Memory for sequences of events impaired in typical aging

Abstract

Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to remember sequences of events, an important feature of episodic memory. Unlike existing paradigms, this task is nonspatial, nonverbal, and can be used to isolate different cognitive processes that may be differentially affected in aging. Here, we used this task to make a comprehensive comparison of sequence memory performance between younger (18-22 yr) and older adults (62-86 yr). Specifically, participants viewed repeated sequences of six colored, fractal images and indicated whether each item was presented "in sequence" or "out of sequence." Several out of sequence probe trials were used to provide a detailed assessment of sequence memory, including: (i) repeating an item from earlier in the sequence ("Repeats"; e.g., AB A: DEF), (ii) skipping ahead in the sequence ("Skips"; e.g., AB D: DEF), and (iii) inserting an item from a different sequence into the same ordinal position ("Ordinal Transfers"; e.g., AB 3: DEF). We found that older adults performed as well as younger controls when tested on well-known and predictable sequences, but were severely impaired when tested using novel sequences. Importantly, overall sequence memory performance in older adults steadily declined with age, a decline not detected with other measures (RAVLT or BPS-O). We further characterized this deficit by showing that performance of older adults was severely impaired on specific probe trials that required detailed knowledge of the sequence (Skips and Ordinal Transfers), and was associated with a shift in their underlying mnemonic representation of the sequences. Collectively, these findings provide unambiguous evidence that the capacity to remember sequences of events is fundamentally affected by typical aging.

Figure 1.

Behavioral design of the cross-species sequence task (Allen et al. 2014), adapted to compare the memory for sequences of events in younger and older adults. (A) The task was designed to capture the “flow of events” aspect of episodic memory (Tulving 1972, 1984, 2002), which conceptualizes an episode as a sequence of events segmented in time. Participants were tested on two phases of the task: a “no memory” phase in which highly familiar or predictable sequences were presented (e.g., an arrow rotating in clockwise steps), and a “memory” phase in which novel and arbitrary sequences of fractal images were presented. In each phase, participants received multiple presentations of four distinct, interleaved sequences on a computer screen and had to determine whether each image was presented “in sequence” (InSeq) or “out of sequence” (OutSeq). Participants were instructed to identify InSeq items by holding a key until the image disappeared, which signaled that the decision threshold (1.0 or 1.2 sec) had been reached, and OutSeq items by releasing the key as soon as possible (before the decision threshold). (B–D) Three different types of OutSeq probe trials were used during testing (Repeats, Skips, and Ordinal Transfers), which involve different cognitive processes and sequence representations. Note that probe trials could be presented in any sequence position except the first (i.e., sequences always began with an InSeq item). (B) Repeats occurred when an earlier item was presented a second time in the sequence (e.g., ABCDBF). Repeats can be detected with multiple cognitive strategies and were thus used to define the upper limit of the ability to identify OutSeq items. (C) Skips occurred when an item was presented too early in the sequence (e.g., ABEDEF, which skips over items C and D). Detecting Skips requires accurate predictions of upcoming items and thus performance on these probe trials was used as a sensitive measure of detailed sequence memory. (D) Ordinal Transfers occurred when an item from one sequence (e.g., UVWXYZ) was transferred to another sequence (e.g., ABCDEF) while retaining the item's original ordinal position (e.g., ABCDYF). Ordinal Transfers were used to help identify the type of sequence representations supporting task performance (i.e., sequential item–item associations or item-in-position associations).

Figure 2.

The memory for sequences of events was impaired in older adults. Performance was quantified using a sequence index (Equation 1; Allen et al. 2014), designated sequence detection index (SDI) in the “no memory” phase and sequence memory index (SMI) in the “memory” phase. (A) While younger and older adults performed at a comparably high level in the no memory phase (Age Group main effect: F_(1,69) = 0.040, P = 0.841), older adults were significantly impaired in the memory phase (F_(1,69) = 8.255, P = 0.005). These effects were consistent across the 1.0 and 1.2 sec decision thresholds (combined data shown). Moreover, sequence memory performance (SMI) declined linearly with age in older adults (B) a relationship that remained significant after regressing out the predictive value of SDI scores (SMI|SDI; C), indicating that age-related impairments were not simply due to nonmnemonic performance deficits. Note that the restricted age range in our sample of younger adults precluded a meaningful regression analysis. Regression lines are shown with corresponding 95% confidence bands. Age Group main effect: (*) P < 0.05, ns, P > 0.05.

Figure 3.

Older adults were impaired on Repeats when tested with a 1.0 sec decision threshold, but performed as well as younger adults with a 1.2 sec decision threshold. (A) Performance on Repeats, probe trials in which an item is a repeat presentation of one that occurred earlier in the sequence, in participants tested with a 1.0 sec decision threshold. The main bar graph shows overall accuracy for younger and older adults, and the inset graph shows the same data sorted by n-back distance (how many items back did the item first occur; e.g., ABCBEF is a two-back Repeat). Older adults were significantly impaired in identifying Repeats, a deficit that was consistent across n-back distances (Age Group main effect: F_(1,35) = 11.72, P = 0.002). (B) Corresponding data for participants tested with a 1.2 sec decision threshold. Both younger and older adults performed at a comparably high level, with no significant group differences overall (Age Group main effect: F_(1,34) = 0.4844, P = 0.491). Age Group main effect: (*) P < 0.05, ns, P > 0.05.

Figure 4.

Older adults were impaired on Skips and Ordinal Transfers, regardless of the decision threshold. For simplicity, graphs display data combining the two decision thresholds, as the same pattern of results was observed in the 1.0 and 1.2 sec groups (see text). (A) Performance on Skips, probe trials in which the sequence “skips ahead” and items appear too early in the sequence. The main bar graph shows overall accuracy on Skips, and the inset graph shows the same data sorted by n-forward distance (the number of items skipped; e.g., ABDDEF is a 1-forward Skip). Older adults exhibited an overall impairment in detecting Skips across n-forward distances (Age Group main effect: F_(1,69) = 7.23, P = 0.013), suggesting their memory of the sequences was less detailed thus limiting their ability to predict upcoming items. (B) Performance on Ordinal Transfers, probe trials in which an item is presented in the correct ordinal position but in the wrong sequence (e.g., AVCDEF; main bar graph: overall accuracy, inset graph: same data sorted by ordinal position of transferred item). This type of probe trial was used to help identify the type of mnemonic representations of sequences supporting performance on the task: correctly identifying Ordinal Transfers as OutSeq at asymptotic levels (at the level of Repeats) would be indicative of the use of sequential item–item associations (e.g., since V should not follow A), while accuracy at chance levels would be indicative of item-in-position associations (e.g., failing to detect that V is OutSeq because its ordinal position is correct). For both older and younger adults, Ordinal Transfers accuracy was significantly below that of Repeats (Older: t₍₃₀₎ = −13.745, P < 0.001; Younger: t₍₄₂₎ = −7.419, P < 0.001) and significantly above chance (Older: t₍₃₀₎ = 2.361, P = 0.025; Younger: t₍₄₂₎ = 10.654, P < 0.001), suggesting that both groups solved the task using a combination of sequential item–item associations and item-in-position associations. However, older adults identified significantly fewer Ordinal Transfers as OutSeq than younger subjects (Age Group main effect: F_(1,69) = 28.160, P < 0.001), suggesting they have a specific decline in memory for sequential item–item associations and thus relied mostly on item-in-position associations to remember sequences. Age Group main effect: (*) P < 0.05.

Figure 5.

Summary plot showing the effect of decision threshold on Repeats, Skips, and Ordinal Transfers accuracy. Older adults were impaired on Repeats in the 1.0 sec group, but not in the 1.2 sec group (Age Group × Decision Threshold interaction: F_(1,69) = 5.107, P = 0.027; A) While the impairment in the 1.0 sec group may be indicative of a working memory deficit in older adults, the “rescuing” effect of increasing the decision threshold indicates the impairment can be partially attributed to an age-related decline in processing speed. In contrast, impairments of older adults were consistent across decision thresholds for Skips (Age Group × Decision Threshold interaction: F_(1,69) = 0.389, P = 0.535; B) and Ordinal Transfers (Age Group × Decision Threshold interaction: F_(1,69) = 0.301, P = 0.585; C) and thus cannot simply be accounted by a reduction in processing speed. Age Group × Decision Threshold interaction effect: (*) P < 0.05; ns, P > 0.05.

Figure 6.

Performance on this novel sequence memory task, measured by SMI scores, provides a sensitive measure to characterize memory decline in aging. Linear regressions were performed to examine the relationship between SMI scores and two measures previously shown to be sensitive to age-related decline over the lifespan (Rey Auditory Verbal Learning Test, RAVLT; Behavioral Pattern Separation with Objects task, BPS-O; see Stark et al. 2013 for details). We found no statistically significant relationship between SMI and RAVLT scores (Immediate, Delayed, or Total scores; Delayed scores shown in A), nor between SMI and BPS-O scores (Recognition or Pattern Separation scores; Pattern Separation scores shown in C). The lack of relationship with SMI scores likely reflects the fact that the age-associated decline of RAVLT and BPS-O scores are typically measured over the lifespan (∼20–85 yr) and thus may not be strong predictors within the age range of the older adults group. In contrast, we observed significant relationships between age and SMI residuals after regressing out either the predictive value of RAVLT Delayed Scores (SMI|RAVLT; B) or BPS-O scores (SMI|BPS-O; D), indicating that performance on the sequence memory task captures age-related memory decline not already accounted by RAVLT or BPS-O tests. Regression lines are shown with corresponding 95% confidence bands.