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

TitleCognitive and Neuropsychological Profiles in Alzheimer's Disease and Primary Age-Related Tauopathy and the Influence of Comorbid Neuropathologies.
Publication TypeJournal Article
Year of Publication2023
AuthorsWalker, JM, Gonzales, MM, Goette, W, Farrell, K, Iii, CLWhite, Crary, JF, Richardson, TE
JournalJ Alzheimers Dis
Volume92
Issue3
Pagination1037-1049
Date Published2023
ISSN1875-8908
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Apolipoproteins E, Cognition, Executive Function, Humans, Tauopathies
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 ɛ4 alleles than the PART or NT cohort, and less frequent APOE ɛ2 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.

DOI10.3233/JAD-230022
Alternate JournalJ Alzheimers Dis
PubMed ID36847012
Grant ListP30 AG066512 / AG / NIA NIH HHS / United States
P30 AG066518 / AG / NIA NIH HHS / United States
P30 AG066507 / AG / NIA NIH HHS / United States
U24 AG072122 / AG / NIA NIH HHS / United States
P30 AG066511 / AG / NIA NIH HHS / United States
P20 AG068082 / AG / NIA NIH HHS / United States
P30 AG062677 / AG / NIA NIH HHS / United States
P30 AG062421 / AG / NIA NIH HHS / United States
P30 AG072975 / AG / NIA NIH HHS / United States
P30 AG072931 / AG / NIA NIH HHS / United States
P30 AG072980 / AG / NIA NIH HHS / United States
P30 AG072946 / AG / NIA NIH HHS / United States
P20 AG068024 / AG / NIA NIH HHS / United States
P30 AG072979 / AG / NIA NIH HHS / United States
P20 AG068077 / AG / NIA NIH HHS / United States
P30 AG072977 / AG / NIA NIH HHS / United States
P30 AG062429 / AG / NIA NIH HHS / United States
P30 AG066530 / AG / NIA NIH HHS / United States
P30 AG066444 / AG / NIA NIH HHS / United States
P30 AG066515 / AG / NIA NIH HHS / United States
P30 AG072978 / AG / NIA NIH HHS / United States
K01 AG070326 / AG / NIA NIH HHS / United States
P30 AG072976 / AG / NIA NIH HHS / United States
P30 AG066462 / AG / NIA NIH HHS / United States
P30 AG062422 / AG / NIA NIH HHS / United States
P30 AG066519 / AG / NIA NIH HHS / United States
P30 AG066468 / AG / NIA NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
P30 AG066508 / AG / NIA NIH HHS / United States
P30 AG072959 / AG / NIA NIH HHS / United States
P30 AG066514 / AG / NIA NIH HHS / United States
P30 AG072972 / AG / NIA NIH HHS / United States
P30 AG066546 / AG / NIA NIH HHS / United States
P30 AG072947 / AG / NIA NIH HHS / United States
P30 AG044271 / AG / NIA NIH HHS / United States
P30 AG066509 / AG / NIA NIH HHS / United States
P30 AG072958 / AG / NIA NIH HHS / United States
P30 AG066506 / AG / NIA NIH HHS / United States
P30 AG072973 / AG / NIA NIH HHS / United States
P20 AG068053 / AG / NIA NIH HHS / United States
P30 AG062715 / AG / NIA NIH HHS / United States
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