Course Title: Plenary B - The Neuropsychological Syndrome of Primary Progressive Aphasia (PPA) as a Dementia Syndrome (Weintraub)

Credit Hours: 1

Instructor(s) Sandra Weintraub

Sandra Weintraub, PhD
Professor of Psychiatry and Behavioral Sciences (Psychology) and Neurology
Feinberg School of Medicine
Northwestern University

Plenary B:

The Neuropsychological Syndrome of Primary Progressive Aphasia (PPA) as a Dementia Syndrome

Abstract & Learning Objectives:

Primary Progressive Aphasia (PPA) was first named “Slowly Progressive Aphasia” and described as an atypical clinical presentation of dementia in 1982. In the years that followed, there was controversy about its legitimacy as a distinct “disease” and some argued that it was a “variant” of Alzheimer’s disease. This controversy blossomed into years of research that revealed PPA as a clinical dementia syndrome, characterized by early aphasia that can persist in isolation for many years and that can be caused by a variety of neurodegenerative brain diseases, including Alzheimer’s disease (AD) and one of the several forms of frontotemporal lobar degeneration (e,g, tauopathies, TDP-43 proteinopathy), albeit in distinct probabilities. The single unifying theme in PPA, as would be predicted by neuropsychological principles, is that the patients with the syndrome have an neuroanatomical vulnerability of the left cerebral hemisphere language areas, to neurodegenerative disease. Successive post mortem studies of the brains of individuals with PPA revealed asymmetric left hemisphere distribution of neuropathologic change, regardless of the disease. Thus, Alzheimer’s plaques and tangles, TDP-43 inclusions and Pick’s disease tauopathy have all been observed in higher frequency in the left that in the right cerebral hemisphere at post mortem. Even when disease spreads to the right hemisphere, the asymmetry can persist for many years to death. Even when PPA is caused by AD neuropathology, the ApoE E4 allele, the best know genetic risk factor for AD, is not as highly represented in the clinical syndrome of PPA as in the clinical syndrome of amnestic dementia with AD, suggesting that AD itself is not a unitary disease. Recently, we have proposed that individual risk for PPA, regardless of the cause, might be linked to intrinsic left hemisphere vulnerability to disease. In some members of families we have studied, there is a strong history of developmental dyslexia while in others, PPA emerges in late life, both conditions reflecting left hemisphere biological vulnerability. The neuropsychological evaluation of an individual with PPA is challenging because many of our test instruments rely on normal verbal communication skills. We have developed some clinical tests to circumvent the aphasia in assessing retentive memory and reasoning. The nosology of dementia, previously considered a neuroanatomically diffuse and cognitively widespread condition, has been transformed by the study of PPA. We now recognize the principle of anatomical specificity of neurodegenerative diseases of the brain that cause dementia, that result in highly focal neuropsychological profiles, especially in early years of illness. Because aphasia is different from amnesia in its impact on daily life, we have also designed specialized care pathways for patients with PPA and their caregivers tailored to their distinct needs

Upon conclusion of this course, learners will be able to:

  • Describe the most up-to-date criteria for the clinical diagnosis of primary progressive aphasia (PPA) and how it is differentiated from other clinical dementia syndromes in the early stages
  • List developmental risk factors that might underlie early cortical vulnerability to the PPA syndrome as opposed to other dementia syndromes that feature episodic memory loss
  • Explain neuropsychological tests to clinically distinguish PPA from other dementia syndromes as well as interventions for treatment of patients with PPA and their caregivers

Speaker Biography:

Dr. Sandra Weintraub is Professor of Psychiatry and Behavioral Sciences (Psychology) and Neurology at Feinberg School of Medicine at Northwestern University. Her focus is Alzheimer's disease, Memory disorders, Neuropsychology, Early Onset Dementia, Primary Progressive Aphasia, Frontotemporal Dementia, and Superaging. The ability to use language can be progressively disrupted by neurodegenerative diseases of the brain that target circumscribed regions that normally mediate language in healthy individuals. Dr. Weintraub's clinical and research interests focus on Individuals with Primary Progressive Aphasia, Frontotemporal Dementia and Alzheimer's Disease. Research projects address the neuropsychological, neuroimaging and neuropathological variables associated with these syndromes, in order to contribute to our understanding of risk and the genetic factors that determine regional brain vulnerability to these diseases and to identify biomarkers that can be used in diagnosis during the patient's lifetime. To date, there are no biomarkers that definitively predict the type of the neuropathology in these clinical syndromes in the individual patient. Additional interests in the area of brain aging and its effects on cognition lie in determining factors associated with "Superaging", the maintenance of a high level of cognitive ability into the 9th decade of life and beyond.