Cognitive and Neuropsychological Profiles in Alzheimer's Disease and Primary Age-Related Tauopathy and the Influence of Comorbid Neuropathologies

Jamie M. Walker, Mitzi M. Gonzales, William Goette, Kurt Farrell, Charles L. White, John F. Crary, Timothy E. Richardson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Alzheimer's disease neuropathologic change (ADNC) is defined by the progression of both hyperphosphorylated-tau (p-tau) and amyloid-β (Aβ) and is the most common underlying cause of dementia worldwide. Primary age-related tauopathy (PART), an Aβ-negative tauopathy largely confined to the medial temporal lobe, is increasingly being recognized as an entity separate from ADNC with diverging clinical, genetic, neuroanatomic, and radiologic profiles. Objective: The specific clinical correlates of PART are largely unknown; we aimed to identify cognitive and neuropsychological differences between PART, ADNC, and subjects with no tauopathy (NT). Methods: We compared 2,884 subjects with autopsy-confirmed intermediate-high stage ADNC to 208 subjects with definite PART (Braak stage I-IV, Thal phase 0, CERAD NP score 'absent') and 178 NT subjects from the National Alzheimer's Coordinating Center dataset. Results: PART subjects were older than either ADNC or NT patients. The ADNC cohort had more frequent neuropathological comorbidities as well as APOE ϵ4 alleles than the PART or NT cohort, and less frequent APOE ϵ2 alleles than either group. Clinically, ADNC patients performed significantly worse than NT or PART subjects across cognitive measures, but PART subjects had selective deficits in measures of processing speed, executive function, and visuospatial function, although additional cognitive measures were further impaired in the presence of neuropathologic comorbidities. In isolated cases of PART with Braak stage III-IV, there are additional deficits in measures of language. Conclusion: Overall, these findings demonstrate underlying cognitive features specifically associated with PART, and reinforce the concept that PART is a distinct entity from ADNC.

Original languageEnglish (US)
Pages (from-to)1037-1049
Number of pages13
JournalJournal of Alzheimer's Disease
Volume92
Issue number3
DOIs
StatePublished - 2023

Keywords

  • Alzheimer's disease
  • Clinical Dementia Rating
  • Lewy body dementia
  • Mini-Mental State Examination
  • cerebrovascular disease
  • limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC)
  • primary age-related tauopathy

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Clinical Psychology
  • General Neuroscience

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