Forget Everything You Know About Alzheimer’s

Speaking Today

Michael J.

Koren,

MD, FACC, FAPCR, CPI

CEO, Jacksonville Center for Clinical Research

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Speaking Today

Ravi Pande, MD

Vascular and Interventional Neurologist

Dr. Ravi Pande is a Neuroendovascular surgeon who specializes in minimally invasive surgical treatment of complex cerebrovascular disorders such as strokes, aneurysms, brain and spinal cord AVM, vertebral stenosis, carotid stenosis, etc. He is a triple fellowship trained vascular and interventional neurologist. His areas of research interest include transradial and transcarotid Neurointerventions.

Forget Everything You Know About Alzheimer’s

Wednesday, July 19th, 2023

Ravi Pande, MD

Vascular and Interventional Neurologist

Michael J. Koren, MD, FACC, FAPCR, CPI

CEO, Jacksonville Center for Clinical Research

Dementia Definition

• Overall term for a particular group of symptoms

• Does not reference cause

• Refers to the severity of a cognitive deficit

• Characteristic symptoms of dementia: difficulties with memory, language, problemsolving and other thinking skills that affect a person's ability to perform everyday activities

https://www.alz.org/alzheimers-dementia/what-is-dementia

60-75% 15-20%

Dementia has Many Causes

• Alzheimer’s disease - most common cause of dementia (>50% cases).

• Vascular dementia - blood vessels in the brain are damaged and/or brain tissue is injured from not receiving enough blood, oxygen or nutrients.

• Lewy body disease - more likely to have initial or early symptoms of sleep disturbances, well-formed visual hallucinations and visuospatial impairment. Can occur with or without memory impairment.

• Fronto-temporal lobar degeneration (FTLD), Parkinson’s disease, Hippocampal sclerosis, and Mixed pathologies

True or False about Alzheimer’s Disease (AD)

A. Alzheimer’s Disease is a currently irreversible brain disorder that progressively degrades memory, cognitive function, and ability to carry out tasks of daily living.

B. Over 6 million Americans are believed to have AD.

C. AD is the sixth leading cause of death in the United States.

D. Pathophysiologic changes in the brain include amyloid plaques and neurofibrillary tangles of tau.

E. A and C only

F. All of the above

Initial Description

Patient: Auguste, D. – 51 years old, profound memory loss, unfounded suspicions about her family, and other worsening psychological incompetence. At autopsy, the brain demonstrated dramatic shrinkage and abnormal deposits in and around nerve cells. Described in 1906 by Dr. Alois Alzheimer.

Why Even Know About It?

Cases Projected to Double

Is it Alzheimer’s or Old Timers?

Is it Alzheimer’s or Old Timers?

Alzheimer’s Pathology

Protein fragment beta-amyloid (plaque) accumulation outside neurons in the brain

Twisted strands of the protein tau (tangles) inside neurons

Alzheimer’s Disease Risk Factors

Non-modifiable risk factors: Age, Family History, Genetics

Modifiable risk factors:

Obesity

Head trauma, high blood pressure, heart disease, stroke, diabetes, high cholesterol

Disease Modifying Approaches

• Focusing your attention on only one task at a time is the secret

• Live healthily

• Control blood pressure

• Sleep appropriately • Exercise

Diagnosis of Dementia due to Alzheimer’s Disease

Treatment of Alzheimer’s Dementia

Pharmacologic Treatment

 Rivastigmine, galantamine, donepezil – temporarily improve cognitive symptoms by increasing the amount of neurotransmitters in the brain; provide only modest symptomatic benefit and do not attenuate the course of the disease

 Memantine – blocks certain receptors in the brain from excess stimulation that can damage nerve cells

 Aducanumab (Aduhelm) – helps the immune system break down and remove beta-amyloid plaques to (theoretically) slow down damage to the nerve cells

History of Vascular Dementia

“I have observed in many cases that when, the brain being indisposed, they have been distempered with a dullness of mind and forgetfulness, and then afterward with a stupidity and foolishness, they would afterward have fallen into a Palsie, which I oft did predict…,” wrote Thomas Willis in 1672.

Dr. Alois Alzheimer

• Believed that there were three main types of Dementia

• Syphilitic/GPI (known since 1822)

• Arteriosklerotische atrophie (1894)

• Senile (AD)

Epidemiology (21st century)

• VD is the 2nd most common cause of dementia

• VD accounts for roughly 15% to 20% of dementia cases in North America and Europe

• Many patients with VD also have AD or LBD pathology (Mixed Dementia)

• Similar to AD, the incidence of vascular dementia increases steeply with age, contributing to the growing epidemic of dementia in the aging populations worldwide

Overlap between AD and VD

• VD and AD share risk factors

• VD and AD have overlapping neuropathology

• VD increases the risk of AD

• VD promotes speed of progression of AD

What causes Vascular Dementia

• Acute stroke due to strategic damage in memory center

• Post stroke Dementia, moderate to large territorial stroke

• Multi infarct Dementia

• Subcortical Small vessel disease or lacunar strokes (subcortical gray and white matter)

• Binswanger’s Disease (extensive demyelination associated with arteriolosclerosis of deep white-matter vessels)

• Intracranial hemorrhage or series of small/microhemorrhages

• Amyloid angiopathy

• CADASIL

Rosenberg GA, Wallin A, Wardlaw JM, et al. Consensus statement for diagnosis of subcortical small vessel disease. Journal of Cerebral Blood Flow & Metabolism. 2016;36(1):6-25.

Typical Presentation of VD

• Changes in thinking skills usually occur suddenly after a stroke (within 3 months post stroke)

• Thinking difficulties may also begin as mild changes that gradually worsen as a result of multiple minor strokes or another condition that affects smaller blood vessels, leading to widespread damage.

• Typical domains affected

• Memory, language, other cognitive domains

https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/vascular-dementia

Symptoms

• Confusion

• Disorientation

• Trouble speaking or understanding speech

• Difficulty walking

• Poor balance

• Numbness or paralysis on one side of the face or the body

• Impaired planning and judgment, uncontrolled laughing and crying, declining ability to pay attention, impaired functionality in social situations, and difficulty finding the right words

Diagnosis per AAN guidelines

1. Confirmed by neurocognitive testing (hours of written or computerized tests that provide detailed evaluation of specific thinking skills such as judgment, planning, problem-solving, reasoning, and memory)

2. MRI confirming recent stroke or other vascular brain changesseverity and pattern of affected tissue are consistent with the types of impairment documented in cognitive testing

3. No evidence that nonvascular factors may contribute to cognitive decline

How to prevent VD

Goal: reduce the risk of developing diseases that affect the heart and blood vessels — and help protect the brain:

• Don't smoke

• Keep your blood pressure, cholesterol and blood sugar within recommended limits

• Eat a healthy, balanced diet

• Exercise

• Maintain a healthy weight

• Limit alcohol consumption

https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/vascular-dementia

Treatment

• The U.S. Food and Drug Administration (FDA) has not approved any drugs specifically to treat symptoms of vascular dementia

• Controlling risk factors that may increase the likelihood of further damage to the brain’s blood vessels is an important treatment strategy

• Substantial evidence that treatment of risk factors may improve outcomes and help postpone or prevent further decline.

Treatment (continued)

Non-pharmacologic therapies – goal to improve cognitive function and perform ADLs

 Aerobic exercise

 Cognitive stimulation and cognitive training

 Listening to favorite music to stir recall

 Using special lighting to lessen sleep disorders

Aducanumab (Aduhelm) –Biogen

 Monoclonal antibody - first drug on the market able to clear away amyloid plaques

 FDA approved on June 7, 2021 despite evidence did not meet primary outcome of slowing cognitive decline

 January 11, 2022 CMS stated Medicare would pay for the drug only for subjects in randomized clinical trials.

FDA Accelerated Approval for Lecanemab (Leqembi)

• 1795 patients enrolled

• Statistically significant reduction in brain amyloid plaque

• Acknowledged need for real-world evidence and longterm safety data collection

Clinical Trial Shows Promise for Donanemab

• 1700 patients enrolled

• Slowed progression of Alzheimer’s by ~35%

• Monoclonal antibody designed to remove amyloid plaque from the brain

Clinical Research Studies

Participating in clinical trials can help both the individual participant and other individuals who have Alzheimer’s or are at risk of developing it.

• You can play a more active role in your own health care

• You can gain access to potential treatments before they are widely available

• You can receive expert medical care at no cost to you while participating in important medical research

• You can help future generations – your children and grandchildren- by contributing to Alzheimer’s research

QUESTIONS?