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Peter Attia MDPeter Attia MD

164 - Diagnosing, preventing, & treating Alzheimer’s disease, & life lessons from dementia patients

Amanda Grant Smith is a geriatric psychiatrist with decades of experience treating patients with dementia and Alzheimer's disease. In this episode, Amanda shares how she developed a passion for geriatric psychiatry as a means to support dementia patients. She explains how to recognize, define, and diagnose dementia—a process that still remains somewhat elusive. They also talk about the significance of ApoE genotype and compare the various forms of dementia including differentiating between Alzheimer’s disease and Lewy body dementia. They discuss the current landscape of clinical trials, the drug pipeline, and talk about a very promising monoclonal antibody directed at amyloid beta that has the potential to be a disease-modifying drug. They conclude with a discussion about how to define “healthy aging” and reflect on how understanding dementia can shape one’s life philosophy. We discuss: 00:00:00 - Intro 00:00:10 - How Amanda developed a passion for geriatric psychiatry; 00:11:17 - Defining and diagnosing dementia and Alzheimer’s disease; 00:21:28 - Medical tests for dementia and their relationship to clinical symptoms; 00:32:50 - The pathology of dementia, and the role of the tau and beta-amyloid protein in Alzheimer’s disease; 00:44:10 - The significance of ApoE genotype, and differentiating Alzheimer’s disease from Lewy body dementia; 00:54:44 - The evolution of Alzheimer’s disease prevention, care, and medications over the last 20 years; 01:06:14 - Psychiatric support for dementia patients (and caregivers) with depression and anxiety; 01:19:03 - Drug pipeline, clinical trials, and major challenges to overcome; 01:29:15 - Redefining Alzheimer’s disease and designing effective trials; 01:41:21 - The promise of monoclonal antibody treatments for Alzheimer’s disease; 01:50:47 - How we should measure outcomes in dementia trials and define “healthy aging”; 02:02:45 - How understanding dementia can reshape our life philosophy; Show notes page: https://peterattiamd.com/amandasmith/ -------- About: The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 30 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more. Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life). Learn more: https://peterattiamd.com Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle

Peter AttiahostAmanda Grant Smithguest
Jun 7, 20212h 11mWatch on YouTube ↗

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At a glance

WHAT IT’S REALLY ABOUT

Geriatric psychiatrist explains Alzheimer's diagnosis, drug trials, caregiving, and living fully despite dementia

  1. Amanda Grant Smith explains that dementia diagnosis rests mainly on separate clinical interviews with the patient and an informant, supported by cognitive testing, MRI, labs, and sometimes PET or CSF tests.
  2. She and Peter Attia discuss amyloid and tau pathology, mixed dementias, the 2011 redefinition of Alzheimer's that allowed preclinical and MCI stages to be studied, and why prevention is the most promising goal.
  3. The conversation covers drug development, including the largely disease-modifying pipeline, early anti-amyloid trials that failed in mild-to-moderate disease, and the Biogen aducanumab FDA decision pending on June 7th.
  4. Smith describes treating behavioral and mood symptoms with careful medication choices and practical caregiver coaching, since caregivers' wellbeing and understanding strongly shape care.
  5. They close on healthy aging, agreeing that focusing on the present, maintaining relationships, avoiding regret, and exercising matter greatly in living well with decline.

IDEAS WORTH REMEMBERING

5 ideas

Diagnosis depends heavily on the clinical story

Smith says the crux of diagnosis is a good interview with the patient and, separately, an informant, because loved ones may withhold key details in front of the patient. Imaging and labs support and rule out other causes.

Amyloid builds up years before symptoms

Smith says amyloid accumulates 10 to 20 years before forgetfulness, and that tau spread correlates more closely with symptoms. Attia compares this to coronary calcification that may never become a heart attack.

The 2011 redefinition changed trial design

Before 2011, Alzheimer's was defined as dementia, so there was no room to test interventions earlier. Amyloid imaging allowed preclinical and MCI stages, enabling prevention trials.

Most dementia pathology is mixed

Smith notes autopsy studies show pure Alzheimer's is less common than mixed cases, with vascular disease the most common additional diagnosis. This supports the relevance of cardiovascular risk factors.

Behavioral symptoms are common and treatable

Smith says about 90% of patients have some behavioral issue, and depression in dementia is as treatable as in anyone else. She favors SSRIs and avoids benzodiazepines because of confusion and hip fracture risk.

WORDS WORTH SAVING

5 quotes

People are terrified of losing their minds and losing their memories. And so that continues to be sort of the biggest motivator in terms of people seeking help.

— Amanda Grant Smith

Because the truth is with Alzheimer's, that's all people have. You know, they have today. They have... you know, 'cause they may not remember tomorrow what happened today. So, um, they're really living in the moment.

— Amanda Grant Smith

Depression in a demented person is just as treatable as depression in a healthy 25-year-old.

— Amanda Grant Smith

I think that's where I see people struggle the most as a psychiatrist and people develop the most depression, is when they spend so much time looking down the road at what's gonna happen or what might happen that they can't enjoy now.

— Amanda Grant Smith

Don't wait. Don't wait until I retire to get that beach condo, 'cause I might not be able to use it, you know? I'm living now, so do it now.

— Amanda Grant Smith

Geriatric psychiatry and ageismClinical diagnosis of dementiaAmyloid, tau, and mixed pathologyLewy body vs. Alzheimer's dementiaBehavioral symptoms and caregiver supportDrug pipeline and aducanumab trialsHealthy aging and regret

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