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. 2022 Jan 31:13:806432.
doi: 10.3389/fnagi.2021.806432. eCollection 2021.

Longitudinal Trajectories of Participant- and Study Partner-Rated Cognitive Decline, in Relation to Alzheimer's Disease Biomarkers and Mood Symptoms

Catherine E Munro  1 , Rachel Buckley  2   3   4 , Patrizia Vannini  1   5 , Carla DeMuro  6 , Reisa Sperling  3   5 , Dorene M Rentz  2   3 , Keith Johnson  3   7 , Jennifer R Gatchel  2   8 , Rebecca Amariglio  1
Affiliations

Longitudinal Trajectories of Participant- and Study Partner-Rated Cognitive Decline, in Relation to Alzheimer's Disease Biomarkers and Mood Symptoms

Catherine E Munro et al. Front Aging Neurosci. .

Abstract

Whereas discrepancies between participant- and study partner-reported cognitive concerns on the Alzheimer's disease (AD) continuum have been observed, more needs to be known regarding the longitudinal trajectories of participant- vs. study partner-reported concerns, particularly their relationship to AD biomarkers and mood symptomology. Additionally, it is unclear whether years of in-clinic data collection are needed to observe relationships with AD biomarkers, or whether more frequent, remote assessments over shorter periods of time would suffice. This study primarily sought to examine the relationships between longitudinal trajectories of participant- and study partner-rated cognitive decline and baseline biomarker levels [i.e., amyloid and tau positron emission tomography (PET)], in addition to how mood symptomatology may alter these trajectories of concerns over a 2-year period. Baseline mood was associated with longitudinal participant-rated concerns, such that participants with elevated depression and anxiety scores at baseline had decreasing concerns about cognitive decline over time (fixed estimate = -0.17, 95% CI [-0.29 to -0.05], t = -2.75, df = 457, adj. p = 0.012). A significant interaction between baseline amyloid (fixed estimate = 4.07, 95% CI [1.13-7.01], t = 2.72, df = 353, adj. p = 0.026) and tau (fixed estimate = 3.50, 95% CI [0.95-6.06], t = 2.70, df = 331, adj. p = 0.030) levels was associated with increasing study partner concerns, but not participant concerns, over time. The interaction between amyloid and study partner concerns remained significant when utilizing only the first year of concern-related data collection. Overall, these results suggest that frequent, remote assessment of study partner-reported concerns may offer additional insight into the AD clinical spectrum, as study partners appear to more accurately update their concerns over time with regard to pathology, with these concerns less influenced by participants' mood symptomatology.

Keywords: Alzheimer’s disease; amyloid; anxiety; cognitive concerns; depression; longitudinal; mood; tau.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Study timeline.
FIGURE 2
FIGURE 2
The interaction between baseline participant GDS score and time to predict participant-rated (left) and study partner-rated (right) cognitive concerns using the current CFI. A significant interaction was seen between GDS and time when predicting participant-rated cognitive concerns (fixed estimate = –0.17, adj. p = 0.0012), in that participant concerns decreased over time in participants with higher GDS score at baseline (indicative of greater depressive symptomatology). The interaction between GDS score and time predicting study partner-rated cognitive concerns was not significant (fixed estimate = –0.003, adj. p = 0.964).
FIGURE 3
FIGURE 3
The interaction between baseline participant GAI score and time to predict participant-rated (left) and study partner-rated (right) cognitive concerns using the current CFI. A significant interaction was seen between GAI score and time when predicting participant-rated cognitive concerns (fixed estimate = –0.19, adj. p = 0.0450), in that participant concerns decreased over time in participants with higher GAI score at baseline (indicative of greater anxiety symptoms). The interaction between GAI score and time predicting study partner-rated cognitive concerns was not significant (fixed estimate = –0.12, adj. p = 0.380).
FIGURE 4
FIGURE 4
The interaction between baseline participant cerebral amyloid burden (FLR DVR) and time to predict participant-rated (left) and study partner-rated (right) cognitive concerns using the current CFI. A significant interaction was seen between amyloid and time when predicting study partner-rated cognitive concerns (fixed estimate = 4.07, adj. p = 0.0260), in that study partner concerns increased over time in participants with higher amyloid burden at baseline. The interaction between amyloid and time predicting participant-rated cognitive concerns was not significant (fixed estimate = 0.44, adj. p = 0.6350).
FIGURE 5
FIGURE 5
The interaction between baseline participant cerebral entorhinal tau burden (ER SUVR) and time to predict participant-rated (left) and study partner-rated (right) cognitive concerns using the current CFI. A significant interaction was seen between tau and time when predicting study partner-rated cognitive concerns (fixed estimate = 3.50, adj. p = 0.030), in that study partner concerns increased over time in participants with higher tau burden at baseline. The interaction between tau and time predicting participant-rated cognitive concerns was not significant (fixed estimate = –1.47, adj. p = 0.1620).
FIGURE 6
FIGURE 6
The interaction between baseline participant cerebral amyloid burden (FLR DVR) and time to predict participant-rated (left) and study partner-rated (right) cognitive concerns using the current CFI over only the first year of data collection (first four remote sessions). A significant interaction was seen between amyloid and time when predicting study partner-rated cognitive concerns (fixed estimate = 7.13, adj. p = 0.0330), in that study partner concerns increased over time in participants with higher amyloid burden at baseline. The interaction between amyloid and time predicting participant-rated cognitive concerns over the first year of data collection was not significant (fixed estimate = 0.20, adj. p = 0.940).
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