Interplay between memory and executive functions in normal and pathological aging

Healthy older adults and Alzheimer's disease (AD) patients are reported in the literature to be impaired in memory and executive functions. This research investigates the extent of these two abilities in determining pathological aging. Groups of young-old and old-old healthy people (Experiment 1) and individuals with amnestic mild cognitive impairment (a-MCI) and AD (Experiment 2) were administered verbal and visuo-spatial tests graded for memory and/or executive requirements. Results indicate a decline in visuo-spatial tasks requiring memory and executive functions in healthy aging. The a-MCI showed memory deficits similar to those shown by AD, but preserved executive functions. Executive function decline could be the critical feature of dementia.     

Effect of aging on stimulus-reward association learning

The flexible learning of stimulus-reward associations when required by situational context is essential for everyday behavior. Older adults experience a progressive decline in several cognitive functions and show deficiencies in neuropsychological tasks requiring flexible adaptation to external feedback, which could be related to impairments in reward association learning. To study the effect of aging on stimulus-reward association learning 20 young and 20 older adults performed a probabilistic object reversal task (pORT) along with a battery of tests assessing executive functions and general intellectual abilities. The pORT requires learning and reversing associations between actions and their outcomes. Older participants collected fewer points, needed more trials to reach the learning criterion, and completed less blocks successfully compared to young adults. This difference remained statistically significant after correcting for the age effect of other tests assessing executive functions. This suggests that there is an age-related difference in reward association learning as measured using the pORT, which is not closely related to other executive functions with respect to the age effect. In human aging, structural alterations of reward detecting structures and functional changes of the dopaminergic as well as the serotonergic system might contribute to the deficit in reward association learning observed in this study.     

Hippocampal formation lesions produce memory impairment in the rhesus monkey

There is much debate over the role of temporal lobe structures in the ability to learn and retain new information. To further assess the contributions of the hippocampal formation (HF), five rhesus monkeys received stereotactically placed ibotenic acid lesions of this region without involvement of surrounding ventromedial temporal cortices. After surgery, the animals were trained on two recognition memory tasks: the Delayed Non-Match to Sample (DNMS) task, which tests the ability to remember specific trial unique stimuli, and the Delayed Recognition Span Task (DRST), which tests the ability to remember an increasing array of stimuli. Relative to normal control monkeys, those with HF lesions demonstrated significant impairments in both learning and memory stages of the DNMS task. Additionally, the HF group was significantly impaired on spatial, color, and object versions of the DRST. Contrary to suggestions that damage to the entorhinal and parahippocampal cortices is required to produce significant behavioral deficits in the monkey, these results demonstrate that selective damage to the HF is sufficient to produce impairments on tasks involving delayed recognition and memory load. This finding illustrates the importance of the HF in the acquisition and retention of new information.     

Inspection time in non-demented older adults with mild cognitive impairment

The aim of this study was to examine inspection time (IT) performance in older adults with mild cognitive impairment (MCI), who are at higher risk of developing further cognitive decline or dementia. IT is described as an index of speed of informational intake. IT correlates with measures of fluid intelligence and is possibly a marker for the integrity of the cholinergic system of the brain. IT may therefore be useful in aiding the diagnosis of early-stage progressive cognitive impairment. The current study compares IT in 28 people with MCI to 28 age, gender and education-matched controls. The computer-based, visual IT task required participants to discriminate between two visual stimuli that were presented for brief periods. Participants' IT performance was compared to their performance on cognitive and memory tasks. Group comparison showed that participants with MCI performed significantly worse on IT than controls and was not affected by years of education. In combination with other clinical, neuropsychological and biological tests, IT may be a useful assessment tool for improving the identification of older adults at risk for clinically relevant cognitive decline.     

Visuoperceptual impairment in MS patients: nature and possible neural origins.

Failures on visuoperceptual neuropsychological tasks (on neuropsychological tests of visuo-spatial perception or on tests concerning semantic properties of visual objects), may indicate focal deficits of visuoperceptual function, or could be the result of (an)other (peripheral) visual deficit(s), or be the effect of a more general cognitive decline. In multiple sclerosis (MS) patients exhibiting sufficient visual acuity and not showing severe cognitive deterioration, impairment on a comprehensive set of 31 visuoperceptual neuropsychological tasks was compared with spatial resolution deficits (SRD), temporal resolution deficits (TRD) for visual stimuli, abnormal pattern shift visual evoked potential (PSVEP) responses, and failing scores on neuropsychological tasks other than visuoperceptual tasks. Impairment on the visuoperceptual neuropsychological tasks was highly independent from the other abnormal visual and cognitive neurological impairments examined, suggesting that it mostly represented focal deficits. Only TRD in both eyes related to this impairment and this relationship was rather weak. Thus in some MS patients a slowed visual information processing may be one of the combined deficits underlying visuoperceptual neuropsychological task impairment. Given that SRD and TRD were not related to another stage of MS and reflect disturbances of a P (parvocellular channel and ventral stream projections) and M (magnocellular channel and dorsal stream projections) visual-system function respectively, demyelination of a certain M pathway may become a co-determinant of visuoperceptual neuropsychological task impairment more rapidly than damage to a certain P pathway.     

Prospective memory and subjective memory decline: A neuropsychological indicator of memory difficulties in community-dwelling older people

Introduction: Prospective memory difficulties are known to occur in Alzheimer’s disease, and may provide an early indicator of cognitive decline. Older people reporting high levels of subjective memory decline (SMD) but without evidence of cognitive decline on standard neuropsychological tests are increasingly considered at increased risk for Alzheimer’s disease. Therefore, the objective of this study was to investigate whether prospective memory performance is differentially impaired in older people reporting high levels of SMD as compared to a control group. Method: A total of 195 community-dwelling older adults (M_age = 73.48 years) were assessed for self-reported complaints of memory decline and allocated to either a group reporting high levels of SMD (SMD, n = 96) or a healthy control group (HC, n = 99). Groups were assessed on neuropsychological tests, an experimental prospective memory task (focal vs. nonfocal cue conditions), and a naturalistic prospective memory task. Results: The groups did not differ in performance on standard neuropsychological tests of working memory, executive attention, and episodic retrospective memory. Furthermore, on an experimental task of prospective memory (the Supermarket Shopping Trip task), although performance of both groups was better when cues for prospective memory were focal to the ongoing activity (η² = .35), the SMD group were not impaired relative to the control group. On a naturalistic prospective memory task, however, there was a small but significant effect, with the SMD group performing more poorly than the HC group (η² = .02). Conclusions: In older adults with high levels of SMD, naturalistic measures of prospective memory provide an approach to assessing memory performance that can offer a means of investigating the memory complaints of people with SMD. Identifying prospective memory difficulties in SMD also offers a focus for intervention.     

Dyslexic adolescents: evidence of impaired visual and auditory language processing associated with normal lateralization and visual responsivity.

The questions of whether chronically dyslexic adolescent suffer any deficits of simple language stimulus processing or are less left hemisphere dominant than normal reading controls were addressed. The dyslexics were chosen for clarity of their specific reading problem and were older than dyslexics previously studied with lateralizing tests. Tasks administered in Experiment I were unilateral and bilateral tachistoscopic work recognitions and a tachistoscopic recognition report-time task for single lateralized letter stimuli. Experiment II, conducted a year later, readministered these tasks with modifications, and added dichotic digits and motor reaction time-stimulus detection tasks. It was concluded that right handed, chronic dyslexics: (1) possess left hemisphere language specialization; (2) show normal interhemispheric processing delays for single letter stimuli; (3) are, unlike nondyslexis but equally poor-reading Ss, clearly impaired in their efficiency of visual and auditory processing of simple language stimuli; (4) possess clear auditory memory deficits for verbal material; and (5) may possess an additional deficit of left hemisphere visual association area function.     

Social cognition in schizophrenia: similarities and differences of emotional perception from patients with focal frontal lesions

The structural and functional abnormalities of the frontal lobes, the region implicated in social information processing, have been suspected to underlie social cognitive impairments in schizophrenia. However, multiple structures, including the limbic/paralimbic areas that are also important for social cognition, have been reported to be abnormal in schizophrenia. The aim of this study is to investigate the extent to which the frontal lobe dysfunction accounts for social cognitive impairments in schizophrenia by comparing with patients who have focal frontal lobe injuries. Social cognitive abilities, focusing on affective aspects, were examined by an emotion intensity recognition task, which is sensitive to the amygdala function, and the emotion attribution tasks, which rely mainly on the frontal lobe function. Individuals with schizophrenia were impaired on the emotion intensity recognition task as well as on the emotion attribution tasks as compared with healthy subjects. By contrast, the frontal lobe-damaged group was defective in the emotion attribution tasks but not in the emotion intensity recognition task. Our results indicated that social cognitive impairments observed in schizophrenia can be accounted for partly by their frontal lobe pathology. Other aspects of social cognitive impairments could also be associated with the extra-frontal pathology, such as the amygdala.     

Olfactory and gustatory capacities of alcoholic Korsakoff patients

The psychophysical method of magnitude estimation was used to assess the olfactory, gustatory, visual and auditory capacities of alcoholic Korsakoff patients. The Korsakoffs were most impaired in their scaling of olfactory and gustatory stimuli but did evidence some mild impairments on two of the three visual tasks. In contrast, right-hemisphere lesion patients were impaired on all three visual tasks and on an auditory task, but they scaled olfactory and gustatory stimuli in a normal manner. This dissociation indicates that the Korsakoffs difficulties with the chemical senses cannot be attributed to the complexity of the tests.     

The effects of old age and distraction on the assessment of prospective memory in a simulated naturalistic environment

BACKGROUND: The ability to remember to complete future intentions, prospective memory, often begins to fail in old age. The aim of the present study was to examine the sensitivity of a computer-based procedure using naturalistic stimuli to age-related increases in forgetting under conditions of high (increased visual and auditory noise) or low distraction. METHODS: Participants were tested in a virtual shopping precinct constructed from linked photographs, sounds, and video segments. Groups of 32 older and younger persons completed two concurrent memory tasks while moving along the street. In one task, participants were given errands to complete with an accessible checklist, in the other, they were required to remember to respond to three different targets that appeared repeatedly. RESULTS: The results confirmed previous findings that older adults have difficulty remembering future intentions, even on a self-paced task using naturalistic stimuli, and showed that this was accentuated in noisy environments. CONCLUSIONS: Older persons have particular difficulty remembering in noisy environments, and results from testing in the clinic may underestimate the practical memory problems experienced by older adults with mild cognitive impairments. The findings provide encouragement for the construction of computer-generated environments to measure functional deficits in cognition.     

A sensitizing regimen of amphetamine that disrupts attentional set-shifting does not disrupt working or long-term memory

Exposure to an intermittent, escalating dose of amphetamine induces a sensitized state that, both behaviourally and neurochemically, mirrors several features linked to the positive symptoms of schizophrenia. Increasingly it is being realized that cognitive deficits are a core component of schizophrenia; therefore we sought to assess the effects of inducing an amphetamine-sensitized state on memory (working and long-term) and cognitive flexibility, two cognitive domains impaired in schizophrenia. Rats were exposed to a sensitizing regimen of amphetamine (1-5 mg/kg; three times per week for 5 weeks; escalating at 1mg/kg per week) or saline. In experiment 1, animals were tested on an operant delayed non-match to position task (working memory). Experiment 2 used a standard fixed-platform location water maze task (long-term memory), while experiment 3 used a variable-platform location water maze task (long-term memory and working memory). Amphetamine-sensitized animals were not impaired on any of these tasks. In experiment 4, animals were assessed on a strategy selection task in which they were first required to learn to locate a food reward using a particular learning strategy (place or response) then to learn to shift to an alternate learning strategy (response or place). Amphetamine-sensitized animals were not impaired on this task. In the final experiment animals were found to be impaired in performance of the extra-dimensional shift component of an attentional set-shifting task. These results suggest that while amphetamine sensitization does not produce memory impairments similar to those seen in schizophrenia, it does produce strong impairments in set-shifting, suggesting changes in prefrontal function similar to those seen in schizophrenia.     

Deficits in hippocampal‐dependent transfer generalization learning accompany synaptic dysfunction in a mouse model of amyloidosis

Elevated β‐amyloid and impaired synaptic function in hippocampus are among the earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments employed in both humans and animal models, however, are insensitive to this early disease pathology. One critical aspect of hippocampal function is its role in episodic memory, which involves the binding of temporally coincident sensory information (e.g., sights, smells, and sounds) to create a representation of a specific learning epoch. Flexible associations can be formed among these distinct sensory stimuli that enable the “transfer” of new learning across a wide variety of contexts. The current studies employed a mouse analog of an associative “transfer learning” task that has previously been used to identify risk for prodromal AD in humans. The rodent version of the task assesses the transfer of learning about stimulus features relevant to a food reward across a series of compound discrimination problems. The relevant feature that predicts the food reward is unchanged across problems, but an irrelevant feature (i.e., the context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral ibotenic acid lesions of hippocampus were able to discriminate between two stimuli on par with control mice; however, lesioned mice were unable to transfer or apply this learning to new problem configurations. Experiment 2 used the APP_swePS1 mouse model of amyloidosis to show that robust impairments in transfer learning are evident in mice with subtle β‐amyloid‐induced synaptic deficits in the hippocampus. Finally, Experiment 3 confirmed that the same transfer learning impairments observed in APPswePS1 mice were also evident in the Tg‐SwDI mouse, a second model of amyloidosis. Together, these data show that the ability to generalize learned associations to new contexts is disrupted even in the presence of subtle hippocampal dysfunction and suggest that, across species, this aspect of hippocampal‐dependent learning may be useful for early identification of AD‐like pathology. © 2015 Wiley Periodicals, Inc.     

The nature of lexico-semantic processing deficits in mild cognitive impairment

Lexico-semantic impairments in Alzheimer disease (AD) have been attributed to abnormalities in both intentional and automatic access to semantic memory. However, the order in which these impairments appear during the course of the disease is unclear. We sought to answer this question by documenting lexico-semantic impairments in 61 subjects with mild cognitive impairment (MCI), a pre-AD stage, and by comparing them to those of 39 AD and 60 normal elderly (NE) subjects. All subjects were tested with intentional access tasks (picture naming and semantic probes), automatic access tasks (lexical decision and priming), and executive function tasks (Stroop and Stroop-Picture naming). Results indicated that the MCI group was only impaired on tasks of intentional access relative to the AD group who was impaired on both types of tasks. Because most MCI subjects eventually develop AD, these results suggest that intentional access to semantic memory is impaired before automatic access. Further, impairments on the Stroop-Picture naming task but not on the Stroop task, suggest that lexico-semantic impairments in the MCI group may be related to inhibition deficits during semantic search. Findings are discussed in light of executive dysfunctions within the framework of semantic memory theories.     

Trajectories of change in self-reported psychotic-like experiences in childhood and adolescence

Estimates of pre-morbid IQ are widely used to measure the trajectory of cognitive function and decline in people with schizophrenia. This study examined the usefulness of two indices of decline to identify cognitive subtypes in first episode psychosis, and to determine the specificity of non-IQ neuropsychological impairments in this population. Neuropsychological data were collected from 118 first episode psychosis patients and compared to 118 epidemiologically matched controls. The National Adult Reading Test (NART) and the Information subtest of the WAIS-III were compared as indicators of crystallised intelligence or 'pre-morbid IQ'. Measurement of NART minus current full scale IQ (FSIQ) (where 10 points discrepancy is the decline criterion) did not reveal a large group of individuals with 'deteriorating' IQ patterns. Using the Information subtest and the same decline criteria, a 'deteriorating' patient group emerged (36%) but was matched by a larger 'deteriorating' control group (45%). The 'deteriorating' patient group performed at a low IQ level for tasks that loaded highly on performance ability but a relatively high level for tasks measuring verbal skills. Verbal memory discriminated patients from controls better than IQ. Compared to controls, patients showed large selective impairments of verbal episodic memory (effect size, d=1.4) These data suggest that in first episode populations, caution should be exercised in inferring deterioration of IQ from discrepancies between reading-based and other IQ tests. Rather, sub-groups of patients and controls do show greater verbal aptitude in comparison to performance skills. Memory is generally impaired in first episode patients regardless of IQ.     

Procedural learning in Parkinson's disease: intact and impaired cognitive components.

Two experiments were carried out to study procedural learning in Parkinson's disease (PD) patients. In Experiment 1, ten patients and their normal controls participated in a classical mirror reading task and in an inverted reading task where word-stimuli made of non inverted letters had to be processed from right to left (e.g., ygoloruen). In both tasks, reading times for new stimuli were compared to reading times for stimuli that repeated over blocks. Although PD patients and their controls exhibited learning for repeated words in both tasks, PD patients did not respond faster with practice for new words in the inverted reading task. In Experiment 2, PD patients and their controls were presented with an original dot counting task in which participants were asked to process a horizontal series of black and white dots from right to left and to indicate whether a dot that had been designated by a number at the beginning of each trial was black or white. Results showed that PD patients, in contrast to controls, did not exhibit learning in this task. Results are discussed in terms of the cognitive components involved in these tasks. It is suggested that PD patients are impaired in the acquisition of a right-to-left visual scanning skill that could be studied directly in Experiment 2.     

Closing-in behavior in mild cognitive impairment: an executive deficit

This study explored Closing-in behavior (CIB), the tendency in figure copying to draw very close to or on top of the model, in mild cognitive impairment (MCI). The files of 154 people diagnosed with MCI were reviewed and CIB was identified in 21% of cases. Two approaches were used to explore CIB. First, we capitalized on the diverse cognitive profiles within MCI, subdividing the overall sample into people with and without memory deficits. The frequency of CIB was significantly higher in multidomain non-amnestic MCI than in multidomain amnestic MCI, suggesting that CIB is not associated with specific memory impairment. Second, we assessed the cognitive correlates of CIB, by selecting patients with MCI who completed a battery of executive, visuo-constructional and memory tasks. Sub-groups of patients with and without CIB showed a similar overall severity of cognitive decline and comparable performance in visuo-constructional and memory tasks, but those with CIB were slightly but significantly more impaired on executive function tasks. The study provides evidence against memory-based accounts of CIB, and supports recent suggestions that executive impairments are the dominant cognitive correlate of this clinical sign.     

Serial order short-term memory capacities and specific language impairment: No evidence for a causal association

This study re-explored the nature of verbal short-term memory (STM) deficits in children with specific language impairment (SLI), by distinguishing item and serial order STM processes. Recent studies have shown serial order STM capacity to be a critical determinant of language development, relative to item STM. In Experiment 1, 12 children with SLI, 12 age-matched children and 12 language-matched children were administered serial order recognition and reconstruction tasks. Experiment 2 assessed implicit serial learning abilities via a Hebb learning task. The SLI group showed impaired performance for the serial order reconstruction and recognition tasks, relative to language-matched and/or age-matched control groups. However, normal serial position effects were observed in all SLI children in the serial order reconstruction task, suggesting normal coding of serial position information. Similarly, performance on the Hebb serial learning task was at chronological age appropriate levels. Experiment 3 showed that the group differences observed for the serial order STM tasks in Experiment 1 disappeared when the SLI group was compared to a mental age-matched control group. Experiment 4 showed similar performance levels in the SLI group and the mental age-matched control group for a nonword recognition task assessing item STM capacities. This study shows that children with SLI have no specific impairments for serial order and item STM components but that poorer general cognitive efficiency is related to functional limitations in verbal STM tasks. The data are in line with limited information processing accounts of SLI.     

Contributions of the prefrontal cortex and basal ganglia to set shifting

Impairments of set shifting have been associated with damage to both the prefrontal cortex (PFC) and to the basal ganglia. The purpose of these experiments was to determine whether damage to the PFC was associated with shifting impairments per se or whether any switching deficits could be attributed to a reduction of working memory capacity. In contrast, shifting impairments were expected for Parkinson patients regardless of memory load, given that these patients seem to have no cognitive deficits other than when having to shift set. To vary working memory demands, a cue to the relevant dimension (letter or shape) in an odd-man-out task was presented or withheld. Pathology to prefrontal areas associated with normal aging was not linked to shifting deficits when working memory load was reduced in a comparison of older and younger adults (Experiment 1). In contrast, set-shifting abilities were still impaired for stroke patients with prefrontal damage regardless of working memory demands (Experiment 2). Parkinson patients were relatively unimpaired on this task (Experiment 2), but began to display shifting deficits when response competition was present in the display (Experiment 3).     

Behavioral characterization of mild cognitive impairment

Results from recent investigations of behavioral and genetic outcomes in older people with mild cognitive impairment (MCI) have been inconsistent. These conflicting results may be attributed to between-study differences in the diagnostic systems employed, as well as the use of unreliable neuropsychological measures. We investigated behavioral and genetic outcomes in older people classified as having MCI according to novel criterion that required evidence of cognitive impairment on three consecutive neurological/neuropsychological assessments. One hundred and seventy four healthy older people were evaluated semi-annually for 12 months. Of these, 23 subjects were rated as having MCI on three consecutive assessments and were compared to 23 matched control subjects. Subjects rated as impaired on one or two of the three semi-annual assessments were also identified. MCI and matched control groups were compared on a range of behavioral measures. The prevalence of the Apolipoprotein E4 (ApoE4) allele was determined in all groups, and estimates of anxiety and depressive symptomatology were obtained. Subjective cognitive complaints were also assessed. Many subjects were classified as impaired on one or two assessments, however relatively few (n = 23) recorded consistent cognitive deficits. The most severe impairment observed in MCI subjects was on a test of pattern-location associative learning, however MCI subjects did not have insight into this impairment. The prevalence of the ApoE4 allele was not different between matched control and MCI groups. These results indicate that individuals with MCI can be differentiated from healthy older people and older people with transient cognitive impairments, but that such differentiation requires serial assessment of cognitive function.     

Age-related loss in attention-based modulation of tactile stimuli at early stages of somatosensory processing

Normal aging has been linked to impairments in gating of irrelevant sensory information and neural markers of diminished cognitive processing. Whilst much of the research in this area has focussed on visual and auditory modalities it is unclear to what degree these findings apply to somatosensation. Therefore we investigated how age impacts early event-related potentials (ERPs) arising from relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we hypothesised that older adults would demonstrate reduced attention-based modulation of tactile ERPs generated at early stages of cortical somatosensory processing. In accord with previous research we also expected to observe diminished P300 responses to attended targets and behavioural deficits. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only (as instructed) with comparisons between two age groups: (1) Young adults (age range 20-39) and (2) Older adults (age range 62-89). ERP amplitudes for the P50, N70, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at several electrodes (C4, CP4, CP3 and FC4). The P300 in response to attended target stimuli was measured at CPZ. There was no effect of attention on the P50 and N70 however the P100, N140 and LLP were modulated with attention. In both age groups the P100 and LLP were more positive during trials where the stimuli were attended to, whilst the N140 was enhanced for non-attended stimuli. Comparisons between groups revealed a reduction in P100 attention-based modulation for the older adults versus the young adults. This effect was due to a loss of suppression of the non-attended stimuli in older subjects. Moreover, the P300 was both slower and reduced in peak amplitude for older subjects in response to attended targets. Finally, older adults demonstrated impaired performance in terms of both reduced target detection accuracy and in reporting more false positives. Overall, present results reveal a deficit in suppressing irrelevant tactile information during an attention-demanding task which possibly relates to reduced markers of performance. Such a loss of inhibitory function is consistent with age-related change associated with a decline in executive control via prefrontal regions.