory Markers: such as C-reactive protein (CRP), to gauge the body’s overall inflammatory state.

This foundational lab work ensures we are not overlooking a treatable metabolic or nutritional deficiency that could be the primary driver of the patient’s symptoms.

The ATN Framework: Amyloid, Tau, Neurodegeneration

I use the ATN criteria to anchor our diagnostic plan:

• A: Amyloid pathology—measured via amyloid PET or CSF Aβ42/Aβ40 ratios. Blood-based amyloid assays are advancing and increasingly accurate, though not yet considered the gold standard for definitive diagnosis.
• T: Tau pathology—measured via CSF phosphorylated tau (p-tau) or tau PET. Emerging blood-based p-tau assays provide valuable information and may serve as proxies for amyloid burden and tau status.
• N: Neurodegeneration—measured via structural MRI (preferably) or CT, and increasingly via blood markers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). These tests reflect neuronal injury and glial activation.

In our clinic, under Dr. Cardenas’s medical direction, we pursue ATN testing when symptoms warrant it. We do not recommend biomarker testing in completely asymptomatic individuals because age-related changes may elevate markers without clear clinical significance.

Why ATN matters:

• It enables timely and accurate identification of Alzheimer’s disease processes.
• It guides eligibility and timing for disease-modifying treatments.
• It informs prognostic counseling, clarifying why certain symptoms are present and what might evolve.
• It supports personalized treatment planning, including pharmacology, rehabilitation, and lifestyle recommendations.

Advanced and Specialized Testing: A Look into the Future

Once we have completed the foundational workup, we can discuss with the patient pursuing more specialized testing. This decision is highly individualized and depends on the clinical scenario, the patient’s wishes, and their candidacy for emerging treatments. These advanced tests include:

• Plasma-Based Biomarkers: These are exciting new blood tests that can detect the protein pathologies of Alzheimer’s disease (amyloid and tau) with increasing accuracy. You will encounter markers like p-tau217, GFAP, NfL, and Aβ42/Aβ40 ratios. These offer a less invasive way to gain biological evidence of the disease, improve diagnostic confidence, and guide referrals.
• Cerebrospinal Fluid (CSF) Analysis: This involves a lumbar puncture (spinal tap) to directly measure the levels of amyloid and tau proteins in the fluid that bathes the brain and spinal cord. It remains a gold standard for biological confirmation of Alzheimer’s pathology.
• Amyloid PET Scans: This is an advanced imaging technique where a radioactive tracer that binds to amyloid plaques is injected, allowing us to visualize the amyloid burden in the living brain.
• Genetic Testing: Specifically, testing for the Apolipoprotein E (APOE) gene, particularly the e4 allele, which is a significant genetic risk factor for late-onset Alzheimer’s disease.

It is crucial to emphasize that pursuing this level of testing is a significant decision. It is often done in the context of considering disease-modifying treatments, such as the newer amyloid-targeted therapies, as eligibility for these treatments currently requires confirmation of amyloid pathology via PET or CSF.

Understanding Co-Occurring Neuropathologies: Why Brains Rarely Have One Pathology

One of the most important realities I share with patients is that multiple neuropathologies often co-exist. Large-cohort autopsy data have shown that individuals frequently exhibit combinations of amyloid plaques, tau tangles, micro- and macroinfarcts (vascular pathology), Lewy bodies (alpha-synuclein pathology), and TDP-43 pathology (commonly associated with later-onset limbic-predominant age-related TDP-43 encephalopathy, often overlapping with frontotemporal patterns).

Clinical implications:

• It is common to see Alzheimer’s biomarkers alongside Lewy body pathology or vascular changes.
• Mixed pathology explains heterogeneous symptom profiles—for example, Alzheimer’s biomarkers with prominent visuospatial or executive dysfunction, parkinsonian features, or fluctuating attention.
• Treatment often requires multimodal strategies rather than relying on a single pharmacologic agent.
• Patients may benefit from precision counseling that acknowledges that overlapping pathologies require nuanced monitoring and layered interventions.

This understanding also reframes expectations about disease-modifying therapies. If multiple pathological processes are present, addressing only one may yield modest benefits unless accompanied by strategies to mitigate vascular risk factors, autonomic dysfunction, neuroinflammation, sleep disturbances, and physical deconditioning.

The DetectAD Guidelines: A New Framework for Diagnosis

A new set of clinical practice guidelines has recently revolutionized the field of dementia diagnosis. These guidelines, supported by the Alzheimer’s Association and published in 2025 in the journal Alzheimer’s & Dementia, are called DetectAD. They were developed by a panel of experts following a rigorous literature review and provide a clear, structured framework for clinicians. Importantly, the guidelines offer distinct pathways for primary care clinicians and dementia subspecialists, acknowledging that most initial evaluations occur in primary care settings.

Core Elements of the DetectAD Evaluation

The DetectAD framework is built around several core elements, with communication serving as the bookends of the entire process.

1. Establishing Expectations and Goals: The very first step is a conversation about the diagnostic process itself. What can the patient expect? What are their goals? Do they even want a specific diagnosis? We must respect a patient’s autonomy; just because we can perform a test does not mean the patient wants it. This initial conversation also establishes who should be involved. The guidelines strongly recommend that a trusted family member or friend participate in this shared journey.
2. Comprehensive Assessment: This mirrors the multifaceted workup we have already discussed:

• • History Taking: Covering cognitive, functional (activities of daily living), neuropsychiatric, and sensory-motor symptoms.
  • Medical, Social, and Family History: Identifying risk factors is key. We know that conditions like diabetes, hypertension, chronic kidney disease, sleep apnea, and substance use disorders are significant risk factors for both neurodegenerative and cerebrovascular diseases. The concept of Alzheimer’s as “type 3 diabetes,” while perhaps an oversimplification, highlights the profound connection between metabolic health and brain health.
  • Clinical Examination: Including a formal mental status exam using a validated tool. While the Medicare Annual Wellness Visit allows for a simple query about memory, the guidelines advocate for at least a Mini-Cog or a similar brief, validated instrument.

• Synthesizing and Staging: After gathering all the information, the clinician’s job is to synthesize it to arrive at a diagnosis. This involves:

• • Categorizing the Syndrome: Is the person cognitively unimpaired? Do they have Subjective Cognitive Decline (SCD), where they feel a change, but we cannot yet measure it on tests? Do they have Mild Cognitive Impairment (MCI), where there are measurable deficits, but their daily functioning remains independent? Or do they have dementia, where the cognitive impairment is severe enough to interfere with independence in daily life?
  • Staging Dementia: If dementia is diagnosed, it should be staged as mild, moderate, or severe using tools like the Clinical Dementia Rating (CDR).
  • Determining Etiology: The final step is to determine the most likely underlying cause (e.g., “dementia most likely due to Alzheimer’s disease”). This entire process informs our ICD-10 coding, ensuring accurate documentation.

• Communicating Findings and Shared Care Planning: The final core element brings us back to communication. The diagnosis and its implications must be communicated clearly and compassionately, not just to the patient but also to their care partner. The subsequent care plan is not something dictated by the clinician; it is developed collaboratively, reflecting the shared goals and values of the patient and their family.

A Phased Approach to Evaluation

The DetectAD guidelines emphasize that this comprehensive evaluation is not meant to be completed in a single, rushed 15-minute appointment. When a concern for cognitive impairment arises, I often find it most effective to schedule a dedicated, longer follow-up visit. This allows us to give the concern the time and attention it deserves. Studies have shown that patients who voice subjective cognitive concerns to their primary care providers and receive no further evaluation often feel frustrated and dismissed. A dedicated visit validates their concerns and initiates a thoughtful, structured process. This also means we do not just “jump right to the referral.” We do the foundational work first.

The Shifting Paradigm: Is Alzheimer’s a Single Disease?

We are living in an era where our very understanding of Alzheimer’s is being challenged. We are moving away from the idea of it being one single entity and toward a more nuanced view of it as a spectrum of Alzheimer’s disease disorders. The biological underpinnings are complex and heterogeneous. A person might have:

• An amyloidopathy (a primary problem with amyloid protein accumulation).
• A tauopathy (a primary problem with tau protein tangles).
• A mixed picture involving both, along with other pathological proteins.
• Significant contributions from inflammation, vascular damage, or exposure to toxins.

This complexity leads to a critical new conversation in our field: the distinction between preclinical Alzheimer’s disease (the presence of positive biomarkers like amyloid plaques but no symptoms) and symptomatic Alzheimer’s disease. Currently, our treatments and clinical focus are almost exclusively on the symptomatic stage. We do not yet have an evidence-based consensus on what to do for an individual who has the brain pathology of Alzheimer’s but is completely asymptomatic.

From a patient’s perspective, this can raise the question: “Does it really matter if it’s Alzheimer’s?” The answer is, “It depends.” For now, the symptom burden remains the primary guide for our treatment plan. However, as new therapies emerge that target specific pathologies, knowing the underlying biological cause will become increasingly critical for selecting the right treatment for the right patient. While I always respect a patient who says, “I’m not interested in knowing the label,” I also explain that knowing the likely cause can be immensely helpful for me, as their clinician, in crafting the most effective and personalized management strategy.

Understanding Clinical Trial Outcomes in Alzheimer’s Research

When we discuss the effectiveness of Alzheimer’s medications, you’ll often hear references to specific assessment tools used in clinical trials. You need to understand what these tools measure, as it helps put the “clinical meaningfulness” of a drug’s effect into perspective.

Key Assessment Tools

• Clinical Dementia Rating (CDR): I am a big fan of the CDR. It evaluates a person across six key domains: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. The “Sum of Boxes” (CDR-SB) score is a global measure derived from these categories, providing a comprehensive snapshot of a person’s functional and cognitive status.
• Mini-Mental State Examination (MMSE): This is a well-known 30-item questionnaire that assesses various cognitive functions, such as orientation, recall, attention, and language. A lower score indicates greater cognitive impairment.
• Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): Another widely used tool in clinical trials, the ADAS-Cog is a more detailed assessment of cognitive dysfunction, particularly memory and language. Unlike the MMSE, a higher score on the ADAS-Cog signifies greater impairment.

Understanding these tools is the first step in interpreting the data on the medications we’re about to discuss.

Pharmacologic Management of Cognitive Symptoms: Evidence and Rationale

Alzheimer’s disease and related disorders commonly utilize two established classes of cognitive-symptom medications: cholinesterase inhibitors and NMDA receptor antagonists.

Acetylcholinesterase Inhibitors: The First Line of Symptomatic Treatment

For the last 25 years, the cornerstone of symptomatic treatment for mild to moderate Alzheimer’s disease has been the class of drugs known as acetylcholinesterase inhibitors. The most commonly used agents are donepezil (brand name Aricept), rivastigmine (brand name Exelon), and galantamine.

How Do They Work?

The primary mechanism of action of these medications is to prevent the breakdown of acetylcholine in the brain. Acetylcholine is a crucial neurotransmitter involved in memory, learning, and most notably, attention. The logic is straightforward: you cannot remember something if you did not pay attention to it in the first place. In Alzheimer’s disease, the brain cells that produce acetylcholine are progressively destroyed. By inhibiting the enzyme (acetylcholinesterase) that breaks down acetylcholine, these drugs increase its availability in the synaptic cleft, helping to bolster attentional networks and overall communication between brain cells. This is also why we are so careful to avoid anticholinergic medications (like certain allergy medicines, overactive bladder drugs, or sleep aids), as they have the opposite effect and can worsen cognitive function.

Reviewing the Clinical Evidence

Let’s travel back to the late 1990s and look at one of the pivotal Phase III randomized controlled trials for donepezil (Aricept). Published in 1998, this study enrolled about 450 people and followed them for six months.

The results showed a modest but statistically significant benefit. On average, patients on the active drug experienced a slight improvement or, more commonly, a slower rate of decline on cognitive measures compared to the placebo group. For example, the placebo group experienced an average decline of one point on the 30-point MMSE scale, while the donepezil group showed an average increase of 0.4 points. It is crucial to frame these expectations correctly with patients and families. These drugs are not a cure. They do not stop or reverse the underlying disease process. The goal of symptomatic treatment is to help maintain function and temporarily stabilize symptoms, potentially “turning back the clock” on the disease by about 6 to 12 months.

Adverse Effects and Monitoring

It’s easy to forget that when these drugs were first studied, the clinical trials had very strict inclusion and exclusion criteria. This was due to known adverse effects.

• Gastrointestinal Effects: A majority of patients starting donepezil will experience nausea and diarrhea to some degree. This is why we always start at a low dose (typically 5 mg) and titrate up slowly. These side effects can be significant enough to cause people to stop the medication. This is also a primary reason why some patients are switched to the rivastigmine patch, which delivers the medication transdermally and provides more stable drug levels.
• Cardiovascular Effects: A less common but more serious set of adverse effects involves electrophysiologic changes in the heart. About a quarter to a third of patients may experience bradyarrhythmias (abnormally slow heart rhythms) and syncope (fainting). The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults lists a history of syncope as a strong reason to discontinue these drugs. I have certainly encountered patients who were on a path toward getting a pacemaker for bradycardia when the real culprit was their donepezil.

Our team, under Dr. Cardenas’s medical direction, monitors heart rate, blood pressure, GI tolerance, and falls, adjusting dosing if patients develop these issues.

NMDA Receptor Antagonists: A Different Approach

The other major class of symptomatic medication is the N-methyl-D-aspartate (NMDA) receptor antagonist. The only drug in this class is memantine (brand name Namenda). It is typically used for moderate to severe Alzheimer’s disease.

How Does It Work?

Memantine works on the glutamate system. Glutamate is the most abundant excitatory neurotransmitter in the brain. In Alzheimer’s disease, it’s believed that damaged neurons leak excessive amounts of glutamate, leading to chronic overstimulation of NMDA receptors. This state, called excitotoxicity, allows a constant influx of calcium into the neuron, ultimately causing cell damage and death.

Memantine gently blocks these receptors, but only when they are being overstimulated. It doesn’t interfere with the normal signaling required for learning and memory. By blocking the “excess noise” of glutamate, memantine is thought to protect neurons from further damage.

Clinical Evidence and Side Effects

The side effects of memantine are generally less common than with acetylcholinesterase inhibitors, but some patients experience agitation or somnolence (drowsiness). A key study from the early 2000s showed that, similar to donepezil, patients on memantine maintained their cognitive scores better than the placebo group. The drug was very well-tolerated. However, memantine truly seems to shine in the functional domain, especially when combined with a cholinesterase inhibitor.

The Power of Combination Therapy

The gold standard for symptomatic treatment in moderate to severe Alzheimer’s has become the combination of an acetylcholinesterase inhibitor and an NMDA receptor antagonist.

A pivotal 2012 study published in JAMA Neurology examined this synergy by dividing patients into four groups: placebo, donepezil only, memantine only, and combination therapy.

• Cognitive Decline: A clear pattern emerged. The placebo group showed the greatest decline, the single-drug groups showed less decline, and the combination therapy group had the least amount of cognitive decline of all.
• Activities of Daily Living (ADLs): The most dramatic separation between the groups was seen in ADLs. The data showed that patients on combination therapy remained more independent and autonomous for longer. This translates directly to a better quality of life and reduced caregiver burden. This is a profoundly meaningful outcome for families.

The Real-World Implications of Symptomatic Treatments

• Modest Benefits: The improvements are not dramatic. We are promising patients that these medications may help them decline more slowly.
• High Variability: Not every patient will respond.
• Low Threshold for Discontinuation: As a clinician, I have a very low threshold for stopping these medications if a patient cannot tolerate them. If a patient on donepezil has a syncopal episode (fainting), the risk of injury from a fall far outweighs the modest cognitive benefit. The medication has to go.

Managing Neuropsychiatric Symptoms: The Hidden Crisis

I want to shift our focus to a critically important area: neuropsychiatric symptoms (NPS), also known as behavioral and psychological symptoms of dementia (BPSD). While cognitive decline is the hallmark of Alzheimer’s, it is often the NPS that cause the most distress for both patients and their families and are most likely to lead to institutional placement.

Assessing Neuropsychiatric Symptoms

The first step is to actively screen for these symptoms using validated tools like the Neuropsychiatric Inventory (NPI) or the Revised Memory and Behavior Problems Checklist (RMBPC). A crucial point about these tools is that they are validated for caregiver or care partner report. Patients may lack the insight to accurately report these symptoms, underscoring the absolute necessity of engaging a secondary historian.

Common Categories of Neuropsychiatric Symptoms

• Hyperactivity/Agitation: Agitation, pacing, rummaging, irritability, and disinhibition (saying or doing socially inappropriate things).
• Mood Symptoms: Depression & Anxiety are extremely common.
• Apathy: A profound lack of interest, motivation, or emotional response.
• Psychosis: Hallucinations (seeing or hearing things that are not there) and delusions (fixed, false beliefs, such as believing someone is stealing from them).
• Sleep & Appetite Disturbances: Nighttime behaviors and changes in appetite.

The “DICE” Approach: A Framework for Management

Before ever reaching for a prescription pad, we must investigate the root cause of the behavior. A helpful framework for this is the DICE approach: Describe, Investigate, Create, Evaluate.

1. Describe: Get a detailed description of the behavior from the caregiver.
2. Investigate: Rule out underlying physical causes. This is where our integrative model shines. We look for:

• • Physical Causes: Pain, infection (especially UTIs), constipation, dehydration, fatigue.
  • Underlying Psychiatric Conditions: Pre-existing depression or anxiety.
  • Environmental Factors: An environment that is too stimulating or under-stimulating.
  • Sensory Changes: Misinterpreting sights or sounds due to uncorrected vision or hearing loss.

• Create: Develop a non-pharmacological management plan first. This may involve simplifying the environment, establishing a predictable routine, using calming music, or engaging the person in a simple, meaningful activity.
• Evaluate: Monitor the plan’s effectiveness and adjust as needed.

A Cautious Approach to Pharmacological Intervention

If non-pharmacological strategies are insufficient, we may consider medication.

• Depression/anxiety/agitation: SSRIs (e.g., sertraline, citalopram) are often a good first choice, with attention to side effects.
• Agitation/irritability: After evaluating for pain, infection, or other triggers, short-term pharmacologic options may be considered. We avoid benzodiazepines where possible due to cognitive and fall risks.
• Psychosis: Antipsychotics should be reserved for true psychosis that is distressing or dangerous. I see far too much use of antipsychotics to help a patient sleep at night. This is an inappropriate use of this class of drugs, given their significant risks in older adults, including an increased risk of stroke and death (the basis for their “black box” warning).

Our internal medicine oversight by Dr. Cardenas is essential for managing comorbidities and drug interactions, especially when polypharmacy can produce cascading adverse effects.

The Power of Pharmacogenetic Testing

This brings me to a tool that has been a game-changer in my practice: pharmacogenetic testing. This simple cheek swab analyzes a person’s genes to predict how they will metabolize and respond to various medications, including antidepressants and antipsychotics.

In a population with a limited life expectancy, we do not have the luxury of the traditional “trial-and-error” method, which can waste three to six months. Pharmacogenetic testing provides a roadmap, helping us get to the right treatment faster and more safely. It has been surprisingly easy to implement in our practice, with good insurance coverage, and it provides immeasurable value.

Disease-Modifying Therapies (DMTs): The Evolving Landscape

For decades, our treatments have been purely symptomatic. But the landscape is rapidly changing. We are now entering an era of disease-modifying therapies that target the underlying biology of Alzheimer’s disease.

Amyloid-Targeted Therapies: What We Know About Aducanumab, Lecanemab, and Donanemab

I cover three notable monoclonal antibodies that target and remove amyloid from the brain:

• Aducanumab: Achieved accelerated approval due to robust amyloid reduction but lacked consistent cognitive benefits across trials and carried significant ARIA risk. The evidence showed one positive and one negative Phase 3 outcome, raising questions about efficacy.
• Lecanemab: Demonstrated statistically significant slowing of cognitive decline in early Alzheimer’s, with a defined safety profile and ARIA risk stratified by APOE4 status.
• Donanemab: Showed slowing of progression with trial-based staging and adaptive dosing; also associated with ARIA risk modulated by APOE4 genetics.

What ARIA Is and Why Genetics Matters

The major safety concern with these therapies is ARIA, short for amyloid-related imaging abnormalities, which comes in two flavors detected on MRI:

• ARIA-E: vasogenic edema or sulcal effusions.
• ARIA-H: microhemorrhages or superficial siderosis.

Risk is substantially higher in APOE ε4 carriers, especially those who are ε4/ε4. In trial data, ε4/ε4 carriers experienced ARIA at rates roughly double or higher than non-carriers. In our clinic, we incorporate APOE genotyping into the pre-eligibility workup. It refines risk estimates and anchors informed consent. Some systems may exclude ε4/ε4 from treatment due to elevated risk.

Who Is a Candidate and When

The evolution of these FDA-approved anti-amyloid therapies has created a new pathway in care. We use a checklist under medical direction to determine candidacy:

• Clinical stage: Greatest potential benefit is in early symptomatic phases (MCI due to Alzheimer’s or mild Alzheimer’s dementia).
• Biomarker confirmation: Candidacy requires amyloid positivity via PET or CSF; emerging blood biomarkers may play a supportive role but are not yet sufficient for eligibility.
• MRI baseline: Assess for structural vulnerabilities, such as extensive microhemorrhages, which may increase risk.
• Medical comorbidities: Cardiovascular stability and anticoagulation considerations are key.
• Patient goals and logistics: Expectations must be realistic; DMTs modify the disease trajectory rather than cure pathology. Patients and families must be willing to commit to regular infusions and monitoring.

With Dr. Cardenas leading medical direction, our team ensures that candidates receive baseline MRI, neurological evaluation, and clear follow-up plans, coordinating with specialty centers as needed.

Our Integrative Model: How Chiropractic Care Fits With Medical Oversight, Functional Medicine, and Rehabilitation

While chiropractic is not a direct “treatment” for Alzheimer’s disease, its principles and practices play a powerful supportive role. At Injury Medical Clinic PA, we build comprehensive plans that do not compete with DMTs but rather optimize patient resiliency, reduce falls, and maintain independence.

The Role of Integrative Chiropractic Care in Supporting Cognitive Health

My approach as a Doctor of Chiropractic is rooted in several key areas:

• Optimizing Nervous System Function: Through gentle, specific chiropractic adjustments, my goal is to restore proper motion and alignment to the spinal joints. This can improve proprioception (the body’s sense of position), reduce chronic pain signals that act as a physiological stressor, and help balance the autonomic nervous system (ANS), shifting it away from a dominant “fight-or-flight” state that is detrimental to brain health.
• Enhancing Cerebral Blood Flow and CSF Dynamics: Proper movement of the cervical spine (the neck) is thought to facilitate optimal blood flow to the brain. Furthermore, the gentle, rhythmic motion induced by spinal adjustments may help promote the circulation of cerebrospinal fluid (CSF), which is critical to the brain’s waste-cleansing system (the glymphatic system).
• Addressing Musculoskeletal Comorbidities: Patients with cognitive decline are at a high risk for falls. By improving gait, balance, and managing pain through non-pharmacological means, we can directly reduce fall risk, which is a major cause of morbidity and loss of independence.
• Autonomic regulation: Gentle spine and rib cage mobilization, diaphragmatic mechanics training, and postural interventions can normalize autonomic tone, supporting heart rate variability (HRV), sleep quality, and sympathetic-parasympathetic balance.
• Perfusion optimization: Cervicothoracic mobility and scapulothoracic mechanics influence respiratory efficiency, which contributes indirectly to brain clearance pathways.
• Pain modulation: Chronic pain amplifies stress hormones, disrupts sleep, and worsens cognition. By addressing spinal dysfunctions, we may reduce nociceptive load and improve daily function.
• Gait and fall risk: Targeted balance and gait work reduces fall risk and helps preserve independence.

A Functional Medicine and Lifestyle-Based Approach

My practice is deeply integrated with the principles of functional medicine, which seeks to understand the root causes of dysfunction. In collaboration with Dr. Cardenas, we guide our patients on key lifestyle modifications that form the bedrock of brain health:

• Nutrition: Guidance on an anti-inflammatory, nutrient-dense diet.
• Exercise: Personalized programs that include aerobic activity, strength training, and balance work.
• Sleep: Emphasis on sleep hygiene and treatment of underlying sleep disorders like sleep apnea.
• Stress Management: Teaching stress-reduction techniques and using chiropractic adjustments to help modulate the body’s physiological stress response.

This collaborative model ensures that every patient receives a holistic assessment and a care plan that leverages the strengths of multiple disciplines. For our patients with Alzheimer’s disease, this means we are not just prescribing medication; we are building a supportive framework to enhance cognitive resilience, manage behavioral symptoms, and maintain physical function.

Clinical Observations From My Practice

Drawing from cases shared through resources like Sciatica Clinic and professional channels, I consistently observe:

• Patients with chronic neck and thoracic dysfunction who receive gentle, tailored chiropractic care often experience improved sleep, reduced headaches, and steadier mood—factors that indirectly support cognition.
• Breathing mechanics training reduces sympathetic drive, stabilizes HRV, and improves energy levels, which correlates with better daily functioning.
• Coordinated internal medicine oversight from Dr. Cardenas reduces adverse medication events, enabling patients to benefit from cognitive enhancers and other therapies with fewer complications.

These patterns, which you can explore further through my work at Sciatica Clinic and my professional profile, reinforce that integrative care is not ancillary—it is central to maintaining function and quality of life.

Conclusion: A Modern, Integrative Pathway for Dementia Care

The journey through cognitive decline is complex and deeply personal. As clinicians, our role has evolved from simply managing symptoms to becoming navigators, investigators, and care partners. The latest research and guidelines provide us with a methodical framework for diagnosis, emphasizing thoroughness and shared decision-making. Our therapeutic landscape is expanding, offering not only established symptomatic treatments but also the promise of disease-modifying therapies that target the underlying biology of Alzheimer’s disease.

At Injury Medical Clinic, we believe the most effective approach is integrative. The collaboration between the medical oversight provided by Dr. Cardenas and the holistic, function-focused approach of chiropractic and functional medicine allows us to care for the whole person. By optimizing nervous system function, improving musculoskeletal health, reducing pain, and empowering patients with lifestyle strategies, we aim to enhance their quality of life, maintain their independence for as long as possible, and support them and their families on every step of this challenging journey. We hope that this knowledge empowers you and underscores our commitment to providing comprehensive, evidence-based, and compassionate care.

References

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Disclaimer: This post is for educational purposes only and does not constitute medical advice. Please consult with a qualified healthcare professional for any health concerns.

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