Hippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy

Gregory A. Jicha, MD, PhD; Peter T. Nelson, MD, PhD Dementia p. 208-233 February 2019, Vol.25, No.1 doi: 10.1212/CON.0000000000000697
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PURPOSE OF REVIEW: Hippocampal sclerosis, argyrophilic grain disease, and primary age-related tauopathy are common Alzheimer disease mimics that currently lack clinical diagnostic criteria. Increased understanding of these pathologic entities is important for the neurologist who may encounter patients with an unusually slowly progressive degenerative dementia that may appear to meet criteria for Alzheimer disease but who progress to develop symptoms that are unusual for classic Alzheimer disease

RECENT FINDINGS: Hippocampal sclerosis has traditionally been associated with hypoxic/ischemic injury and poorly controlled epilepsy, but it is now recognized that hippocampal sclerosis may also be associated with a unique degenerative disease of aging or may be an associated pathologic finding in many cases of frontotemporal lobar degeneration. Argyrophilic grain disease has been recognized as an enigma in the field of pathology for over 30 years, but recent discoveries suggest that it may overlap with other tau-related disorders within the spectrum of frontotemporal lobar degeneration. Primary age-related tauopathy has long been recognized as a distinct clinical entity that lies on the Alzheimer pathologic spectrum, with the presence of neurofibrillary tangles that lack the coexistent Alzheimer plaque development; thus, it is thought to represent a distinct pathologic entity.

SUMMARY: Despite advances in dementia diagnosis that suggest that we have identified and unlocked the mysteries of the major degenerative disease states responsible for cognitive decline and dementia in the elderly, diseases such as hippocampal sclerosis, argyrophilic grain disease, and primary age-related tauopathy demonstrate that we remain on the frontier of discovery and that our diagnostic repertoire of diseases responsible for such clinical symptoms remains in its infancy. Understanding such diagnostic confounds is important for the neurologist in assigning appropriate diagnoses and selecting appropriate therapeutic management strategies for patients with mild cognitive impairment and dementia.

Address correspondence to Dr Gregory A, Jicha, Sanders-Brown Center on Aging, 1030 S Broadway, Ste #5, Lexington, KY 40504, gregory.jicha@uky.edu.

RELATIONSHIP DISCLOSURE: Dr Jicha serves as a consultant for the Cure Alzheimer’s Fund and provides contract research for AbbVie Inc; Alltech; Axovant Sciences, Inc; Eli Lilly and Company; Eisai Inc; Janssen Global Services, LLC; Novartis AG; Suven Life Sciences Limited; and VTV Therapeutics. Dr Jicha receives research/grant support from the National Institutes of Health (UH2 NS100606, R01 AG054130, U19 AG010483, U24 AG057437, P30 AG028383, R01 HD064993, R01 AG057187, R01 AG042419, R01 NR014189). Dr Nelson serves on the National Institutes of Health/National Institute on Aging external advisory boards of Mayo Clinic and Rush University and as an associate editor for Acta Neuropathologica and the Journal of Neuropathology & Experimental Neurology.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Jicha and Nelson report no disclosures.

© 2019 American Academy of Neurology