Neuropsychology

© 2022 American Psychological Association 2023, Vol. 37, No. 2, 194–203

ISSN: 0894-4105 https://doi.org/10.1037/neu0000866

Past and Future Episodic Detail Retrieval Is Reduced Among Clinically Normal
Older Adults at Higher Genetic Risk for Late-Onset Alzheimer’s Disease
Mónica C. Acevedo-Molina1, Sean C. Thayer1, Kiley Horn1, Hanna Nkulu1, Lee Ryan1, 2, 3,
Jessica R. Andrews-Hanna1, 2, 4, and Matthew D. Grilli1, 2, 3
1
Psychology Department, University of Arizona
2
Evelyn F. McKnight Brain Institute, University of Arizona
3
Neurology Department, University of Arizona
4
Cognitive Sciences Department, University of Arizona
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Objective: Remembering and imagining personal events that are rich in episodic (i.e., event-specific) detail
is compromised in older adults who have mild cognitive impairment, a known risk factor for Alzheimer’s
disease dementia. Less clear is whether lower episodic detail generation is associated with higher risk for
Alzheimer’s disease dementia before mild clinical decline is detectable. Method: We compared past and
future autobiographical thinking in clinically normal older adult carriers of the Alzheimer’s disease-
associated apolipoprotein E e4 allele (APOE4; n = 39) to demographically and neuropsychologically
similar non-APOE4 carriers (n = 43). Results: APOE4 carriers showed a significant reduction for episodic
details when remembering past events (d = .47) and imagining future events (d = .46), but not for
nonepisodic details. Conclusions: These findings suggest that APOE4 is associated with a selective
reduction of episodic detail during past and future autobiographical thinking among clinically normal older
adults. Reduced episodic detail generation, therefore, may be an early cognitive associate of higher risk for
Alzheimer’s disease dementia.

Key Points
Question: Is lower episodic detail generation while imagining future events associated with higher
risk for Alzheimer’s disease dementia before mild clinical decline is detectable? Findings:
Clinically normal older adult APOE4 carriers not only showed a reduction in episodic detail
generation while remembering past events, but also while imagining future events, relative to
APOE4 noncarriers. Importance: Our findings suggest that reduced episodic detail generation
is associated with higher risk for Alzheimer’s disease dementia in clinically normal older adults.
Next Steps: Future research could investigate the neural mechanisms behind this Alzheimer’s risk-
related selective reduction in episodic detail generation, in particular in relationship to race,
ethnicity, and APOE4.

Keywords: neuropsychology, autobiographical memory, future thinking, apolipoprotein E, aging

Supplemental materials: https://doi.org/10.1037/neu0000866.supp

This article was published Online First November 28, 2022.
Mónica C. Acevedo-Molina https://orcid.org/0000-0003-3835-0391
Mónica C. Acevedo-Molina and Matthew D. Grilli received funding from
Grants F31 AG069443 and R03 AG060271, respectively, from the National
Institute on Aging. Matthew D. Grilli received funding from Grant
1UF1AG046150-01 from the GeneMatch. The research was also supported
by National Institutes of Health (NIH). The content is solely the responsi-
bility of the authors and does not necessarily represent the official views of
the National Institutes of Health. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
Mónica C. Acevedo-Molina played lead role in conceptualization, data
curation, formal analysis, funding acquisition, investigation and method-
ology and equal role in visualization, writing of original draft and writing of
review and editing. Sean C. Thayer played lead role in methodology and
project administration and equal role in writing of review and editing. Kiley
Horn played equal role in data curation and writing of review and editing.
Hanna Nkulu played equal role in data curation and writing of review and
editing. Lee Ryan played supporting role in conceptualization and meth-
odology and equal role in writing of review and editing. Jessica R.
Andrews-Hanna played lead role in conceptualization, investigation, meth-
odology and supervision and equal role in writing of review and editing.
Matthew D. Grilli played lead role in conceptualization, formal analysis,
funding acquisition, investigation, methodology, resources and supervision
and equal role in visualization, writing of original draft and writing of
review and editing.
Correspondence concerning this article should be addressed to Mónica
C. Acevedo-Molina, Psychology Department, University of Arizona, 1503
East University Boulevard, P.O. Box 210068, Tucson, AZ 85721, United
States. Email: macevedomolina@email.arizona.edu

194
 PAST AND FUTURE EPISODIC DETAIL
The human mind has an impressive capacity to remember the
past and imagine the future in rich episodic detail, meaning in a
vivid, event-specific way (Suddendorf & Corballis, 2007). It is well-
established that older adults with mild cognitive impairment, a
known risk factor for Alzheimer’s disease dementia, show reduced
episodic detail while remembering and imagining personal events,
compared to clinically normal older adults (Barnabe et al., 2012;
Leyhe et al., 2009; Murphy et al., 2008). This cognitive reduction
is potentially highly impactful, as generating episodically detailed
past and future personal events influences decision making (Mok
et al., 2020; Schacter et al., 2017), problem-solving (Hallford et al.,
2022; Sheldon et al., 2011), and identity (Addis & Tippett, 2004;
Eustache et al., 2016). Considering the importance of episodic
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detail retrieval to daily functioning, and evidence of robust reduc-
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tions already at the stage of mild cognitive impairment, it is critical
to reveal how early these deficits are detectable.
Reduced Past Episodic Detail Retrieval Among
apolipoprotein E e4 Carriers
Recent work suggests that alterations in episodic detail may in
fact be associated with known markers of Alzheimer’s disease risk
in clinically normal older adults. Of relevance to the present study,
we recently found that clinically normal older adult carriers of the
e4 allele of the apolipoprotein E gene (APOE4) recall past events in
less episodic detail relative to demographically similar noncarriers
of APOE4, whereas nonepisodic narrative content, like background
knowledge, is unaffected (Grilli et al., 2018). Given that APOE4
accounts for as much as half of all late-onset cases of Alzheimer’s
disease (Corder et al., 1993; Saunders et al., 1993), these findings
suggest that altered autobiographical thinking may be part of the
protracted trajectory of cognitive decline leading to clinical symp-
toms (Caselli et al., 2020), and may be evident before many standard
cognitive test scores are affected. This conclusion is supported by
additional work on subjective cognitive decline (Bruus et al., 2021)
and the relationship between preclinical amyloid and autobiograph-
ical knowledge (Buckley et al., 2014).
Future Episodic Detail Generation Among
APOE4 Carriers
In light of the potential significance of reduced episodic detail
to detecting the cognitive impact of higher Alzheimer’s disease risk
in clinically normal older adults, we aimed to replicate and extend
our earlier findings in the present study by examining future-
oriented autobiographical thinking. Some theories propose that
the brain mentally constructs past and future events (or atemporal
scenes) using similar cognitive processes, and an overlapping brain
network (Addis, 2020; Andrews-Hanna & Grilli, 2021; Irish, 2020;
Mullally & Maguire, 2014). However, whether APOE4 status, or
any Alzheimer’s disease risk factor for that matter, impacts future-
oriented episodic detail generation in clinically normal older adults
is not known. Closing this gap would reveal whether the effect of
APOE4 on episodic detail has a broad impact on many forms of
autobiographical cognition that support daily functioning, such as
goal achievement and weighing immediate versus delayed rewards
(Schacter et al., 2012).
Investigating future thinking also can shed light on the cognitive
processes that contribute to reduced episodic detail generation.
195
Revealing the cognitive mechanisms through which higher Alzhei-
mer’s disease risk can affect remembering is important for test
development and could lead to more precise clinical endpoints. One
candidate cognitive process for reduced episodic detail is the
ability to bind elements during event construction (Gaesser et al.,
2013; Romero & Moscovitch, 2012), a cognitive process also
known as “relational processing” (Eichenbaum, 1993). Relational
processing involves integrating perceptual and conceptual details
within elements of an event (e.g., what an individual was wearing)
and across elements of an event (e.g., the people, place, and time
of an event) to construct a holistic, complex mental experience
(Addis, 2018; Gaesser et al., 2013; Romero & Moscovitch, 2012).
The role of relational processing in remembering is difficult to
isolate, given that event memories may become more unified over
repeated retrievals, and demands on relational processing might
be reduced and uneven across memories (Addis, 2018). Imagining
novel events requires that within-element and across-element details
from past events are bound together in a way never done before
(Gaesser et al., 2013; Romero & Moscovitch, 2012; Wiebels et al.,
2020). Therefore, examining future thinking is a theory-driven way to
evaluate relational processing’s candidacy as a cognitive mechanism
behind the APOE4-associated reduction in episodic detail generation.
The Present Study
To investigate the impact of APOE4 status on past and future
thinking, and to gain insight into the role of relational processing
in this reduction, we adopted an autobiographical thought task that
measures both past and future thinking, and does so in a way that
ensures future thinking places higher demands on relational proces-
sing (Addis et al., 2010). We hypothesized that if reduced episodic
detail generation reflects a core feature of APOE4’s impact on
autobiographical cognition at nonclinical stages, clinically normal
APOE4 carriers should show reduced episodic detail generation not
only while remembering personal events, but also while imagining
novel future personal events. We also hypothesized that if relational
processing is a primary source of the APOE4-associated reduction
in episodic detail, clinically normal APOE4 carriers should show a
greater disruption to episodic detail generation while imagining
future events, in comparison to their deficit while remembering
past events.
Method
Participants
Eighty-five older adults were enrolled in the present study. To be
eligible, participants had to be between the ages of 60–80 and
clinically normal based on an established actuarial, profile-based
approach using a comprehensive battery of neuropsychological
tests (Bondi et al., 2014). Neuropsychological eligibility was based
on two test scores in learning and memory (total learning and long
delay-free recall from the California Verbal Learning Test, Second
Edition, Delis et al., 2000), processing speed/executive functioning
(Trail Making Test A and B, Reitan & Wolfson, 1985), and language
(total naming on the Boston Naming Test, Kaplan et al., 2001, and
total category fluency on the animal trial of the Controlled Oral
Word Association Test, Benton et al., 1994). In this actuarial
approach, individuals are considered clinically normal if neither
 196 ACEVEDO-MOLINA ET AL.

of the following were met: (a) they performed more than 1 standard
deviation below the age-corrected (and education-corrected if avail-
able) normative mean on both scores in one cognitive domain or
(b) they performed more than 1 standard deviation below the age-
corrected (and education-corrected if available) normative mean
on one test in three cognitive domains. Notably, in this actuarial
approach, subjective cognitive decline does not factor into a deter-
mination of mild cognitive impairment. In addition, to be included
participants had to score below the cutoff score of 16 for depression
on the Center for Epidemiological Studies Depression Scale
(Radloff, 1977), they had to deny a remarkable history of neurologic
conditions that could have cognitive effects, and they had to report
being independent in activities of daily living. Informed written
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education, or intelligence, p’s > .21. Table 1 also reports the
breakdown of heterozygotes and homozygotes for APOE4.
Sample Size Determination
The present study is part of a larger project involving behavioral
testing and a functional magnetic resonance imaging session. We
aimed to recruit 85 participants for the project, knowing that a small
number of participants might need to be removed for various
reasons. For the present study, we knew a priori that with a sample
size ≥80, and α = .05, we had high power (1−β) = .95, to detect an
interaction between task (past vs. future) and APOE4 status for
episodic detail generation, assuming a small-to-medium effect

consent was provided by all participants, and all study procedures (partial η2 = .04).
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were in compliance with the institutional review board at the

University of Arizona.
Of the 85 participants enrolled, 82 completed the task require-
ments. One person did not return for their second session. We
discontinued two additional participants before completing
the past and future thinking task because of confusion about
the task.
Demographics for the 82 participants, split by APOE4 status, are
shown in Table 1. These individuals were recruited from existing
databases in which APOE status was already known through cheek
swab or dried blood spot samples (i.e., in our laboratory, and with
GeneMatch, Langbaum et al., 2019). This enabled us to target a
planned ratio of approximately 50:50 APOE4 carrier versus non-
carrier status, while matching on basic demographics. We achieved
this plan by conducting multiple waves of email and phone invita-
tions that were balanced on APOE status, and by monitoring
enrollment numbers by APOE status. No individual was from
Grilli et al. (2018). Table 1 shows that the APOE4 carriers did
not significantly differ from the APOE4 noncarriers on age, gender,
Procedure
Past and Future Thinking Task
We used an adapted version of the recombination task developed
by Addis and colleagues (Addis et al., 2010). In our version, the task
unfolded over two sessions, separated by 5–7 days. In Session 1,
participants were asked to generate 16 memories from approxi-
mately the past 5 years. Participants were informed that each
memory must contain what they considered a “very vivid and
detailed” person, object, and place, and that these details could
not repeat across memories. To facilitate retrieval, participants were
cued with 16 pictures (selected with Google Image searches), which
roughly corresponded to the meaning of 16 words selected from the
Clark and Paivio norms (Clark & Paivio, 2004) that were high on
frequency (M = 1.84), imageability (M = 5.91), and concreteness
(M = 6.71). Participants were told that they need not rely on pictures
to cue retrieval. The first trial was for practice, and therefore, there
were 15 critical memory generation trials.

Table 1
Sample Characteristics by APOE Status

Variable Carriers (N = 39)a Noncarriers (N = 43) Effect sizes (Cohen’s d)

Demographics
Age M(SD) 69.2 (6.9) 68.5 (5.1) .12
Education 16.7 (2.0) 16.9 (1.6) .10
Male N(%) 16 (41) 12 (28) Odds ratio = 1.80
Race N(%)
Black or African American 2 (5) 0
White 37 (95) 42 (98)
Asian 0 1 (2)
Ethnicity N(%)
Hispanic or Latino 2 (5) 1 (2)
Not Hispanic or Latino 37 (95) 42 (98)
Neuropsychological testing scores Mraw(SD)
CVLT-2
Trials 1–5 50.3 (10.6) 51.6 (8.4) .14
Long delay-free recall 11.1 (3.3) 12.1 (2.8) .34
BNT 57.5 (2.1) 57.9 (2.0) .18
Animal fluency 21.4 (4.4) 22.5 (5.1) .25
Trails A 32.3 (10.4) 30.6 (7.7) .18
Trails B 79.0 (35.1) 66.6 (23.8) .42
WAIS-IV VCI 121.5 (9.6) 123.8 (11.9) .22
Note. APOE = apolipoprotein E; CVLT-2 = California Verbal Learning Test 2; BNT = Boston Naming Test; WAIS IV =
Wechsler Adult Intelligence Scale IV; VCI = Verbal Comprehension Index.
a
Among the APOE4 carriers five participants were homozygotes and 34 participants were heterozygotes.
 PAST AND FUTURE EPISODIC DETAIL
Between Sessions 1 and 2, an experimenter randomly selected five
memories to serve as memory trials. These people, object, and place
detail triplets were preserved. The future thinking trials were created
by re-sorting the people, objects, and places from the remaining 10
memories. The experimenter ensured that each recombined triplet was
entirely new. Five of these recombined triplets were randomly selected
as future thinking trials, two were selected for practice, and three were
available in case a selected triplet was reported as improbable.
In Session 2, participants were informed that they would be asked
to revisit some memories retrieved in Session 1, and imagine several
new events happening in approximately the next 5 years. Participants
were shown the triplets using slides on PowerPoint, along with the
instruction to either remember the previously generated past event
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from the past 5 years or imagine a future event happening in the next
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5 years involving the newly combined person, place, and object. The
order of the past and future thinking trials was quasirandomized such
that no more than two trials of either task were presented sequentially.
Participants were instructed to focus on the details that described the
unique features of the event. They also were told that they needed to
describe the three details presented in the triplet. They were given
4 min per trial. If presented with an improbable future event (e.g.,
imagining a future event with someone who passed away), partici-
pants were asked to inform the experimenter, who would select a new
triplet. The participants’ responses were audio recorded.
COVID-19 Pandemic Mitigation
Eight of our participants had to complete Session 2 using video
conferencing (Zoom for Health), because we halted in-person research
at the start of the COVID-19 pandemic, and then again briefly during a
surge in infections. A total of 49 participants were tested before the
COVID-19 pandemic; 33 participants were tested during the pandemic
with enhanced health measures in place. In-person research after the
start of the pandemic involved enhanced health measures, including
masks. Both prepandemic versus postpandemic and in-person versus
zoom were accounted for as nuisance covariates.
Detail Scoring
We used the Autobiographical Interview scoring protocol devel-
oped by Levine et al. (2002). In this protocol, trained raters break each
narrative down into detail segments, and then score these segments as
either “internal” or “external” to the main event being described.
Internal details are typically characterized as episodic details, includ-
ing event, time, place, perceptual, and thought/emotion details.
External details include semantic details, along with repetitions,
meta or editorial comments, and descriptions of external events.
To create a more reliable estimate of internal and external detail
for each participant, two trained raters who were blind to APOE4
status scored each trial. The average of the two scores was used in the
analyses. Reliability between the two scorers for each participant was
consistently good for internal and external details in past and future
thinking trials, intraclass correlation coefficients = .8–.90.
Statistical Analyses
Demographic and neuropsychological data (reported in Table 1)
were compared between APOE4 carriers and noncarriers using
independent samples t tests.
197
To test the hypotheses that the APOE4-associated reduction in
episodic detail generation extended to, and may be greater for, future
thinking, we ran an analysis of variance with factors of group
(APOE4 carriers vs. noncarrier), detail type (mean internal vs.
external per memory or future thinking trial) and task (remembering
vs. future thinking) with pre- versus post-COVID status and in-
person versus online status added as nuisance covariates.
In follow-up exploratory analyses, we asked whether the effect of
Alzheimer’s disease risk would be reflected in APOE4 homozygote
versus heterozygote status. Given the small sample sizes for these
follow-up analyses, we used the nonparametric Mann–Whitney U
test to compare APOE4 noncarriers to APOE4 heterozygotes
and then homozygotes, and we collapsed across remembering
and future thinking for internal and external detail generation. As
another exploratory analysis, we asked whether individual differ-
ences in internal detail generation while remembering was signifi-
cantly related to internal detail generation while imagining future
events with a Pearson correlation analysis.
All analyses were performed with Jamovi (The Jamovi Project,
2021), which ran the afex package and the psych package in R
(R Core Team, 2021). Figures were created in R using ggplot2.
Transparency and Openness
De-identified data for the present study are deposited here: https://
osf.io/gbpfa/?view_only=69c8922d834645c3b67be07a3cd74457.
The design and analyses for this study were not preregistered.
Results
Neuropsychological Profiles
The APOE4 carriers and noncarriers did not significantly differ on
any of the eight neuropsychological scores used to determine study
eligibility, p’s ≥ .06 (Table 1).
Remembering Versus Future Thinking
Figure 1 shows internal and external detail generation for remem-
bering (A) and future thinking (B) separately. Supplemental Table 1
reports means and standard deviations. When we examined memory
and future thinking trials entered into a single model, we found
that while there was not a significant effect of group, F(1,78) = 1.25,
p = .27, partial η2 = .02, there was a significant effect of detail type,
F(1,78) = 39.9, p < .001, partial η2 = .34, and a significant
interaction between group and detail type, F(1,78) = 8.39, p =
.005, partial η2 = .10. Planned simple effect analyses revealed that
this interaction reflected the fact that there was an overall effect of
APOE4 status on internal detail, t(78) = 2.29, p = .02, but not on
external detail, t(78) = 1.15, p = .25.
This model further showed that, as intended, the recombination
manipulation for the future thinking trials significantly increased
difficulty for internal detail generation, as shown by a significant
effect of task, F(1,78) = 25.01, p < .001, partial η2 = .24, and a
significant interaction between task and detail type, F(1,78) = 40.41,
p < .001, partial η2 = .34, with planned simple effect analyses
showed that while internal detail generation significantly dropped
from memory to future thinking, t(78) = 3.33, p < .001, external
details did not, t(78) = 0.31, p = .76.
 198 ACEVEDO-MOLINA ET AL.

Figure 1
Internal and External Details Generated by Group in Past and Future Events
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Note. (A) Relative to non-APOE4 carriers (purple; dark grey) APOE4 carriers (yellow; light grey)
tended to generate less internal (i.e., episodic) detail, but not less external (i.e., nonepisodic) detail while
remembering past personal events. (B) Relative to non-APOE4 carriers, APOE4 carriers tended to
generate less internal detail, but not less external detail while imagining future personal events. The boxes
in the boxplots capture the 25th to 75th percentile, with the 50th percentile represented by the dark line
intersecting the boxes. The whiskers capture 1.5 standard deviations above and below the 75th and 25th
percentiles, respectively. Each participant is represented by a dot, with a minor jitter applied for
visualization of all dots. APOE4 = apolipoprotein E e4. See the online article for the color version
of this figure.

Finally, this model showed that although future thinking placed
higher demands on relational processing, the effect of APOE4
status was not significantly moderated by this task manipulation.
That is, there was not a significant interaction between task and
APOE4 status, F(1,78) = 0.72, p = .40, partial η2 = .01, nor was
there a three-way interaction between these factors and detail type,
F(1,78) = 0.45, p = .50, partial η2 = .006.
Despite the lack of a significant three-way interaction, we none-
theless examined whether the effect of APOE4 status on internal
detail was evident in both the remembering and future thinking
 PAST AND FUTURE EPISODIC DETAIL
tasks, given the importance of such an outcome to evaluating
whether we had replicated and extended Grilli et al. (2018), and
for estimating effect sizes for the APOE4 reduction in both
remembering and future thinking. Here, we found that there was
in fact a significant interaction between APOE4 status and detail
type for both remembering and future thinking, when analyzed
separately, remembering: F(1,78) = 6.39, p = .01, partial η2 = .08;
future thinking: F(1,78) = 7.51, p = .01, partial η2 = .09. In both
cases, while internal details were significantly reduced, remember-
ing: t(78) = 2.15, p = .04, d = .47; future thinking: t(78) = 2.13, p =
.04, d = .46, external details did not significantly differ by APOE4
status, remembering: t(78) = 0.63, p = .53, d = .14; future thinking:
t(78) = 1.52, p = .13, d = .32.
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Effect of APOE4 Homozygosity Versus Heterozygosity
Means and standard deviations for APOE4 homozygotes and
APOE4 heterozygotes are reported in Supplemental Table 2.
These exploratory analyses further suggest that the reduction in
internal detail generation was related to the magnitude of genetic
risk for Alzheimer’s disease. Although internal details were
numerically reduced in both APOE4 heterozygotes and homo-
zygotes relative to APOE4 noncarriers, the difference was only
significant for the homozygotes (heterozygotes: U = 567, p = .09,
rank biserial correlation = .22; homozygotes, U = 43, p = .03, rank
biserial correlation = .60). Neither APOE4 heterozygotes nor
homozygotes significantly differed from APOE4 noncarriers for
external detail (heterozygotes: U = 626, p = .28, rank biserial
correlation = .14; homozygotes: U = 74, p = .28, rank biserial
correlation = .31).
Figure 2
Correlation Between Internal Detail Generation in Past and Future Events
Note. The shaded region represents the 95% confidence interval of the regression line for APOE4
carriers and noncarriers separately. APOE4 = apolipoprotein E e4.
199
Correlation Between Past and Future Detail
While the past and future thinking findings show a consistent
effect of APOE4 status, they do not inform whether individuals who
tend to recall past events in less episodic detail also tend to imagine
future events in the same way. We therefore conducted an explor-
atory analysis in which we examined the Pearson correlation
between participants’ mean episodic detail generation for past
events with that of their mean episodic detail for future events.
Past and future episodic detail generation were highly correlated, r =
.73, p < .001. As shown in Figure 2, this high correlation was
evident in both APOE4 carriers (r = .71, p < .001) and noncarriers
(r = .75, p < .001).
Discussion
The present findings strengthen the conclusion that autobiograph-
ical remembering among clinically normal older adult APOE4
carriers is selectively reduced in episodic (internal) detail relative
to demographically and neuropsychologically similar non-APOE4
carriers. Not only do these findings demonstrate the replicability
of this reduction, but they do so in a large sample of older adults
more than double that of Grilli et al. (2018). The effect size for the
reduction in remembering specifically (d = .47) further suggests
that the impact on episodic detail generation while recalling past
events is moderate. Reduced episodic detail retrieval while remem-
bering, therefore, appears to be a robust and replicable associate of
higher risk for Alzheimer’s disease, before mild cognitive
impairment has emerged.
Consistent with the idea that past and future thinking rely on a
common set of cognitive processes and underlying brain network
 200 ACEVEDO-MOLINA ET AL.
(Andrews-Hanna & Grilli, 2021; Addis, 2020; Irish, 2020), we
found that APOE4 carriers also showed a reduction in episodic
(internal), but not nonepisodic (i.e., external), detail while imagining
future personal events. Like the memory results, the magnitude of
this APOE4 effect for future thinking was moderate (d = .46). In
addition, we found that episodic detail generation for past and
future events were highly correlated. Both APOE4 carrier and
noncarrier individuals who tended to recall past events in little
episodic detail also tended to imagine future events in a less
episodically rich way. This suggests that clinically normal older
adults tend to be highly reliable in how vividly they typically
remember the past and imagine their future.
What is the cause of the APOE4-associated breakdown in
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episodic detail generation? At a cognitive level, we investigated
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whether reduced relational processing, or event construction, could
be a key source of the problem. Episodic (internal), but not external,
detail generation was significantly lower for future thinking relative
to remembering, indicating that the future thinking task increased
demands on relational processing as intended. However, the find-
ings appear not to support a relational processing explanation for
the APOE4 effect on autobiographical thinking, because APOE4
carriers did not show a disproportionate drop from past to future
thinking. Therefore, other cognitive processes involved in autobio-
graphical thinking, such as how thoughts are searched for and
narrated (Acevedo-Molina et al., 2020; Bluck et al., 2016; Wank
et al., 2020), may be responsible for this APOE4 effect. It is also
possible that mental scene construction, a specific type of relational
processing not isolated in this study, is responsible for the drop
in episodic detail generation (Hassabis et al., 2007). Event construc-
tion is a complex process (Gaesser et al., 2013; Romero &
Moscovitch, 2012), and perhaps not all forms of relational proces-
sing within and across items and context are the same. Whereas
our study involved integrating a diversity of event elements includ-
ing people, places, and items, we might have found different results
if we focused the role of relational processing on piecing together
the core elements of the scene (Hassabis et al., 2007; Summerfield
et al., 2010).
In regard to understanding the neural underpinnings of this
APOE4-associated reduction in episodic detail generation, recent
research has revealed that a number of brain regions, including
the hippocampus and its cortical connections, are involved in
remembering the past, simulating the future, and imagining novel
scenes (Addis et al., 2007; Andrews-Hanna & Grilli, 2021; Hassabis
et al., 2007; Maguire, 2001; Schacter et al., 2012; Summerfield et al.,
2010). The medial temporal lobe subsystem of the default network,
which incorporates the hippocampus and many of its cortical and
subcortical connections (including the parahippocampal cortex,
retrosplenial cortex, the posterior cingulate cortex, and the inferior
parietal lobe), may have an essential role in the sort of cognitive
demands required of retrieving and (re)binding vivid, contextualized
elements of past events, future events, and atemporal scenes,
possibly working collaboratively with the medial prefrontal cortex
(Andrews-Hanna & Grilli, 2021; Gaesser et al., 2013; Romero et al.,
2019; Sheldon et al., 2019; Summerfield et al., 2010). In fact, recent
neuroimaging research using the same Autobiographical Interview
scoring approach as the present study has found that individual
differences in structural and functional measures of parts of the
default network medial temporal lobe subsystem significantly
relate to episodic (internal) detail remembering among cognitively
normal older adults (Matijevic et al., 2022; Memel et al., 2020; also
Setton et al., 2022, in a sex specific pattern).
The hippocampus and its cortical connections also are prime
targets of Alzheimer’s disease pathology (Hojjati et al., 2021; Ingala
et al., 2021). Both amyloid and tau appear to compromise portions
of the default network medial temporal lobe subsystem early in the
disease (Foster et al., 2018; Jones et al., 2017; Palmqvist et al., 2017;
Rodrigue et al., 2012; Schultz et al., 2017; Sheline et al., 2010).
Relatedly, prior studies have shown that Alzheimer’s disease risk-
related neural alterations in the hippocampus and its cortical
connections are linked to cognitive mechanisms that may be needed
to retrieve episodic details of past events, including spatial context
memory, verbal memory recall, and cognitive control (Rajah et al.,
2017; Shafer et al., 2021; Westlye et al., 2012). Older adult APOE4
carriers have deficits in other hippocampally dependent memory
mechanisms that may also have a role in episodic detail generation,
such as autobiographical category fluency and memory consolida-
tion (Grilli et al., 2021; Tort-Merino et al., 2020; Zimmermann &
Butler, 2018). Therefore, while the present study raises doubt
about the role of relational processing, other cognitive mechanisms
dependent on the hippocampus and its cortical connections may
account for APOE4-associated reductions in episodic detail gener-
ation. Future research also can directly investigate whether reduced
episodic detail generation is connected to amyloid or tau in the
default network and whether APOE4 moderates this relationship.
However, we also acknowledge that neural differences have been
found in APOE4 carriers that may not be specific to Alzheimer’s
disease (Ryan et al., 2011). Whether reduced episodic detail gener-
ation is more generally capturing risk for cognitive decline needs
to be considered.
An exploratory analysis revealed that APOE4 homozygosity was
significantly associated with a reduction in episodic (internal) detail
generation relative to APOE4 noncarriers. In comparison, hetero-
zygosity was associate with a numerical, but not statistically signif-
icant, reduction relative to APOE4 noncarriers. One intriguing
implication of these analyses is that reductions in episodic detail
generation while remembering and imagining events tracks with the
degree of APOE4-related Alzheimer’s disease risk, such that
one allele introduces a degree of risk that is less than that of two
alleles. However, these findings should be investigated further as
this was an exploratory analysis based on smaller sample sizes. It
would also be interesting to compare the impact of APOE4 on
remembering and imagining relative to other Alzheimer’s disease
risk factors in clinically normal older adults, such as subjective
cognitive decline (Bruus et al., 2021; Pike et al., 2021; van Harten
et al., 2018). Notably, although our inclusion criteria included
being independent in functional activities of daily living, we did
not formally assess subjective cognitive decline, which is a limita-
tion of the present study.
Finally, it is essential to note that our study sample was not
racially or ethnically diverse. Given that autobiographical memories
inherently come from a person’s cultural framework and back-
ground knowledge, we might expect autobiographical memory tests
to be culturally appropriate and sensitive to Alzheimer’s disease risk
across groups. However, we must also acknowledge that cultural
differences may influence autobiographical remembering and future
thinking. For instance, Wang et al. (2011) examined episodic
autobiographical memory specificity differences between young
East Asians and European Americans and found that relative to
 PAST AND FUTURE EPISODIC DETAIL
East Asians, European Americans produced more episodic details
during memory retrieval. Indeed, the social–cultural environment
in which a person is raised appears to influence how they share
stories. For instance, Euro-American mothers tend to engage in
highly elaborative conversations with their children, which may
influence their ability to recall and recount personal experiences. As
a result, by the age of three, Euro-American children can recall
more specific memory information relative to Chinese children (Han
et al., 1998; Wang, 2004; Wang et al., 2011). Such cultural
differences may be related to variability in narrative style, language
use or bilingualism, self-other prioritization, and interviewer–
interviewee factors (Ross & Wang, 2010). Moreover, research
examining the relationship between race, ethnicity, and APOE4,
This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
in particular, has found that these factors may also influence how
This document is copyrighted by the American Psychological Association or one of its allied publishers.
Alzheimer’s disease-associated cognitive risk manifests in different
populations. For instance, the effects of APOE4 may be weaker
among African Americans than Caucasians (Maestre et al., 1995;
Tang et al., 1998). Similarly, a study by Farrer and colleagues
(Farrer et al., 1997) found that APOE4 Alzheimer’s disease-
associated risk was also attenuated in Hispanics. Given these
findings, had our sample been more diverse, it might have been
possible to see different relationships between episodic detail
generation and APOE4 among different racial groups.
While questions remain, the fact that autobiographical thinking,
both past and future-oriented, tends to be altered in clinically normal
older adult APOE4 carriers is noteworthy. The findings from our
study are especially striking in that our sample was otherwise a
high functioning group of older adults with no significant differ-
ences from non-APOE4 carriers on neuropsychological scores.
Given that autobiographical thinking plays a significant role in
everyday decision making, planning, problem-solving, socializing
and self-reflection, our findings raise the possibility that reduced
episodic detail could affect these “real world” cognitive demands
prior to clinical decline. Our findings also suggest that autobio-
graphical memory testing is worth further consideration as a poten-
tially useful clinical endpoint.
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Received March 28, 2022
Revision received August 17, 2022
Accepted August 19, 2022 ▪