#164 - Amanda Smith, M.D.: Diagnosing, preventing, and treating Alzheimer's disease, and what we can all learn from patients with dementia
Dr. Amanda Smith, a geriatric psychiatrist, discusses Alzheimer's disease diagnosis, the drug pipeline (including adecanumab), and the critical role of supporting patients and caregivers. She also shares insights on healthy aging and life philosophy.
Deep Dive Analysis
14 Topic Outline
Introduction to Geriatric Psychiatry and Alzheimer's Disease
Developing a Passion for Geriatric Psychiatry
Behavioral Components of Dementia and Psychiatric Care
Clinical Definition and Diagnosis of Dementia
Role of Imaging and Biomarkers in Dementia Diagnosis
Pathology of Amyloid and Tau in Alzheimer's Disease
Differentiating Alzheimer's Disease from Lewy Body Dementia
Evolution of Alzheimer's Diagnosis and Treatment Over 20 Years
Psychiatric Support for Dementia Patients and Caregivers
Navigating Grief and End-of-Life Discussions in Dementia
Current Landscape of Alzheimer's Clinical Trials and Drug Pipeline
Challenges in Alzheimer's Drug Development and Outcome Measures
Aducanumab: A Monoclonal Antibody for Alzheimer's Disease
Defining Healthy Aging and Life Philosophy with Dementia Insights
8 Key Concepts
Dementia
An umbrella term describing changes in memory and other cognitive areas that represent a decline from a person's previous level of function and interfere with their day-to-day activities. Alzheimer's disease is the most common cause, but many other conditions can lead to dementia.
Alzheimer's Disease (Pathological Definition)
Pathologically, Alzheimer's disease is defined by the presence of amyloid plaques and tau tangles in the brain. Amyloid buildup can begin 10-20 years before cognitive symptoms appear, while the spread of tau tangles correlates more closely with the onset and progression of symptoms.
Lewy Body Dementia (LBD)
A type of dementia characterized by a classic triad of symptoms: fluctuating cognitive impairment (memory and thinking issues that vary day-to-day), Parkinsonism (motor symptoms like stiffness, shuffling gait, reduced arm swing), and prominent visual hallucinations. Patients often also experience REM sleep behavior disorder.
Amyloid-Related Imaging Abnormalities (ARIA)
Changes observed on MRI scans, specifically brain edema (ARIA-E) or microhemorrhages (ARIA-H), that can occur in patients receiving anti-amyloid drugs. APOE4 carriers are known to have a higher risk of developing ARIA.
Symptomatic Treatments (Dementia)
Medications that help manage or slow cognitive decline and improve memory and thinking by affecting neurotransmitters, but they do not target the underlying disease pathology. Current FDA-approved drugs for Alzheimer's are all symptomatic treatments.
Disease Modifying Treatments (Dementia)
Drugs designed to target the root causes of Alzheimer's disease, such as the abnormal accumulation of amyloid or tau proteins. The goal of these treatments is to remove these pathological proteins from the brain, hoping to halt or reverse cognitive decline.
Preclinical Alzheimer's
A stage identified through advanced imaging where individuals have amyloid buildup in their brains but have not yet developed any noticeable memory or cognitive symptoms. This stage is a critical target for prevention trials aimed at stopping the disease before it manifests clinically.
Mild Cognitive Impairment (MCI)
A transitional stage between normal age-related cognitive changes and dementia, where individuals experience mild but measurable problems with memory, language, thinking, or judgment. Despite these symptoms, they generally maintain their ability to perform daily activities.
12 Questions Answered
Dr. Smith's interest stemmed from growing up with active grandparents who owned a nursing home, and later, during medical school, observing ageism and the pathological aspects of aging, which inspired her to advocate for and treat the elderly.
Dementia is an umbrella term for changes in memory and other cognitive areas, representing a decline from previous function that interferes with daily life, and it has many underlying causes.
Diagnosis relies heavily on a thorough clinical interview with the patient and a separate interview with an observer (like a spouse or adult child), cognitive testing to identify patterns, brain imaging (MRI, FDG PET) to rule out other causes and look for specific changes, and lab tests to exclude reversible causes of memory loss.
Normal forgetfulness or distraction is usually an exception, often linked to stress or lack of sleep, whereas in dementia, memory issues become frequent, intense, and a consistent part of daily function.
The APOE4 genotype increases the risk of developing Alzheimer's disease and can influence responses to treatments and lifestyle interventions, but it is not diagnostic, meaning carriers may not develop the disease and non-carriers still can.
Lewy body dementia typically presents with a triad of fluctuating cognitive impairment, Parkinsonism (motor symptoms like stiffness and shuffling), and prominent visual hallucinations, often accompanied by REM sleep behavior disorder, whereas Alzheimer's usually starts with progressive short-term memory loss.
Lewy body dementia typically progresses over about 8 years, which can be quicker than Alzheimer's, though Alzheimer's also averages 8-10 years but can be more protracted in some cases.
There's increased public awareness that Alzheimer's is a disease, not normal aging, leading to earlier intervention, a focus on prevention, and a shift in research towards disease-modifying treatments targeting underlying pathology rather than just symptoms.
Psychiatric care addresses common mood and behavioral issues like anxiety, depression, agitation, and psychosis, which affect a majority of dementia patients. It also provides crucial emotional support, education, and practical strategies for caregivers, helping them cope with the challenges and grief associated with the disease.
Challenges include the complexity of the disease, the high cost and long duration of clinical trials, the difficulty in selecting the right patient population (e.g., early vs. late stage), and the need for more objective and sensitive primary outcome measures beyond traditional cognitive tests.
Aducanumab, an anti-amyloid monoclonal antibody by Biogen, is awaiting an FDA decision on June 7th regarding its approval. Its phase 3 trials (Emerge and Engage) had mixed results, leading to debate among scientific and advocacy groups.
Healthy aging involves focusing on the present, maintaining positive relationships, adapting to physical and mental changes by finding new ways to enjoy life, and letting go of regrets, rather than dwelling on past abilities or future declines.
26 Actionable Insights
1. Prioritize Emotional Health, Relationships
Shift your identity and focus towards emotional health and the quality of your relationships, as these aspects are less tied to age-related decline and are key determinants of well-being and happiness throughout life.
2. Cultivate Positive Mindset for Aging
Age successfully by focusing on how you see yourself, fostering positive interactions with the world, nurturing strong relationships, letting go of past losses, and actively focusing on the positive aspects of life.
3. Engage in Aerobic Exercise
Engage in regular aerobic exercise, as a growing body of data shows it can improve cognitive testing scores even in individuals with existing cognitive impairment or full-blown dementia, making it beneficial beyond just prevention.
4. Manage Cardiovascular Risk Factors
Actively manage risk factors like high blood pressure, high cholesterol, smoking, and diabetes to reduce the accumulation of tiny strokes and vascular disease in the brain, which can contribute to cognitive impairment.
5. Act on Life Goals Now
Don’t postpone significant life goals or experiences until retirement, as unforeseen health issues may prevent you from enjoying them; live in the present and pursue what brings you joy now.
6. Reframe Challenging Behaviors
Caregivers should understand that challenging behaviors in loved ones with dementia are symptoms of the disease, not intentional acts to annoy; respond with patience and reframe interactions to reduce personal frustration and improve care.
7. Focus on Present in Alzheimer’s
For both patients and caregivers, prioritize focusing on the present moment and making each day better, rather than dwelling on the inevitable progression of Alzheimer’s, as patients often live in the moment.
8. Regularly Review, Deprescribe Medications
For elderly individuals, especially those with dementia, regularly review all medications with a healthcare professional to identify and deprescribe unnecessary drugs, ensuring treatment targets symptoms with the safest, lowest dose.
9. Seek Early Intervention for Alzheimer’s
Overcome embarrassment or isolation associated with Alzheimer’s symptoms and seek early medical help, as current medications, while not cures, can slow cognitive decline and preserve function for a period.
10. Recognize Alzheimer’s as Treatable Disease
Understand that Alzheimer’s is a disease, not a normal part of aging, and that early intervention and treatment can slow decline and preserve function, encouraging timely help-seeking.
11. Use Positive Reinforcement for Caregiving
When a loved one with dementia resists a necessary task (e.g., showering), use positive reinforcement by offering a favorite reward (e.g., a snack) immediately after the task, rather than engaging in a struggle.
12. Combat Social Isolation
Actively combat social isolation by nurturing relationships and engaging with others, as strong social connections are a crucial determinant of quality of life and emotional well-being as you age.
13. Ensure Separate Interviews for Diagnosis
When seeking a dementia diagnosis, ensure that the patient and an observer (e.g., spouse, adult child) are interviewed separately, as this prevents crucial information from being omitted due to discomfort or desire to protect feelings.
14. Rule Out Reversible Memory Loss
If experiencing memory loss, undergo comprehensive lab tests (e.g., for thyroid disturbance, vitamin deficiencies) to identify and treat any reversible causes before assuming a neurodegenerative condition.
15. Avoid Benzodiazepines for Elderly
For elderly patients with dementia, avoid chronic use of benzodiazepines (e.g., alprazolam, lorazepam) due to their high risk of increasing confusion and significantly raising the incidence of hip fractures.
16. Tailor Prevention Based on APOE
If you know your APOE genotype, use it to inform your approach to preventative measures; while a protective genotype doesn’t eliminate risk, a higher-risk genotype should prompt a more serious commitment to prevention.
17. Adapt Activities to Enjoy Life
Even with a diagnosis or physical limitations, adapt your favorite activities and pursue things you enjoy, rather than giving them up entirely, to maintain quality of life.
18. Seek Support as Caregiver
Caregivers should seek opportunities to vent and talk to others who understand their experiences, as sharing insights and receiving validation can provide significant emotional support and practical advice.
19. Implement Practical Travel Safety
When traveling with a loved one with dementia, implement simple safety measures like having them wear a lanyard with their room number and your cell phone number, allowing for continued enjoyment of activities with necessary adjustments.
20. Differentiate Normal vs. Dementia
When concerned about memory issues, consider the context: stress, poor sleep, and normal aging can cause forgetfulness. True concern arises when memory problems become a daily, frequent, and intense pattern.
21. Cultivate Empathy for Elderly
Develop patience and understanding for elderly patients by considering their life stories and experiences, which can provide context for their current state and foster better care.
22. Challenge Ageism in Healthcare
Be aware of and challenge the tendency to dismiss or ‘brush off’ the elderly, as this can lead to misdiagnosis or inadequate care and reflects an attitude of ageism.
23. Understand APOE Genotype Limitations
Recognize that APOE genotyping is not diagnostic for Alzheimer’s disease and can cause undue worry; its primary utility is in research settings to understand treatment responses and risk, not routine clinical care.
24. Focus on Clinical Outcomes
When evaluating treatments for Alzheimer’s, prioritize clinical outcomes (patient improvement, symptom reduction) over biomarker changes (e.g., amyloid removal), as biomarker success does not guarantee clinical benefit.
25. Be Aware of ARIA Risk
If considering anti-amyloid drugs, be aware of the risk of amyloid-related imaging abnormalities (ARIA), such as brain swelling or microhemorrhages, especially if you are an APOE4 carrier, as this may influence dosing or suitability.
26. Prioritize Prevention for Cure
Understand that prevention trials, which aim to stop Alzheimer’s before symptoms begin, represent the most promising path towards a cure, similar to intervening early in cardiovascular disease.
6 Key Quotes
I realized how quick people are to brush off the elderly. And it kind of lit a fire in me, so to speak, so that, you know, that became my passion.
Amanda Smith
I can't tell you how many times I see a patient and they sit down in my office and I'm like, so what brings you in today? And they're like, my wife, there's nothing wrong with me, I'm fine.
Amanda Smith
It's like grieving for someone while they're still alive.
Amanda Smith
The train had left the station, and it was going to do what it was going to do.
Amanda Smith
Don't wait until I retire to get that beach condo because I might not be able to use it. You know, I'm living now, so do it now.
Amanda Smith
The data, the growing body of data shows that even in people who have cognitive impairment or have full-blown dementia, aerobic activity can actually improve scores on cognitive testing.
Amanda Smith