Curbsiders Internal Medicine Podcast

Episode 511: Alzheimer's Disease — Updates in Diagnosis and Treatment

Release Date: January 12, 2026
Host(s): Dr. Matthew Frank Watto, Dr. Paul Nelson Williams, Dr. Natalie Barrett
Guest: Dr. Halima Amjad, Geriatrician & Dementia Specialist, Johns Hopkins

Episode Overview

This episode features a deep dive into cutting-edge developments in the diagnosis and management of Alzheimer’s Disease. The Curbsiders are joined by Dr. Halima Amjad, who brings her expertise as a dementia specialist and researcher to discuss:

• Nuances of diagnosing Alzheimer's disease, with a focus on differentiating dementia and MCI
• The emerging role, limitations, and interpretation of plasma-based biomarkers
• Considerations for anti-amyloid therapies, including safety, efficacy, and patient selection
• Controversies and unknowns in the field as practice and evidence rapidly evolve

The hosts also share practical tips, reflect on the complexities of real-world care, and discuss ongoing changes in how internal medicine and primary care should approach dementia and Alzheimer’s in 2026 and beyond.

Key Topics & Insights

1. Establishing the Diagnosis: Dementia vs. MCI

(06:41–09:59, 12:37–17:14)

• The importance of detailed cognitive and functional history, especially in trained, high-functioning individuals.
• Deficits in delayed recall and short-term memory (moCA/MMSE) are key tip-offs for Alzheimer’s over normal aging.
• Functional history is crucial to distinguish MCI (intact function) from early or mild dementia (some new impairment).

  “It is really the functional impairment that differentiates MCI — mild cognitive impairment — from mild or early stage dementia.”
  —Dr. Halima Amjad (13:20)

• Imaging (especially MRI findings like mesial temporal lobe atrophy) can be suggestive but not diagnostic.
• Co-existing vascular risk factors and imaging findings are common; clinicians must consider them but not over-attribute.

2. Plasma Biomarkers in Alzheimer’s Diagnosis

(23:31–34:12)

• Blood-based biomarkers (notably P-tau217 and the Aβ42/40 ratio) are becoming available but are currently only validated for people with objective cognitive impairment—not for asymptomatic patients or "worried well."

  “All the guidelines… are only indicated for checking them in people who have evidence of cognitive impairment… It is not for the worried well…”
  —Dr. Halima Amjad (23:41)

• Direct-to-consumer testing is rising; clinicians must be prepared to counsel on limitations and appropriate use.
• Blood biomarkers are screening tests — confirmation (e.g., amyloid PET, CSF) is still required before anti-amyloid therapy.
• APOE genotyping often comes up, especially with anti-amyloid therapy eligibility and patient/family concern. It increases risk but is not determinative.

Notable Quote:

“It is okay to defer [blood biomarkers] to a specialist if you’re not comfortable yet... What will we do with the results?”
—Dr. Halima Amjad (25:50)

3. Anti-Amyloid Therapies — Who, When, and How?

(42:37–51:55, 45:14, 52:24–62:47)

• These treatments (e.g., lecanemab, donanemab) are approved only for mild cognitive impairment or early Alzheimer’s—NOT for moderate/severe disease.
• Numerous pre-treatment safety steps:
  • Confirm amyloid positivity (PET/CSF)
  • Rule out excessive microhemorrhages
  • Check APOE genotype due to massively higher ARIA risk in homozygotes (most centers treat this as a contraindication).
  • Screen for stroke, seizure, advanced comorbidities, active immunosuppressant therapy

  “If someone has more than four microhemorrhages... we are looking at the MRI to count the microhemorrhages, make sure there’s no aneurysm or other abnormality, where we would worry about risks.”
  —Dr. Halima Amjad (47:50)

• Therapy requires intense monitoring: frequent MRIs (especially early), and patient ability to tolerate infusions/injections.
• Benefits are real but modest: these therapies slow progression by ~25–30% (~5–7 months over 18 months) but do not halt or reverse disease. Many patients will still decline meaningfully.

  “It’s slowing cognitive and functional decline a little bit. The people receiving these drugs—they still experience decline over time.”
  —Dr. Halima Amjad (58:30)

• Deciding to initiate therapy requires careful discussion about risk, benefit, and patient goals.

4. Anti-Amyloid Drug Safety: ARIA & Other Adverse Effects

(51:55–58:30, 70:30–72:59)

• ARIA: Amyloid Related Imaging Abnormality (edema [ARIA-E] or microhemorrhage [ARIA-H]) is the leading risk; most cases asymptomatic, but can be severe or fatal, especially in APOE4 homozygotes.

  “Most ARIA is asymptomatic… only about 3–6% have symptoms. That’s why MRI monitoring is so important.”
  —Dr. Halima Amjad (52:24)

• Other adverse effects: headaches, infusion reactions. Any new neurological symptom warrants urgent MRI (not CT).
• Ongoing therapy adjustments are being developed as long-term data emerge, especially when patients complete initial 18 months of treatment.

5. The Big Picture: Evolving Practice and Controversies

(58:30–68:51)

• The amyloid theory is not the full answer; drugs remove amyloid, but clinical effects are mild.
• Controversy remains: “Are we just kicking the can down the road?” Are we prolonging early disease or also extending severe stages?
• Long-term management plans undecided for patients after initial therapy – maintenance regimens (infusion/subcutaneous), repeated scans, and the need for protocols still being developed.
• Primary care currently should not be the main site for ordering or interpreting blood-based Alzheimer’s biomarkers unless there is significant expertise; this will likely change as evidence and systems evolve.

Notable Quotes & Moments

• On Counseling & Patient Support:

  “People will forget what you said, people will forget what you did, but people will never forget how you made them feel. And I think when it comes to dementia care…that’s very true.”
  —Dr. Halima Amjad (05:28)

• On Functionality and Gray Zones:

  “...patients like this…sometimes they'll actually hear from one doctor that they have mild cognitive impairment, someone else will say they have dementia, and actually find myself kind of explaining to them why they might hear different things…”
  —Dr. Halima Amjad (14:36)

• On the State of the Field:

  “We’re living in pretty exciting times when it comes to dementia and Alzheimer’s…blood-based biomarkers…we have disease-modifying treatments…more attention and we’re seeing research translate to changes in clinical care…”
  —Dr. Halima Amjad (73:31)

Timestamps for Important Segments

• 06:41 – Case introduction & differentiating dementia/MCI
• 13:09 – Functional assessment: when is impairment “dementia”?
• 23:31 – Plasma biomarkers: indications, limitations, patient counseling
• 34:12 – What are these biomarkers, exactly? Types & interpretation
• 42:37 – Biomarker result: next steps, therapy considerations
• 45:14 – Pre-anti-amyloid therapy safety evaluation and eligibility
• 51:55 – ARIA: what is it, how common, who's at risk?
• 58:30 – Amyloid controversy: efficacy and theory challenges
• 64:39 – 18 months of therapy: now what?
• 73:31 – Take-home points from Dr. Amjad

Summary Take-Home Points

• Diagnosis of Alzheimer’s and appropriate use of new biomarkers require careful clinical context and a specialist’s input; blood tests are for symptomatic patients only.
• Anti-amyloid therapies are a significant advance but carry substantial risks, especially ARIA, and offer only modest slowing of decline in selected early-stage patients.
• Primary care should remain engaged but should seek specialist collaboration until protocols, experience, and evidence mature further. Stay tuned and up to date—this is a rapidly changing landscape.
• Patient/family counseling must set realistic expectations—these are not cures and involve complex safety monitoring.
• Research is ongoing: future directions may include preventive therapy and broader primary care involvement as practice evolves.

For further information and resources, see show notes and referenced guidelines.