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January 13, 2021Article

Memory resilience in Alzheimer's disease with primary progressive aphasia

M.-Marsel Mesulam, View ORCID ProfileChristina Coventry, Alan Kuang, Eileen H. Bigio, Qinwen Mao, Margaret E. Flanagan, Tamar Gefen, Jaiashre Sridhar, Changiz Geula, Hui Zhang, Sandra Weintraub, Emily J. Rogalski
First published January 13, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011397
M.-Marsel Mesulam
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
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Christina Coventry
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
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  • ORCID record for Christina Coventry
Alan Kuang
2Department of Preventive Medicine, Northwestern University Feinberg School of Medicine.
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Eileen H. Bigio
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
3Department of Pathology, Northwestern University Feinberg School of Medicine.
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Qinwen Mao
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
3Department of Pathology, Northwestern University Feinberg School of Medicine.
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Margaret E. Flanagan
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
3Department of Pathology, Northwestern University Feinberg School of Medicine.
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Tamar Gefen
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
4Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine.
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Jaiashre Sridhar
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
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Changiz Geula
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
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Hui Zhang
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
2Department of Preventive Medicine, Northwestern University Feinberg School of Medicine.
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Sandra Weintraub
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
4Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine.
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Emily J. Rogalski
1Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine.
4Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine.
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Citation
Memory resilience in Alzheimer's disease with primary progressive aphasia
M.-Marsel Mesulam, Christina Coventry, Alan Kuang, Eileen H. Bigio, Qinwen Mao, Margaret E. Flanagan, Tamar Gefen, Jaiashre Sridhar, Changiz Geula, Hui Zhang, Sandra Weintraub, Emily J. Rogalski
Neurology Jan 2021, 10.1212/WNL.0000000000011397; DOI: 10.1212/WNL.0000000000011397

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Abstract

Objective To determine whether memory is preserved longitudinally in primary progressive aphasia (PPA) associated with Alzheimer's disease (AD), and to identify potential factors that maintain memory despite underlying neurofibrillary degeneration of mediotemporal memory areas.

Methods Longitudinal memory assessment in 17 PPA patients with autopsy or biomarker evidence of AD (PPA-AD) and 14 patients with amnestic dementia of the Alzheimer type with AD at autopsy (DAT-AD).

Results In PPA-AD, episodic memory, tested with nonverbal items, was preserved at initial testing and showed no decline at retesting 2.35 ± 0.78 years later, at which time symptoms had been present for 6.26 ± 2.21 years. In contrast, language functions declined significantly during the same period. In DAT-AD, both verbal memory and language declined with equal severity. Although imaging showed asymmetric left sided mediotemporal atrophy in PPA-AD, autopsy revealed bilateral hippocampo-entorhinal neurofibrillary degeneration at Braak stages V and VI. In comparison to DAT-AD, however, the PPA-AD group had lower incidence of Apolipoprotein E4 and of mediotemporal TDP-43 pathology.

Conclusions Memory preservation in PPA is not just an incidental finding at onset but a core feature that persists for years despite the hippocampo-entorhinal AD neuropathology that is as severe as that of DAT-AD. Asymmetry of mediotemporal atrophy and a lesser impact of Apolipoprotein E4 and of TDP-43 on the integrity of memory circuitry may constitute some of the factors underlying this resilience. Our results also suggest that current controversies on memory in PPA-AD reflect inconsistencies in the diagnosis of logopenic PPA, the clinical variant most frequently associated with AD.

  • Received July 1, 2020.
  • Accepted in final form September 25, 2020.
  • © 2021 American Academy of Neurology

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  • Memory
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  • Cognitive neuropsychology in dementia

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