Visual short-term memory impairments in presymptomatic familial Alzheimer's disease: A longitudinal observational study.
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ABSTRACT:
SUBMITTER: Pavisic IM
PROVIDER: S-EPMC8589962 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI. Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers - who performed similarly to healthy controls on standard neuropsychological tests - had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore provide a sensitive cognitive biomarker for MTL dysfunction in a range of diseases including AD.
| S-EPMC4865502 | biostudies-literature
Project description:The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer's disease (AD) remains unclear. Research suggests that eye movements may serve as indirect surrogates to investigate VSTM. Yet, investigations in preclinical populations are lacking. Fifty-two individuals from a familial Alzheimer's disease (FAD) cohort (9 symptomatic carriers, 17 presymptomatic carriers and 26 controls) completed the "Object-localisation" VSTM task while an eye-tracker recorded eye movements during the stimulus presentation. VSTM function and oculomotor performance were compared between groups and their association during encoding investigated. Compared to controls, symptomatic FAD carriers showed eye movement patterns suggestive of an ineffective encoding and presymptomatic FAD carriers within 6 years of their expected age at symptom onset, were more reliant on the stimuli fixation time to achieve accuracy in the localisation of the target. Consequently, for shorter fixation times on the stimuli, presymptomatic carriers were less accurate at localising the target than controls. By contrast, the only deficits detected on behavioural VSTM function was in symptomatic individuals. Our findings provide novel evidence that encoding processes may be vulnerable and weakened in presymptomatic FAD carriers, most prominently for spatial memory, suggesting a possible explanation for the subtle VSTM impairments observed in the preclinical stages of AD.
| S-EPMC8062689 | biostudies-literature
Project description:Are the information processing steps that support short-term sensory memory common to all the senses? Systematic, psychophysical comparison requires identical experimental paradigms and comparable stimuli, which can be challenging to obtain across modalities. Participants performed a recognition memory task with auditory and visual stimuli that were comparable in complexity and in their neural representations at early stages of cortical processing. The visual stimuli were static and moving Gaussian-windowed, oriented, sinusoidal gratings (Gabor patches); the auditory stimuli were broadband sounds whose frequency content varied sinusoidally over time (moving ripples). Parallel effects on recognition memory were seen for number of items to be remembered, retention interval, and serial position. Further, regardless of modality, predicting an item's recognizability requires taking account of (1) the probe's similarity to the remembered list items (summed similarity), and (2) the similarity between the items in memory (inter-item homogeneity). A model incorporating both these factors gives a good fit to recognition memory data for auditory as well as visual stimuli. In addition, we present the first demonstration of the orthogonality of summed similarity and inter-item homogeneity effects. These data imply that auditory and visual representations undergo very similar transformations while they are encoded and retrieved from memory.
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Project description:BackgroundTo investigate how serum neurofilament light (NfL) concentration changes through the course of disease in familial Alzheimer's disease (FAD) and to assess when NfL concentration first increases.MethodsNfL was measured using an ultrasensitive immunoassay in 117 serum samples from 61 individuals from families with PSEN1 or APP mutations in a longitudinal study (mean ± SD = 1.9 ± 1.1 visits/patient; inter-visit interval = 1.8 ± 1.1 years). The relationship between NfL concentration and estimated years to/from symptom onset (EYO) was modelled using linear regression, including all time points and robust standard errors to allow for repeated measurements, adjusting for age at visit and sex. Also, for the 27 participants who became symptomatic (during or before the study), NfL concentration was also modelled against known actual years to/from onset (AYO).ResultsThere were 15 non-carriers and 46 mutation carriers (21 symptomatic; 25 presymptomatic). NfL concentration was increased (p = 0.045) in mutation carriers compared with non-carriers 15 years prior to expected symptom onset, increasing progressively thereafter. There was a significant inter- and intra-individual variability in the longitudinal pattern of change. Modelling NfL for the 27 mutation carriers with known AYO also showed a progressive increase over time.ConclusionsThere is evidence that serum NfL is increased more than a decade before the onset of clinical symptoms in FAD and rises thereafter. While there is variability in change over time, both within and between individuals, and more work is needed to understand the sources of this variability, serum NfL remains a promising, accessible biomarker of early neurodegeneration in presymptomatic Alzheimer's disease.
| S-EPMC6383280 | biostudies-literature
Project description:Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer's disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p < 0.001) and presymptomatic mutation carriers (p < 0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85-0.98]) and presymptomatic (EYO ≥ -7 years) (AUC 0.86 [95% CI 0.72-0.94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p = 0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology.
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Project description:Visual short-term memory (VSTM) is thought to help bridge across changes in visual input, and yet many studies of VSTM employ static displays. Here we investigate how VSTM copes with sequential input. In particular, we characterize the temporal dynamics of several different components of VSTM performance, including: storage probability, precision, variability in precision, guessing, and swapping. We used a variant of the continuous-report VSTM task developed for static displays, quantifying the contribution of each component with statistical likelihood estimation, as a function of serial position and set size. In Experiments 1 and 2, storage probability did not vary by serial position for small set sizes, but showed a small primacy effect and a robust recency effect for larger set sizes; precision did not vary by serial position or set size. In Experiment 3, the recency effect was shown to reflect an increased likelihood of swapping out items from earlier serial positions and swapping in later items, rather than an increased rate of guessing for earlier items. Indeed, a model that incorporated responding to non-targets provided a better fit to these data than alternative models that did not allow for swapping or that tried to account for variable precision. These findings suggest that VSTM is updated in a first-in-first-out manner, and they bring VSTM research into closer alignment with classical working memory research that focuses on sequential behavior and interference effects.
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Project description:A central question in the study of visual short-term memory (VSTM) has been whether its basic units are objects or features. Most studies addressing this question have used change detection tasks in which the feature value before the change is highly discriminable from the feature value after the change. This approach assumes that memory noise is negligible, which recent work has shown not to be the case. Here, we investigate VSTM for orientation and color within a noisy-memory framework, using change localization with a variable magnitude of change. A specific consequence of the noise is that it is necessary to model the inference (decision) stage. We find that (a) orientation and color have independent pools of memory resource (consistent with classic results); (b) an irrelevant feature dimension is either encoded but ignored during decision-making, or encoded with low precision and taken into account during decision-making; and (c) total resource available in a given feature dimension is lower in the presence of task-relevant stimuli that are neutral in that feature dimension. We propose a framework in which feature resource comes both in packaged and in targeted form.
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Project description:Visual short-term memory (VSTM) relies on a distributed network including sensory-related, posterior regions of the brain and frontal areas associated with attention and cognitive control. To characterize the fine temporal details of processing within this network, we recorded event-related potentials (ERPs) while human subjects performed a recognition-memory task. The task's difficulty was graded by varying the perceptual similarity between the items held in memory and the probe used to access memory. The evaluation of VSTM's contents against a test stimulus produced clear similarity-dependent differences in ERPs as early as 156 ms after probe onset. Posterior recording sites were the first to reflect the difficulty of the analysis, preceding their frontal counterparts by about 50 ms. Our results suggest an initial feed-forward interaction underlying stimulus-memory comparisons, consistent with the idea that visual areas contribute to temporary storage of visual information for use in ongoing tasks. This study provides a first look into early neural activity underlying the processing of visual information in short-term memory.
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Project description:We measured cortical activity with functional magnetic resonance imaging to probe the involvement of early visual cortex in visual short-term memory and visual attention. In four experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. Early visual cortex exhibited sustained responses throughout the delay when subjects performed attention-demanding tasks, but delay-period activity was not distinguishable from zero when subjects performed a task that required short-term memory. This dissociation reveals different computational mechanisms underlying the two processes.
| S-EPMC2696572 | biostudies-literature