Late-onset Alzheimer Disease

Gil D. Rabinovici, MD p. 14-33 February 2019, Vol.25, No.1 doi: 10.1212/CON.0000000000000700
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PURPOSE OF REVIEW: Alzheimer disease (AD) is the most common cause of late-onset dementia. This article describes the epidemiology, genetic and environmental risk factors, clinical diagnosis, biomarkers, and treatment of late-onset AD, defined by age of onset of 65 years or older.

RECENT FINDINGS: An estimated 5.7 million Americans are living with AD dementia, with the number of affected individuals growing rapidly because of an aging population. Vascular risk factors, sleep disorders, and traumatic brain injury are associated with an increased risk of AD, while increased cognitive and physical activity throughout the lifespan reduce the risk of disease. The primary genetic risk factor for late-onset AD is the apolipoprotein E (APOE) ε4 allele. AD typically presents with early and prominent episodic memory loss, although this clinical syndrome is neither sensitive nor specific for underlying AD neuropathology. Emerging CSF and imaging biomarkers can now detect the key neuropathologic features of the disease (amyloid plaques, neurofibrillary tangles, and neurodegeneration) in living people, allowing for characterization of patients based on biological measures. A comprehensive treatment plan for AD includes use of symptomatic medications, optimal treatment of comorbid conditions and neuropsychiatric symptoms, counseling about safety and future planning, and referrals to community resources.

SUMMARY: AD is very common in older neurologic patients. Neurologists should set the standard for the diagnosis and care of patients with AD and should be familiar with emerging biomarkers that have transformed AD research and are primed to enter the clinical arena.

Address correspondence to Dr Gil D. Rabinovici, University of California San Francisco Memory and Aging Center, 675 Nelson Rising Ln, Ste 190, San Francisco, CA 94158,

RELATIONSHIP DISCLOSURE: Dr Rabinovici receives research/grant support from the National Institutes of Health (P01-AG019724, P50-AG23501, R01 AG032289, R01-AG045611, R01-AG048234, R01 AG057204, R56-AG057195) and the National Institute of Neurological Disorders and Stroke (R01-AG038791). Dr Rabinovici receives research support from Avid Radiopharmaceuticals, Eli Lilly and Company, General Electric Healthcare, and Life Molecular Imaging. Dr Rabinovici has served on scientific advisory boards for AXON Neuroscience SE; Eisai Co, Ltd; F. Hoffman-La Roche Ltd; Genentech, Inc; and Merck & Co, Inc. Dr Rabinovici serves as an associate editor for JAMA Neurology.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Rabinovici discusses the investigational use of the positron emission tomography (PET) radiotracers [11C]Pittsburgh Compound B and [18F]flortaucipir in the diagnosis of Alzheimer disease.

© 2019 American Academy of Neurology.