Tag: El Paso

Integrative Therapies You Need for Cognitive Decline

Uncover effective integrative therapies for cognitive decline to help maintain cognitive function and improve quality of life.

Modern Dementia Care, Biomarkers, and Integrative Therapies

Hello, I’m Dr. Alex Jimenez. Welcome to our educational post on the complex landscape of dementia, with a special focus on Alzheimer’s disease. As a clinician with a diverse background spanning chiropractic (DC), advanced practice nursing (APRN, FNP-BC), and functional medicine (CFMP, IFMCP, ATN, CCST), I am passionate about integrating different fields of knowledge to provide comprehensive, patient-centered care.
At our practice, Injury Medical Clinic PA, we believe in a multidisciplinary approach to health. I work in close collaboration with Dr. Maria Guadalupe Cardenas, MD, our Medical Director. Dr. Cardenas is a highly respected, board-certified Internist with over four decades of experience (NPI #1164426749, Texas MD License #J2933). This integrative model, in which a chiropractor and a medical doctor work side by side, allows us to blend the best of medical oversight, chiropractic care, functional medicine, rehabilitation, and personal injury management. Dr. Cardenas’s profound expertise in internal medicine provides the essential medical direction that underpins our holistic treatment strategies, ensuring our patients receive safe, effective, and well-rounded care. This collaborative environment is the foundation of our philosophy: treating the whole person, not just a set of symptoms.
Today, we will embark on an in-depth journey into the world of dementia. We will explore the latest findings from leading researchers, dissect the physiological underpinnings of these conditions, and discuss how an integrative and functional medicine perspective, including chiropractic care, can play a vital role in managing this complex health challenge.

Abstract

This educational post provides a comprehensive exploration of the pharmacological and integrative management of dementia, with a primary focus on Alzheimer’s disease. From the perspective of Dr. Alex Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST, it synthesizes current, evidence-based research into an easy-to-understand narrative. We begin by detailing the evolution of diagnostic methods for Alzheimer’s, moving from purely clinical symptom-based assessments to the modern ATN (Amyloid, Tau, Neurodegeneration) biomarker framework. This section elaborates on the roles of beta-amyloid and tau proteins, the 15-20-year preclinical phase, and advanced diagnostic tools such as PET scans, CSF analysis, and emerging blood tests. A key focus is on the reality of mixed pathologies in the aging brain, challenging the notion of a single-cause dementia and highlighting why a multifaceted treatment approach is essential.
The discussion then shifts to management strategies, covering both symptomatic treatments for cognitive and neuropsychiatric symptoms and the latest disease-modifying therapies, including amyloid-targeting monoclonal antibodies like lecanemab and donanemab. We will explore clinical trial outcome measures (MMSE, CDR-SB, ADAS-Cog), the crucial role of APOE genotyping in risk stratification for ARIA (Amyloid-Related Imaging Abnormalities), and the real-world logistics of infusion therapies and safety monitoring. I explain why we still use symptomatic treatments like acetylcholinesterase inhibitors—how they work, what benefits and risks we expect, and when we modify or discontinue them based on physiologic effects.
Finally, the post integrates these concepts within the framework of our multidisciplinary clinic, Injury Medical Clinic PA in El Paso, Texas. I explain how integrative chiropractic care, under the medical direction of our internist, Dr. Maria Guadalupe Cardenas, MD, complements functional medicine, rehabilitation, and conventional treatments to support brain health, manage systemic inflammation, and improve overall quality of life for individuals and their families navigating this journey. This post offers a comprehensive, step-by-step pathway to modern cognitive care that is human-centered and scientifically rigorous.

The Evolving Landscape of Dementia Diagnosis: Beyond Symptoms

For many years, our understanding and diagnosis of Alzheimer’s disease were almost entirely based on observing a person’s clinical symptoms—what we could see and measure in their behavior and cognitive function. This is what I refer to as the DX-before-TX principle: a precise diagnosis must precede any effective treatment. This traditional approach relied heavily on identifying a specific pattern of decline.

The Classic Clinical Diagnosis

The classic diagnostic criteria for “probable” Alzheimer’s disease focused on a set of observable changes:

• Measurable Cognitive Impairments: The core of the diagnosis was a demonstrable decline in key cognitive domains. This wasn’t just about feeling a bit forgetful; it involved objectively measured impairments in:
  • Memory: Specifically, a profound difficulty in recalling very recent events. A classic sign is the inability to remember something even with hints or prompts, indicating a problem with encoding new memories rather than just retrieving them.
  • Executive Function: This refers to the high-level mental processes that allow us to plan, organize, initiate tasks, and regulate our behavior. A decline here might manifest as difficulty managing finances, planning a multi-step recipe, or making sound judgments.
  • Language: Difficulties with word-finding (anomia), following conversations, or expressing complex thoughts.
  • Visuospatial Abilities: Problems with navigating familiar places, judging distances, or recognizing faces and objects.
  • Behavior and Personality: Changes such as apathy, social withdrawal, agitation, or uncharacteristic irritability.
• Supporting Features for Diagnosis: To support a diagnosis of probable Alzheimer’s, we would also look for other key features:
  • Insidious Onset: The changes are gradual. Families often struggle to pinpoint exactly when things started to change, describing it as a slow, creeping decline over months or years.
  • Leading Risk Factor: Advanced age remains the single greatest risk factor for developing Alzheimer’s disease.
  • The Brain Perfusion Threshold: Some researchers have explored the idea of a “cognitive reserve” or a brain perfusion threshold. The theory suggests that the underlying pathology may be present for a long time. Still, symptoms only become apparent when brain function (e.g., blood flow or neuronal activity) drops below a critical level required for normal daily functioning.

This clinical method has been our primary tool for decades. However, thanks to incredible advances in neuroscience and imaging technology, we now understand that these observable symptoms are just the tip of the iceberg, representing the final stage of a disease process that begins many years, even decades, earlier.

Unveiling the Silent Prelude: The Biomarker Revolution

The real game-changer in understanding Alzheimer’s has been the discovery and validation of biomarkers—biological signs that signal the presence of disease pathology long before cognitive symptoms become apparent. This research, much of it pioneered by brilliant minds like Dr. Clifford Jack, has completely reshaped our view of the disease timeline.

The Jack Curves: A New Timeline for Alzheimer’s

Dr. Jack’s work, often visualized in a set of graphs known as the “Jack curves,” illustrates a crucial concept: the pathological changes of Alzheimer’s disease follow a predictable sequence and begin 15 to 20 years before the first noticeable memory problems arise. This extended preclinical phase is a silent period where the brain is undergoing significant damage without producing outward symptoms.
Imagine a timeline stretching over two decades. Here is the sequence of events we now believe occurs, based on extensive research:

1. The Rise of Beta-Amyloid: The first pathological event is the accumulation of a protein called beta-amyloid. In a healthy brain, amyloid fragments are cleared away. In Alzheimer’s, they begin to clump together. Initially, they are soluble, but over time they aggregate into dense, insoluble structures known as amyloid plaques. These plaques form between neurons, disrupting communication and triggering an inflammatory response. This process starts silently, deep within the brain, nearly two decades before a person might misplace their keys and worry about their memory.
2. The Tau Cascade: The accumulation of amyloid is thought to trigger the next phase: the dysfunction of another protein called tau. Tau’s normal job is to stabilize microtubules, which are like the internal scaffolding or railway tracks inside neurons, transporting nutrients and other essential molecules. In Alzheimer’s disease, tau becomes hyperphosphorylated (it gets extra phosphate groups attached to it), causing it to detach from the microtubules and clump together inside the neurons, forming what we call neurofibrillary tangles (NFTs).
3. The Death of Neurons: Both amyloid plaques and tau tangles are toxic to brain cells. The plaques disrupt cell-to-cell signaling and provoke inflammation, while the tangles choke the neurons from the inside, leading to their death. As more and more neurons die, brain structures begin to shrink (atrophy), particularly in areas crucial for memory, like the hippocampus.
4. The Emergence of Symptoms: For years, the brain can compensate for this gradual loss of cells, a concept known as cognitive reserve. However, once a critical mass of neurons has been destroyed, the brain can no longer compensate. This is the tipping point when subtle cognitive changes first appear.
5. Clinical Diagnosis: By the time a person meets the criteria for Mild Cognitive Impairment (MCI) or dementia, they have already experienced a decade or more of progressive, underlying brain pathology.

This understanding is profound because it means we are no longer just diagnosing the disease’s end stage. We can now identify the disease process itself, opening a critical window for potential intervention long before widespread, irreversible damage occurs.

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

Building on this biomarker timeline, the scientific community has moved towards a more biological definition of Alzheimer’s disease, known as the ATN criteria. This framework, also heavily influenced by Dr. Jack’s work, classifies the disease based on the presence or absence of its core pathologies rather than solely on clinical symptoms.
The ATN framework stands for:

• A: Amyloid – Is there evidence of amyloid plaque pathology?
• T: Tau – Is there evidence of tau tangle pathology?
• N: Neurodegeneration – Is there evidence of neuronal injury or death?

This system allows for a much more precise diagnosis. A person could have amyloid pathology (A+) but not yet show signs of tau or neurodegeneration (T-, N-). This would be considered the earliest, preclinical stage of Alzheimer’s. Someone with MCI might be A+T+N+, indicating the full spectrum of pathology is present and causing symptoms.

How We Measure ATN: The Diagnostic Toolkit

Initially, this research was based on post-mortem autopsy studies. But today, we have sophisticated tools that allow us to detect these biomarkers in living individuals.

• Measuring Amyloid (A):
  • Cerebrospinal Fluid (CSF) Analysis: A sample of CSF is obtained via a lumbar puncture (spinal tap). In Alzheimer’s disease, levels of the amyloid-beta 42 protein are low in the CSF. This may seem counterintuitive, but it’s because the protein is sticking together in the brain to form plaques, so less of it is floating freely in the CSF for measurement.
  • Amyloid PET (Positron Emission Tomography) Scans: This advanced imaging technique involves injecting a radiotracer that binds to amyloid plaques in the brain. The PET scanner then detects the tracer, creating a map that “lights up” the areas of amyloid accumulation. These scans are FDA-approved and covered by Medicare in specific clinical situations.
  • Blood-Based Biomarkers: This is the most exciting and rapidly advancing frontier. We now have blood tests that can measure the ratio of amyloid-beta 42 to amyloid-beta 40 with remarkable accuracy. While not yet considered the gold standard for a definitive diagnosis, these tests are powerful screening tools. They are less invasive and less expensive than PET or CSF analysis and can help identify individuals who may need further, more definitive testing.
• Measuring Tau (T):
  • CSF Analysis: We can measure phosphorylated tau (p-tau) levels in the CSF. High levels of p-tau are a strong indicator of tau tangle pathology in the brain.
  • Tau PET Scans: Similar to amyloid PET, there are now specific tracers that bind to tau tangles, allowing us to visualize their location and density in the brain. This is particularly useful for staging the disease, as the spread of tau correlates closely with the progression of cognitive symptoms.
  • Blood-Based Biomarkers: Blood tests measuring specific forms of p-tau (like p-tau181 or p-tau217) have shown incredible promise. These tests are highly accurate in detecting Alzheimer’s pathology and can even distinguish it from other forms of dementia. They are rapidly moving from research labs into clinical practice.
• Measuring Neurodegeneration (N):
  • Structural MRI (Magnetic Resonance Imaging): An MRI can reveal brain atrophy, particularly the shrinkage of the hippocampus and other memory-related structures. While atrophy is a non-specific marker (it can occur for other reasons with aging), a pattern of atrophy that is more severe than expected for a person’s age can be a strong supportive sign of neurodegeneration.
  • FDG-PET Scans: These scans measure glucose metabolism in the brain. Areas with reduced metabolism indicate regions where neurons are either dead or dysfunctional. A classic Alzheimer’s pattern shows reduced metabolism in the temporal and parietal lobes.
  • Blood-Based Biomarkers: We are also developing blood tests for markers of neuronal damage, such as Neurofilament light chain (NfL). Elevated NfL levels in the blood indicate that neurons are dying, although this is not specific to Alzheimer’s and can be seen in many neurological conditions. Other markers, such as GFAP (glial fibrillary acidic protein), a marker of astrocyte activation (an inflammatory response in the brain), are also under intense investigation.

It’s important to note a crucial clinical guideline: as of July 30, 2026, we do not recommend screening for these pathological markers in individuals without clinical symptoms. A significant portion of older adults may have some amyloid accumulation without ever developing dementia. Testing asymptomatic individuals could cause undue anxiety and lead to a diagnosis of a disease that may never manifest clinically. The current recommendation is to use these powerful biomarker tests to clarify the diagnosis in people who are already experiencing cognitive changes.

The Complex Reality: Mixed Pathologies in the Aging Brain

While the ATN framework gives us incredible precision for identifying Alzheimer’s disease, the story in the human brain is rarely that simple. The more we learn from large-scale autopsy studies, the more we realize that the brains of older adults, especially those with dementia, are often a “melting pot” of different pathologies. It’s not a matter of choosing one disease; the brain can, and often does, have several at once.
A landmark 2023 study published in The Lancet pulled together data from six large, community-based autopsy studies to illustrate this very point. This research provides a stunning visual representation of how common it is for multiple neuropathologies to coexist.
Let’s break down the common culprits found in the aging brain:

• Amyloid Plaques (Alzheimer’s Pathology): The classic extracellular plaques.
• Tau Tangles (Alzheimer’s Pathology): Measured by Braak staging, which grades the severity and spread of tangles throughout the brain.
• Cerebrovascular Disease: Evidence of microinfarcts (tiny strokes) and macroinfarcts (larger strokes). This is the pathology underlying what is often called “vascular dementia.”
• Lewy Bodies: Abnormal clumps of a protein called alpha-synuclein. When found in the cortex, they cause Lewy Body Dementia. When found in the brainstem, they are the hallmark of Parkinson’s Disease.
• LATE-NC (Limbic-predominant Age-related TDP-43 Encephalopathy): A more recently identified pathology involving a protein called TDP-43, which is also associated with some forms of frontotemporal dementia (FTD) and ALS. It typically affects the oldest-old and impacts memory centers.

What the Autopsy Studies Reveal

When researchers examined the brains, they found that having only one of these pathologies was less common than having several.

• “Pure” Pathologies: A relatively small number of individuals had just one type of pathology. For instance, some had only amyloid plaques, some had only tau tangles, and others had only evidence of vascular disease or Lewy bodies.
• The Co-occurrence of Pathologies: The majority of individuals, especially those with dementia, had two, three, or even more of these pathologies simultaneously.
  • The most common combination causing dementia was, unsurprisingly, amyloid plaques and tau tangles (classic Alzheimer’s).
  • However, it was extremely common to find these combined with other issues. For example, a person could have classic Alzheimer’s pathology plus significant vascular damage. This is often termed “mixed dementia.”
  • Another common finding was the “triple threat”: amyloid, tau, and Lewy bodies all present in the same brain.
  • We also see patients in our clinic who present with symptoms more typical of Frontotemporal Dementia (FTD), like personality changes and disinhibition, yet their biomarkers are positive for Alzheimer’s disease (A+T+). This indicates they likely have both pathologies.

Clinical Implications of Mixed Pathologies

This reality of mixed pathologies has profound implications for both diagnosis and treatment.

1. Explains Symptom Variability: It helps explain why two people with a diagnosis of “Alzheimer’s” can have very different symptoms and disease trajectories. One person’s disease might be driven primarily by amyloid and tau, while another’s is complicated by vascular damage or Lewy bodies, leading to a different clinical picture.
2. Challenges “One-Drug, One-Cure” Approaches: It underscores why a single “magic bullet” targeting a single pathway (e.g., amyloid alone) may not be a complete solution for many people. If a person’s cognitive decline is being driven by amyloid, vascular damage, and inflammation, a truly effective treatment plan must address all of these contributing factors.
3. Reinforces the Need for a Comprehensive, Integrative Approach: This is where our clinic’s philosophy truly shines. Recognizing that dementia is a complex, multifactorial syndrome means we must approach it from multiple angles. We cannot just focus on the neuropathology in isolation. We must also consider the systemic factors that contribute to brain health and resilience, such as inflammation, metabolic dysfunction, nutritional deficiencies, and vascular health.

This is why our integrated model, combining Dr. Cardenas’s medical oversight with my expertise in chiropractic and functional medicine, is so crucial. We look beyond the brain and consider the whole person.

Building a Diagnosis: Our Stepwise Clinical Pathway

Cognitive decline is no longer a single-track disease entity with narrow solutions. The literature now recognizes heterogeneous Alzheimer’s disease pathologies, overlapping proteinopathies, vascular contributions, inflammatory drivers, and toxic exposures. This shifts how we evaluate, diagnose, and treat. Our team at Injury Medical Clinic aims to meet this complexity with compassion and precision, leveraging shared decision-making with patients and care partners and applying tiered testing strategies that begin with high-yield, accessible steps and escalate only when clinically meaningful.

How I Start: Building a Symptom Story That Guides Precise Testing

Every evaluation begins not with a test, but with a conversation. A rich history is paramount because every symptom is a clue to an underlying physiological process. I ask about onset, tempo, triggers, and alleviating factors. I explore associated psychiatric, sleep, autonomic, and pain features.

• The Importance of a Secondary Historian: With cognitive decline, self-report can miss key changes. A trusted person—often a spouse, adult child, or close friend—helps fill in the gaps. This secondary historian can report early executive changes, social withdrawal, or disinhibition that the patient may not perceive. Their observations stabilize the timeline and reveal patterns like increased repetition, lost items, and inconsistent task completion. We keep information flow clinician-directed (incoming to us) to protect privacy while gathering actionable data.
• What I Listen For:
  • Attentional lapses versus encoding failures. Attention deficits often degrade memory retrieval because the initial information capture is weak. Is the person distracted, or are they truly unable to form a new memory?
  • Executive dysfunction signatures: Are there planning errors, judgment lapses, disorganization, or difficulty shifting between tasks?
  • Language changes: These could include word-finding pauses (anomia), using the wrong words (paraphasias), or a slippage in comprehension.
  • Visuospatial issues: Is the person getting lost, misjudging distances, or having trouble with navigation or configurations?
  • Neuropsychiatric features: Apathy, irritability, anxiety, depression, sleep fragmentation, features of REM sleep behavior disorder, or psychosis in later stages are all crucial clues.
  • Functional decline: How is this affecting basic Activities of Daily Living (ADLs) like bathing and dressing, and Instrumental ADLs (iADLs) like managing finances, medications, or transportation?
• How History Informs Staging: We translate this narrative into clinical categories—unimpaired, subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia—and then stage the dementia as mild, moderate, or severe. This aligns with ICD-10 coding and influences treatment selection.

Neurological and Neuropsychiatric Assessment: What It Reveals

• Neurological Exam Expectations: In early cognitive decline, I rarely expect pronounced deficits on deep tendon reflexes, cerebellar tests, or gross motor function. However, subtle findings—such as changes in gait speed, mild rigidity, or asymmetric arm swing—can suggest mixed degenerative or vascular contributions.
• Validated Mood and Anxiety Tools: Many common scales (e.g., PHQ-9 for depression, GAD-7 for anxiety) are helpful but can be imperfect for middle-stage cognitive impairment. I often consider neuropsychiatric inventories designed for dementia populations and adapt their administration, with caregiver input, to maintain validity.
• Why Mood Matters Physiologically:
  • Depression can reduce activity in the dorsolateral prefrontal cortex, which governs attention, thereby compounding memory difficulties.
  • Anxiety increases sympathetic tone, which fragments sleep and elevates stress hormones, reducing the slow-wave sleep needed for glymphatic clearance of brain waste products like amyloid and tau.
• Sleep Assessment:
  • Obstructive sleep apnea (OSA) causes intermittent hypoxia (low oxygen levels), increases oxidative stress, and disrupts slow-wave sleep. This combination severely impairs memory consolidation and the brain’s glymphatic waste clearance system.
  • Insomnia and circadian misalignment reduce hippocampal neurogenesis and plasticity, directly increasing cognitive complaints.

Functional Measurement: Translating Symptoms into Safety and Independence

• ADLs and iADLs Capture Real-World Capacity. I specifically measure:
  • Medication management, finances, meal preparation, driving safety, and household organization.
  • Fall risk, gait stability, and navigational competence.
• Why Function Guides Care:
  • Early executive decline can precede changes on memory tests, often affecting iADLs first.
  • Functional data define our rehabilitation priorities—balance training, dual-task walking, strength conditioning—and inform crucial family planning and legal steps.

Neuropsychological Testing: Mapping the Cognitive Domains

• What It Reveals: Neuropsychology provides a detailed map of cognitive domains, including attention, processing speed, executive function, memory encoding and retrieval, language, and visuospatial skills.
• Why I Refer:
  • It sharpens the differential diagnosis, helping distinguish Alzheimer’s-predominant encoding deficits from the frontal-executive patterns seen in vascular cognitive impairment or Lewy body spectrum disorders.
  • It establishes a precise baseline for longitudinal comparison and for measuring the impact of our treatments.
  • In many communities, neuropsychology is more available than specialty imaging or CSF studies, making it a practical and highly informative first-line escalated test.

Structural Neuroimaging: MRI Is Preferred

• Why I Start with Structural Imaging:
  • An MRI can reveal patterns of hippocampal atrophy, white matter hyperintensities (WMH) indicating small vessel disease, microbleeds, and disproportionate cortical thinning.
  • A CT scan can be used when MRI is contraindicated or inaccessible; it can identify atrophy and gross vascular lesions.
• Physiological Insights from Imaging:
  • Vascular burdens (WMH, lacunar infarcts) correlate with slowed processing speed and executive dysfunction.
  • The presence of microbleeds raises caution for the use of anticoagulation and influences risk-benefit discussions for amyloid-targeted therapies.
  • Hippocampal atrophy aligns strongly with the memory encoding deficits characteristic of Alzheimer’s pathology.

Tiered Laboratory Studies: Correcting Reversible Contributors First

• Tier 1 Tests Are High-Yield: Before delving into complex biomarkers, we must rule out and correct reversible contributors. These basic labs are essential because systemic health shapes brain resilience.
  • Thyroid function (TSH, free T4): Hypothyroidism can mimic dementia by reducing overall metabolic activity.
  • Vitamin B12 and possibly methylmalonic acid: Deficiency impairs myelin integrity and neuronal metabolism.
  • Complete blood count and comprehensive metabolic panel: These can detect anemia, hepatic dysfunction, or renal dysfunction that may affect cognition or medication metabolism.
  • Inflammatory markers (e.g., hs-CRP): Chronic inflammation can perturb synaptic function and increase harmful microglial activation in the brain.

New Clinical Practice Guidance: The Detect AD Framework

As our tools have advanced, so have our clinical guidelines. The Detect AD guidelines, published in 2025 and supported by the Alzheimer’s Association, provide a modern decision pathway for clinicians.

• Core Evaluation Elements: These guidelines highlight the importance of history, functional measures, neuropsychiatric assessment, validated mental status tools, neuropsychology referrals, structural imaging, tiered labs, and the optional use of biomarkers.
• Communication is Central: The framework emphasizes setting expectations with patients and care partners, including them in the diagnostic process, and co-creating a shared care plan.
• Primary Care and Subspecialty Roles: Most cognitive care begins in primary care. The guidelines provide clear indications for when to consult a dementia subspecialist.
• Decision Tree Logic: The evaluation should unfold over multiple visits to avoid overwhelming patients and to document changes over time. It starts with concern screening and moves through tiered testing, with confidence thresholds guiding each escalation.

Staging and ICD-10 Coding: Why Categorization Supports Care

• Unimpaired vs. SCD, MCI, and Dementia:
  • Subjective Cognitive Decline (SCD): This involves a patient-reported decline without objective abnormalities on testing. Here, we monitor, optimize lifestyle, and address modifiable risks.
  • Mild Cognitive Impairment (MCI): This is characterized by objective impairment in one or more domains with preserved independent function. We deploy cognitive rehabilitation, risk reduction, and sometimes pharmacotherapy.
  • Dementia: This involves cognitive impairment plus functional loss. We stage it as mild, moderate, or severe and integrate medical, behavioral, and caregiver supports.
• Why Coding Matters: Accurate staging and etiology categorization are not just administrative tasks. They support appropriate referrals, ensure coverage for necessary tests, and guide effective care planning.

The Landscape of Alzheimer’s Therapeutics: From Symptomatic to Disease-Modifying

The past decade has been transformative in Alzheimer’s therapeutics. We have moved from managing symptoms to directly targeting the underlying pathology. However, understanding the nuances of these treatments is critical for setting realistic expectations.

Why Drug Development Has Been So Challenging

I often begin by setting expectations with families. The history of Alzheimer’s drug development is fraught with failure. A seminal review by Dr. Jeffrey Cummings and colleagues synthesized a decade of trials and revealed an astonishingly low success rate.

• Approximately 244 compounds were assessed over ten years.
• Only about 2% of compounds moved from Phase 2 to Phase 3 trials.
• Of those that completed Phase 3, only about 0.4% achieved FDA approval.

This history contextualizes why the recent approvals of amyloid-targeting therapies generated cautious optimism. They are not miracle cures. They are targeted tools that, when used in the right patient at the right time with the right safeguards, can produce statistically and clinically meaningful slowing of decline.

Understanding Clinical Trial Measures in Real-World Practice

Clinical research uses standardized measures that most front-line clinicians don’t use during routine visits. As a practitioner, I need to translate these scales into what they mean for daily function and caregiver experience.

• Mini-Mental State Examination (MMSE): A 30-point bedside test of cognition. A small positive shift (e.g., +0.4 points) on a 30-point scale may not seem dramatic, but if it reflects stabilization rather than decline, it can translate into preserved independence.
• Clinical Dementia Rating-Sum of Boxes (CDR-SB): A structured, caregiver-informed interview covering six functional domains. This scale maps more directly to real-world function. A modest difference on the CDR-SB can correspond to meaningful preservation of independence, such as fewer hours of care needed per day.
• Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): A multi-item battery assessing memory and language, where higher scores mean worse performance. Benefit on this scale often reflects “less decline” rather than dramatic improvement.

The realistic promise for most agents is slower worsening. If a placebo group declines by an average of 1 MMSE point in 6 months, and a treated group stabilizes or improves slightly, the “relative improvement” is what matters. This stabilization could mean a preserved ability to manage dressing, safer ambulation, or fewer daily crises.

The Root Causes of Pain-Video

Symptomatic Therapies: Why They Still Matter

Acetylcholinesterase Inhibitors (AChEIs)

• Mechanism and Rationale: In Alzheimer’s, cholinergic deficits impair attention and memory. Acetylcholinesterase inhibitors (AChEIs), such as donepezil and rivastigmine, inhibit the breakdown of acetylcholine, a key neurotransmitter involved in attention. By bolstering this system, we can improve the brain’s ability to attend to information, which is a prerequisite for encoding memories. The brain cannot remember what it did not properly attend to.
• Common Adverse Effects:
  • Gastrointestinal (GI): Nausea and diarrhea are frequent but often transient. We manage this by titrating the dose slowly (e.g., starting at 5 mg of donepezil) or by using transdermal formulations such as the rivastigmine patch to minimize peaks and valleys in drug levels.
  • Cardiac: Bradyarrhythmias (slow heart rate) and syncope (fainting) can occur. In older adults, recurrent syncope warrants discontinuation, as per the Beers criteria for potentially inappropriate medication use.
  • Clinical Reasoning: I deploy AChEIs to support attentional circuits and improve the quality of neural signaling. We monitor closely for side effects and prioritize shared decision-making, as tolerance and functional gains vary widely.

NMDA Receptor Antagonism: Memantine

• Mechanism: Memantine works by a different mechanism. It modulates pathologic glutamatergic excitotoxicity, a process where excessive stimulation by the neurotransmitter glutamate causes neuronal stress and damage. By acting as an antagonist at the NMDA receptor, memantine helps reduce this toxic “noise” in the brain.
• Where It Shines: Memantine’s benefits are often seen less in raw cognitive scores and more in preserving function and stabilizing behavior, particularly in activities of daily living.
• Combination Therapy (Memantine + AChEI): The evidence suggests that combining an AChEI with memantine often delivers the most consistent functional preservation. Patients on both agents tend to show the slowest functional decline compared to either monotherapy or placebo.

Disease-Modifying Therapies: The New Era of Amyloid-Targeted Biologics

The newest Alzheimer’s drugs are monoclonal antibodies that target beta-amyloid. These agents aim to modify the underlying disease process.

Advanced Biomarkers: The Gateway to Disease-Modifying Therapies

• Blood-Based Biomarkers: Today, blood-based biomarkers are changing first-line decision-making. Key analytes include phosphorylated tau variants, notably p-tau217, which has high accuracy for detecting Alzheimer’s pathology. These tests are fast, less invasive, and more accessible, serving as a powerful triage tool. A positive result can help justify more definitive (and expensive) confirmatory testing.
• Confirmatory Testing: Currently, initiating anti-amyloid therapy still requires confirmation of amyloid positivity via amyloid PET scan or CSF analysis.

Lecanemab and Donanemab: Progress with Monitoring Duties

Two FDA-approved therapies, lecanemab and donanemab, have shown a statistically significant slowing of cognitive decline in early-stage Alzheimer’s disease. However, they come with significant responsibilities.

• What is ARIA? Both agents carry a risk of Amyloid-Related Imaging Abnormalities (ARIA).
  • ARIA-E (Edema/Effusion): This involves vasogenic edema, likely reflecting an inflammatory response as the antibody clears amyloid from the walls of blood vessels.
  • ARIA-H (Hemosiderin/Microhemorrhage): This refers to microbleeds in fragile vessels, also likely linked to the amyloid clearance process, which stresses the vessel walls.
• The Role of APOE Genotype: The risk of ARIA is strongly influenced by a person’s APOE genotype.
  • Individuals with two copies of the APOE4 allele (E4/E4 homozygotes) have a substantially higher ARIA incidence.
  • Those with one copy (E3/E4 heterozygotes) have an intermediate risk.
  • Therefore, APOE genotyping is now a standard of care before starting these therapies to inform risk stratification and shared decision-making.
• Monitoring Realities: Initiating these therapies requires a significant logistical commitment, including regular infusions and a strict schedule of safety MRIs, especially during the initial phase of treatment. A recent update to safety protocols includes an MRI checkpoint after the second infusion for all treated patients to detect serious ARIA cases earlier.

Neuropsychiatric Symptoms: The Hidden Drivers of Distress

If cognition is the “headline” of dementia, then neuropsychiatric symptoms (NPS) are the “story.” Agitation, irritability, anxiety, apathy, depression, delusions, and hallucinations are what most often drive caregiver strain, emergency visits, and institutionalization.

A Root-Cause Checklist Before Prescribing

Before jumping to medication, we conduct a thorough root-cause analysis. NPS are often a form of communication for an unmet need.

• Physical Drivers:
  • Pain: Is there untreated arthritic pain, neuropathic discomfort, or a cervicogenic headache?
  • Infections: Urinary tract infections are a common culprit.
  • Constipation, dehydration, or metabolic issues.
  • Sensory Impairments: Is the person not wearing their glasses or hearing aids? Is the room poorly lit?
• Environmental Drivers:
  • Overstimulation: Too much noise, clutter, or chaos.
  • Understimulation: A barren environment can lead to boredom and agitation.
  • Novelty: Unfamiliar environments, such as hospitals, can be highly disorienting.
• Psychological and Social Drivers:
  • Unmet Needs: Hunger, thirst, loneliness, or a lack of structured activity.
  • Fear or Insecurity: Separation from a familiar caregiver or changes in routine.

A Therapeutic Ladder for NPS Management

• Step 1: Non-Pharmacologic Foundation: Structure the day, optimize the sensory environment, provide meaningful engagement (like music therapy), and ensure physical comfort.
• Step 2: Targeted Pharmacology: If medication is needed, we address the dominant symptom.
  • Anxiety/irritability: Consider SSRIs.
  • Psychosis or severe, dangerous agitation: Antipsychotics may be necessary, but they are used judiciously after other strategies have failed due to their significant risks in this population.
• Step 3: Pharmacogenetic Testing: To avoid a lengthy trial-and-error process with medications, we often use pharmacogenetic testing. This can help tailor dosing and narrow the field of potential drugs, moving more quickly to an effective and well-tolerated option.

The Role of Integrative Chiropractic Care in Brain Health

When people hear “chiropractic,” they often think of back and neck pain. While that is a core part of our practice, modern, evidence-based chiropractic care —especially when integrated with functional medicine —is fundamentally about optimizing nervous system function—the master controller of the entire body, including the brain. Our collaborative approach with Dr. Cardenas ensures that all treatments are medically sound and integrated into a cohesive plan.

1. Optimizing Cerebrospinal Fluid (CSF) Flow

The brain is bathed in CSF, which delivers nutrients and, crucially, clears metabolic waste via the glymphatic system. This “brainwashing” process is most active during deep sleep and is vital for clearing toxins such as beta-amyloid and tau before they can form plaques and tangles.

• The Chiropractic Connection: CSF flow is influenced by the biomechanics of the skull and cervical spine (neck). Spinal misalignments, or vertebral subluxations, particularly in the upper neck, can impede the normal flow of both blood and CSF to and from the brain.
• Our Approach: Through gentle, specific chiropractic adjustments, we work to restore proper motion and alignment. This can help normalize biomechanical function, potentially improving CSF flow dynamics and enhancing glymphatic system efficiency. Dr. Cardenas’s medical oversight ensures that this approach is safe, especially for older adults who may have other conditions such as osteoporosis or vascular disease.

2. Reducing Systemic and Neuro-inflammation

Inflammation is a key driver in Alzheimer’s progression. Chronic inflammation throughout the body (systemic inflammation) can cross the blood-brain barrier and worsen inflammation in the brain (neuroinflammation).

• The Chiropractic Connection: Research has shown that chiropractic adjustments can modulate inflammatory pathways. By reducing physical stress on the nervous system, adjustments can help downregulate pro-inflammatory cytokine production.
• Our Functional Medicine Approach: As a certified Functional Medicine practitioner, I also address other root causes of inflammation through:
  • Dietary Interventions: An anti-inflammatory diet rich in omega-3 fatty acids and phytonutrients.
  • Gut Health: A “leaky gut” can allow inflammatory molecules into the bloodstream, affecting the brain. We use advanced testing to assess gut health and implement protocols to heal the gut lining.

3. Improving Proprioception and Reducing Fall Risk

Proprioception is the body’s sense of its position in space. It is vital for balance and coordinated movement. As dementia progresses, individuals are at a much higher risk of falls, which can be devastating.

• The Chiropractic Connection: The joints of the spine, particularly in the neck, are rich in proprioceptive receptors. Spinal dysfunction can disrupt the flow of accurate sensory information to the brain. Adjustments can restore normal joint mechanics, improving the quality of these signals.
• Our Rehabilitative Approach: At Injury Medical Clinic, we integrate chiropractic adjustments with targeted rehabilitation exercises to improve balance, gait, and strength. This not only reduces fall risk but also provides the brain with rich sensory stimulation, helping to maintain neural pathways.

4. Supporting Autonomic Nervous System Regulation

The autonomic nervous system (ANS) controls all our involuntary functions, with the “fight-or-flight” sympathetic branch and the “rest-and-digest” parasympathetic branch in balance. Chronic stress leads to sympathetic dominance, a state associated with increased inflammation and poor vascular health—all risk factors for cognitive decline.

• The Chiropractic Connection: Nerves controlling the ANS exit from the spinal column. Spinal dysfunction can irritate these nerves. Heart rate variability (HRV), a key indicator of autonomic balance, has been shown to improve following chiropractic adjustments. By helping shift the body toward a more balanced parasympathetic state, we can support better sleep, digestion, and cardiovascular health.

Our Multidisciplinary Model in El Paso: Medical Oversight and Functional Integration

Our model at Injury Medical Clinic PA is built on collaboration.

• Dr. Maria Guadalupe Cardenas, MD (Internal Medicine): As our Medical Director, Dr. Cardenas provides the crucial medical oversight for our entire care pathway. She diagnoses and manages internal medicine comorbidities, guides all medication strategies (including AChEIs, memantine, and amyloid-targeting therapies), oversees lab and imaging workups, provides genetic risk counseling, and ensures safety in complex polypharmacy contexts.
• Dr. Alex Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST (Chiropractic, Advanced Practice Nursing, Functional Medicine): I lead the chiropractic and neuromusculoskeletal care, functional medicine coordination, and integrative lifestyle implementation. I focus on pain trajectories, mobility, fall risk, and the co-development of behavioral strategies with caregivers.

This MD-DC partnership works because it addresses the whole person. Internal medicine anchors safety, pharmacology, and comorbidity control. Chiropractic and rehabilitation translate small cognitive gains into preserved independence by reducing pain, improving mobility, and enhancing comfort. Functional medicine tools glue the plan together by optimizing sleep, inflammation, nutrition, and daily rhythms.

Conclusion: A Human-Centered, Evidence-Based Pathway

We are living in a pivotal era for dementia care. Amyloid-targeted therapies are not cures, but they are meaningful tools for slowing decline in selected patients. At Injury Medical Clinic PA, our goal is to combine these rigorous, modern diagnostics with compassionate, individualized care. Under Dr. Cardenas’s internal medicine oversight, our integrative chiropractic and rehabilitation framework addresses the complex physiology of cognitive decline—vascular, metabolic, inflammatory, and neuromusculoskeletal—while always respecting patient choices and family goals.
The most powerful word in cognitive care may not be “cure,” but “stable.” Stability—of sleep, mood, pain, gait, and daily function—is what keeps families together and preserves quality of life. Our team in El Paso is committed to translating the best available evidence into that stability, helping patients and families navigate a challenging landscape with clarity, confidence, and support.

References

• Alzheimer’s Association. (2025). Detect AD clinical practice guidelines for primary care and dementia specialists. Alzheimer’s & Dementia.
• Aricept (donepezil) early phase III trials in Alzheimer’s disease. (1998). Randomized, double-masked, placebo-controlled studies using MMSE, ADAS-Cog, and CDR measures.
• Beers criteria for potentially inappropriate medication use in older adults. (Latest update). American Geriatrics Society.
• Bherer, L., Erickson, K. I., & Liu-Ambrose, T. (2013). A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. Frontiers in Aging Neuroscience, 5, 54.
• Cummings, J. L. (2021). Lessons from Alzheimer’s disease drug failures: Translating biology into clinical benefit. Nature Reviews Neurology.
• Cummings, J., et al. (2014). Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures. Alzheimer’s Research & Therapy, 6(4), 37.
• Cummings, J., et al. (2016). Alzheimer’s disease drug development pipeline: 2016. Alzheimer’s Research & Therapy, 8(1), 39.
• Cummings, J. L., et al. (2025). Alzheimer’s disease drug development pipeline 2025. Alzheimer’s & Dementia.
• Farlow, M. R., et al. (2010). Memantine in moderate-to-severe Alzheimer’s disease: A review of efficacy and safety. Journal of Alzheimer’s Disease.
• Functional medicine approaches to cognitive health: Nutrition, inflammation, and metabolic optimization. (Review).
• Hansen, R. A., et al. (2008). Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis. Archives of Neurology.
• Howard, R., et al. (2012). Donepezil and memantine for moderate-to-severe Alzheimer’s disease. New England Journal of Medicine.
• Iadecola, C. (2013). The pathobiology of vascular dementia. Cold Spring Harbor Perspectives in Medicine, 3(1), a006295.
• 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.
• Jack, C. R., Jr., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 9(1), 119-128.
• Karikari, T. K., et al. (2020). Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease. The Lancet Neurology, 19(5), 422–433.
• Kuller, L. H., & Lopez, O. L. (2016). Blood pressure and cognitive impairment. Hypertension, 68(2), 331–333.
• Livingston, G., et al. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413–446.
• McKhann, G. M., et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the NIA-AA workgroups. Neurology.
• Mintun, M. A., et al. (2021). Donanemab in early Alzheimer’s disease. New England Journal of Medicine, 384(18), 1691–1704.
• Nelson, P. T., Brayne, C., Flanagan, M. E., Kukull, W. A., & Jicha, G. A. (2023). The spectrum of brain pathologies in aged persons with and without dementia. The Lancet, 402(10403), 706-719.
• Neuropsychological testing in MCI and dementia: Domain profiling and clinical utility. (Review).
• Olin, J., & Schneider, L. (2002). Galantamine, rivastigmine, and donepezil in the treatment of Alzheimer’s disease. Clinical Therapeutics.
• Palmqvist, S., et al. (2020). Performance of plasma P-tau217 as a biomarker for Alzheimer disease. JAMA, 324(8), 772–781.
• Petersen, R. C., et al. (2018). Practice guideline update: Mild cognitive impairment. Neurology, 90(3), 126–135.
• Rabinovici, G. D. (2019). The role of amyloid PET in Alzheimer’s disease. JAMA Neurology, 76(2), 134–136.
• Raina, P., et al. (2008). Effectiveness of cholinesterase inhibitors and memantine for Alzheimer’s disease: A systematic review and meta-analysis. BMJ.
• Roy, R. A., Boucher, J. P., & Comtois, A. S. (2009). Heart rate variability modulation after manipulation in healthy subjects. Journal of Manipulative and Physiological Therapeutics, 32(4), 277–286.
• Salloway, S., et al. (2022). Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials. Acta Neurologica Scandinavica, 145(3), 232–243.
• Sims, J. R., et al. (2023). Donanemab in early symptomatic Alzheimer’s disease: The TRAILBLAZER-ALZ 2 trial. JAMA, 330(6), 512–520.
• Sleep and cognition in aging: Glymphatic system and slow-wave sleep mechanisms. (Review).
• SPRINT MIND Investigators (2019). Effect of intensive blood pressure control on probable dementia. JAMA, 321(6), 553–561.
• Tariot, P. N., et al. (2004). Memantine treatment in patients with moderate to severe Alzheimer’s disease already receiving donepezil: A randomized controlled trial. Archives of Neurology.
• Teodorczyk-Injeyan, J. A., McGregor, M., & Triano, J. J. (2010). The effect of spinal manipulation on the production of inflammatory cytokines in a cohort of asymptomatic subjects: A pilot study. Journal of Manipulative and Physiological Therapeutics, 33(8), 582-588.
• van Dyck, C. H., et al. (2023). Lecanemab in early Alzheimer’s disease. New England Journal of Medicine, 388(1), 9–21.
• Vascular cognitive impairment and white matter disease. (Review).
• Winblad, B., et al. (2007). Memantine in moderate to severe Alzheimer’s disease: a meta-analysis. Dementia and Geriatric Cognitive Disorders.
• Yaffe, K., et al. (2014). Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia. JAMA Internal Medicine, 173(20), 1999–2006.

Note: For clinical perspective and integrative care philosophy by Dr. Alexander Jimenez, see:

• Injury Medical Clinic PA – ChiroMed.com
• Dr. Alex Jimenez on LinkedIn

SEO Tags: Alzheimer’s disease, dementia, Dr. Alex Jimenez, Dr. Maria Guadalupe Cardenas, integrative chiropractic care, functional medicine, ATN framework, beta-amyloid, tau protein, neuroinflammation, mixed pathology, El Paso, Injury Medical Clinic, brain health, cerebrospinal fluid, glymphatic system, proprioception, autonomic nervous system, vertebral subluxation, disease-modifying therapy, cognitive decline, mild cognitive impairment, dementia evaluation, Detect AD guidelines, acetylcholinesterase inhibitors, donepezil, rivastigmine, neuropsychological testing, structural MRI, amyloid PET, CSF biomarkers, APOE genotyping, sleep apnea cognition, vascular cognitive impairment, rehabilitation, shared decision-making, memantine, NMDA receptor antagonist, CDR-SB, ADAS-Cog, MMSE, neuropsychiatric symptoms, agitation, pharmacogenetic testing, fall prevention, dementia sleep, caregiver stress, multidisciplinary clinic, lecanemab, donanemab, ARIA risk, p-tau217, blood-based biomarkers, dementia care navigation, cost-effectiveness in Alzheimer’s therapies, evidence-based dementia care