Factors that predict diagnostic stability in neurodegenerative dementia

  • David C. PerryEmail author
  • Samir Datta
  • Zachary A. Miller
  • Katherine P. Rankin
  • Maria Luisa Gorno-Tempini
  • Joel H. Kramer
  • Howard J. Rosen
  • William W. Seeley
  • Bruce L. Miller
Original Communication



To determine the frequency and characteristics of clinical diagnostic change in frontotemporal dementia (FTD)-spectrum syndromes and Alzheimer’s disease (AD)-type dementia.


We reviewed records and categorized diagnostic changes in patients seen ≥ 2 times with behavioral variant FTD (bvFTD, n = 99), nonfluent and semantic variant primary progressive aphasia (nfvPPA, n = 32; svPPA, n = 59), corticobasal syndrome (CBS, n = 40), progressive supranuclear palsy-Richardson syndrome (PSP-RS, n = 34), and AD-type dementia (n = 49). For bvFTD, we compared patients with and without diagnostic change, and assessed predictors of diagnostic change by logistic regression.


Initial diagnoses changed infrequently at subsequent visits in svPPA (6.8%), PSP-RS (8.8%), and nfvPPA (12.5%), with rare changes largely involving clinicopathological overlap or diagnostic ambiguity. Changes in AD-type dementia (30.6%) and CBS (37.5%) were more common, but reflected greater specificity, predicted co-pathology, or overlapping syndromes. Diagnostic change in bvFTD was also common (32.3%), but more diverse, including motor neuron disease development, alternative neurodegenerative syndromes, and non-neurodegenerative diseases. Diagnostic change occurred more often in those who met possible rather than probable bvFTD criteria (70.6% vs 15.3%, p < 0.001). Patients with stable diagnoses showed greater overall impairment, bvFTD behavioral severity, and atrophy in core right-hemisphere bvFTD regions. Patients with diagnostic change had more severe depression (p < 0.05) and more frequent contributing, secondary diagnoses (p = 0.01), such as cerebrovascular disease. By logistic regression, the accuracy of predicting stable bvFTD diagnoses using first-visit data was 80%.


bvFTD displays more diverse diagnostic change than other neurodegenerative syndromes. First-visit bvFTD diagnoses may waver if based on meeting possible criteria only.


Frontotemporal dementia Corticobasal degeneration Progressive supranuclear palsy Alzheimer’s disease 



This study was supported by Grants K23AG045289 (DCP) and P01AG019724 (BLM) from the NIH. Dr. Perry, Mr. Datta, Dr. ZA Miller, Dr. Rankin, Dr. Gorno-Tempini, Dr. Kramer, Dr. Rosen, and Dr. BL Miller report no relevant disclosures. Dr. Seeley reports receiving consulting fees from Biogen Idec, Third Rock Ventures, Merck, Inc., and Bristol-Myers Squibb.

Compliance with ethical standards

Conflicts of interest

The authors report no conflicts of interest.

Ethical approval

This study was approved by the UCSF Committee on Human Research.

Informed consent

Written informed consent was obtained from patients or surrogates, in accordance with the Declaration of Helsinki.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • David C. Perry
    • 1
    Email author
  • Samir Datta
    • 1
  • Zachary A. Miller
    • 1
  • Katherine P. Rankin
    • 1
  • Maria Luisa Gorno-Tempini
    • 1
  • Joel H. Kramer
    • 1
  • Howard J. Rosen
    • 1
  • William W. Seeley
    • 1
  • Bruce L. Miller
    • 1
  1. 1.Department of Neurology, Memory and Aging Center, UCSF Weill Institute for NeurosciencesUniversity of California, San FranciscoSan FranciscoUSA

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