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Distinct contributions of longitudinal tau and amyloid to decline in various cognitive domains in preclinical AD
Author(s) -
Farrell Michelle E.,
Papp Kathryn V.,
Jacobs Heidi I.L.,
Buckley Rachel F.,
Properzi Michael J.,
Schultz Aaron P.,
Hanseeuw Bernard,
Rentz Dorene M.,
Johnson Keith A.,
Sperling Reisa A.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046075
Subject(s) - cognitive decline , psychology , cognition , pittsburgh compound b , longitudinal study , mediation , neuroscience , medicine , dementia , disease , cognitive impairment , pathology , political science , law
Background We sought to assess the preclinical contributions of longitudinal Aβ and tau accumulation at different baseline Aβ levels to decline across multiple cognitive domains. Method 124 clinically normal older adults from the Harvard Aging Brain Study with longitudinal Aβ (PIB), tau (FTP) and cognition (PACC) were included (median follow‐up=8.0±1.0 years). The following linear mixed models examined neocortical PIB and inferior temporal (IT) FTP change effects on PACC and its component tasks and included age, sex, APOE and education as covariates: 1) Time*PIB level t 0 *PIB change t 0‐3 on cognition t 0‐8, with post‐hoc regional analyses. 2) Time*PIB level t 3 *FTP change t 3‐8 on cognition t 3‐8 , because FTP was introduced at t 3. Mediation analyses assessed whether the effect of PIB change t 0‐3 on subsequent cognitive decline t 3‐8 was mediated by IT‐FTP at t 3.Result Increasing PIB change‐t 0‐3 was associated with declining cognition‐t 0‐8 across all tasks at higher PIB‐t 0 levels (Figure 1). The Digit Symbol Substitution Test (DSST) also declined with increasing PIB change at low PIB‐t 0 levels ( β= ‐1.99, p =.002). FTP change‐t 3‐5 was associated with declines at high PIB‐t 3 levels for all PACC components except DSST (Figure 2). Only free recall (Free and Cued Selective Reminding Test; FCsrt‐FR) exhibited FTP change‐related decline in low PIB adults ( β =‐1.70, p =.02). Mediation analyses demonstrated that FTP‐t 3 mediated the effect of PIB change t 0‐3 on cognitive decline t 3‐8 for all PACC components except DSST, which remained associated only with PIB change (Figure 3). Regional analyses revealed different patterns of increasing PIB change associated with FCsrt‐FR and DSST decline (Figure 4). Conclusion Two different patterns of cognitive decline were observed: 1) A tau‐mediated pattern of steeper decline across multiple domains in individuals with high Aβ. Free recall declined starting at low Aβ levels, in association with tau and accumulating Aβ in regions important for memory retrieval. 2) A decline on the DSST associated with accumulating Aβ, but not IT tau, even in those with low Aβ. DSST involves processing speed and executive function. The broader pattern of Aβ accumulation was associated with DSST decline suggests it may reflect a general cognitive slowing in response to Aβ‐mediated changes in synaptic transmission.