Acknowledgement of Commercial Support
This activity is supported by an educational grant from Biogen and Lilly. For further information concerning Lilly grant funding visit www.lillygrantoffice.com.
This activity is provided by Physicians’ Education Resource®, LLC.
Dates of Certification:
December 28, 2017-December 28, 2018
Richard S. Isaacson, MD
Director of the Alzheimer’s Prevention Clinic
Weill Cornell Memory Disorders Program
Director of the Neurology Residency Training Program
Weill Cornell Medical College/New York-Presbyterian Hospital
New York, New York
Disclosure: Consultant: 23 and Me, Eli, Lilly, Neurotrack
Howard Fillit, MD
Founding Executive Director and Chief Science Officer
Alzheimer’s Drug Discovery Foundation
Clinical Professor of Geriatric Medicine and Neuroscience
The Icahn School of Medicine at Mount Sinai
New York, New York
Disclosure: Consultant: Axovant Sciences, Eli Lilly, Merck & Co., Otsuka
Disclosure: No relevant financial relationships with commercial interests
Disclosure: No relevant financial relationships with commercial interests
Despite the substantial progress made in understanding and treating Alzheimer’s disease in recent years, no disease modifying treatments are available such that care is limited to treatment of dementia symptoms and pursuit of the best possible quality of life. During this Medical Crossfire®, expert faculty will engage in a multidisciplinary roundtable discussion that includes a neurologist and a geriatrician. A patient advocate and early-stage patient give voice to the many facets of lifestyle management and future planning. This activity provides key guidance for diagnosing and treating Alzheimer’s disease and promoting the collaborative care between primary care providers, geriatricians, neurologists and psychiatrists who not only have the patients’ needs at heart, but include caregivers as a member of the multidisciplinary team, steadfastly involved in decision-making processes.
This activity is directed to primary care providers, neurologists, geriatric specialists, and psychiatrists who treat patients with Alzheimer’s Disease. Nurse practitioners, nurses, physician assistants, researchers, and other healthcare professionals interested in the treatment of Alzheimer’s disease are invited to participate.
At the completion of this activity, you should be better prepared to:
Describe neurodegenerative changes that are considered the hallmarks of Alzheimer’s disease (AD)
Describe screening and diagnostic tools for the early identification of individuals with AD
Describe emerging biomarkers for earlier and more accurate diagnosis
Select appropriate therapy for patients with AD to slow disease progression and improve patient and caregiver quality of life (QoL)
Describe lifestyle modifications that can improve QoL for patients and caregivers
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Recap 1 of 3: Pathophysiology of Alzheimer’s Disease
Alzheimer’s disease (AD) is a chronic, progressive, uniformly fatal neurodegenerative disease of the human mind. It has a typical progression, although each patient’s trajectory is unique.1
It is the leading cause of disability in people older than 75 years.1
According to geriatrician and neuroscientist Howard Fillit, MD, physicians should “have a high index of suspicion in the real population at risk, which is usually people over the age of 75, and use the most efficient appropriate instrument available to you to screen.” People who develop AD often notice that their memory seems to be failing, a situation called subjective memory impairment. They may progress to mild cognitive decline, which is characterized by mild memory changes, forgetfulness, and sometimes problems with executive function (eg, judgment, orientation, reasoning, planning).2
Mild cognitive impairment can be mildly disabling, but usually impairs function only marginally.1
Not all patients who have mild cognitive impairment progress to AD, but about 44% do.3
AD then progresses to mild dementia, where affected individuals have impairments in at least 2 domains of cognitive function. In 90% of affected individuals, for example, memory loss or amnesia is a prominent feature. Patients experience challenges with abstract reasoning and planning, and often become apathetic. The disease begins to impair activities of daily living and functioning. Patients may also experience language and comprehension problems. At this point, people with AD begin to need assistance with shopping, cleaning, and paying bills.1
As the disease moves into the mild to moderate stages, patients need considerably more assistance. Cognitive deficits become severe, and independent function progresses toward complete dependence on others. In the severe stage, patients are bedridden.1
In terms of pathophysiology, AD has been associated with several different physiologic changes. Among them are the following4-8
Extraneuronal toxic amyloid oligomers and proteins
Intraneuronal neurofibrillary tangles consisting of hyperphosphorylated tau
Region-specific diminished cerebral glucose metabolism
The earliest and most robust research has been related to the APO E4 gene. Patients who have 1 gene are at 4 times the risk of people lacking this gene, and those who have 2 APO E4 genes have a 10 times greater risk.9
Accumulation of extracellular amyloid plaques or intracellular oligomers are thought to be essential to AD development. Although its mechanism of action is not completely clear, amyloid is thought to lead to AD via increased oxidative stress, mitochondrial dysfunction, synaptic disruption, and hyperphosphorylation of tau. Tau is a microtubule-associated protein that facilitates intracellular signaling processes, and hyperphosphorylated tau leads to microtubule dissociation in neurons, compromising axonal transport and diminishing synaptic function.
It appears that AD begins in the fifth or sixth decade of life. It can be detected on a positron emission tomography (PET) scan as amyloid or on a spinal tap in which the laboratory measures amyloid beta 42 and 40 and/or phosphorylated tau. Individuals who have positive results on this test have about a 50% chance of developing dementia within 3 to 5 years.10
A skilled clinician needs to recognize that patients may have more than 1 type of dementia or possibly comorbid delirium.
Individuals who are developing AD may or may not report subjective memory impairment; many patients are skilled at hiding their memory loss
Approximately 44% of patients who develop mild cognitive impairment will progress to AD
Watch for changes in abstract reasoning, planning, and apathy as signs that dementia may be developing
Patients who have 1 APO E4 gene have 4 times the risk of developing AD; those with 2 APO E4 genes have 10 times the risk
Patients with positive results on amyloid beta 42 and 40 tests have a 50% chance of developing dementia within 3 to 5 years
1. Oboudiyat C, Glazer H, Seifan A, Greer C, Isaacson RS. Alzheimer’s disease. Semin Neurol
. 2013;33(4):313-329. doi: 10.1055/s-0033-1359319.
2. Valech N, Tort-Merino A, Coll-Padrós N, et al. Executive and language subjective cognitive decline complaints discriminate preclinical Alzheimer’s disease from normal aging. J Alzheimers Dis
. 2018;61(2):689-703. doi: 10.3233/JAD-170627.
3. Emory University Alzheimer’s Disease Research Center. What is mild cognitive impairment? alzheimers.emory.edu/healthy_aging/mild-cognitive-impairment/index.html. Accessed January 23, 2018.
4. Bateman RJ, Aisen PS, De Strooper B, et al. Autosomal-dominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease. Alzheimers Res Ther
. 2011;3(1):1. doi: 10.1186/alzrt59.
5. Ittner LM, Götz J. Amyloid-β and tau—a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci
. 2011;12(2):65-72. doi: 10.1038/nrn2967.
6. Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci
. 2007;8(9):663-672. doi: 10.1038/nrn2194.
7. Silva DF, Selfridge JE, Lu J, Lezi E, Cardoso SM, Swerdlow RH. Mitochondrial abnormalities in Alzheimer’s disease: possible targets for therapeutic intervention. Adv Pharmacol
. 2012;64:83-126. doi: 10.1016/B978-0-12-394816-8.00003-9.
8. Supnet C, Bezprozvanny I. The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium
. 2010;47(2):183-189. doi: 10.1016/j.ceca.2009.12.014.