Vividness of visual imagery questionnaire scores and their relationship to visual short-term memory performance.

Mechanisms underlying visual imagery, the ability to create vivid mental representations of a scene in the absence of sensory input, remain to be fully understood. Some previous studies have proposed that visual imagery might be related to visual short-term memory (STM), with a common mechanism involving retention of visual information over short periods of time. Other observations have shown a strong relationship between visual imagery and functional activity in the hippocampus and primary visual cortex, both regions also associated with visual STM. Here we examined the relationship of visual imagery to STM and hippocampal and primary visual cortex volumes, first in a large sample of healthy people across a large age range (N = 229 behavioural data; N = 56 MRI data in older participants) and then in patients with Alzheimer's disease and Parkinson's disease (N = 19 in each group compared to 19 age-matched healthy controls). We used a variant of the "What was where?" visual object-location binding task to assess the quality of remembered information over short delays. In healthy people, no evidence of a relationship between the vividness of visual imagery and any visual STM performance parameter was found. However, there was a significant positive correlation between visual imagery and the volumes of the hippocampus and primary visual cortex. Although visual STM performance was significantly impaired in patients with Alzheimer's disease, their vividness of visual imagery scores were comparable to those of age-matched elderly controls and patients with Parkinson's disease. Despite hippocampal volumes also being reduced in Alzheimer's patients, there appeared to be no impact on their self-reported visual imagery. In conclusion, visual imagery was not significantly related to visual STM performance, either in healthy controls or Alzheimer's or Parkinson's disease but it was related to hippocampal and visual cortex volume in healthy people.

Superior short-term memory in APOE ε2 carriers across the age range.

The Apolipoprotein-E (APOE) gene is now known to be associated with individual differences in cognitive health in ageing. However, while the APOE ε4 allele confers significantly increased risk of developing Alzheimer's disease (AD), the APOE ε2 allele is hypothesized to be protective against the development of AD. This is in line with neuroimaging and pathological findings associated with ε2 APOE allele, which go in the opposite direction to those observed in AD-related pathology. However, the precise impact of this allele on cognition remains inconclusive, with some small-cohort studies raising the possibility of an advantageous memory performance in these individuals. Here, we tested short-term memory (STM) performance in a large cohort of individuals, 300 of which were ε2/ε3 carriers. Their performance was compared to 554 ε3/ε3 carriers. We included participants from a wide age range spanning young, middle-aged and elderly adults. All of them performed a STM task that has previously been shown to be sensitive to subtle changes in memory in various patient and at-risk cohorts. Individuals carrying the APOE-ε2 allele exhibited a significant memory advantage, regardless of STM task difficulty and across all ages. The observed memory advantage was present across the age range, suggestive of a phenotypical effect of this allele on cognition, possibly independent of any effects of this genetic allele that occur later life in these individuals.

Different patterns of short-term memory deficit in Alzheimer's disease, Parkinson's disease and subjective cognitive impairment.

It has recently been proposed that short-term memory (STM) binding deficits might be an important feature of Alzheimer's disease (AD), providing a potential avenue for earlier detection of this disorder. By contrast, work in Parkinson's disease (PD), using different tasks, has suggested that the STM impairment in this condition is characterised by increased random guessing, possibly due to fluctuating attention. In the present study, to establish whether a misbinding impairment is present in sporadic late-onset AD (LOAD) and increased guessing is a feature of PD, we compared the performance of these patient groups to two control populations: healthy age-matched controls and individuals with subjective cognitive impairment (SCI) with comparable recruitment history as patients. All participants performed a sensitive task of STM that required high resolution retention of object-location bindings. This paradigm also enabled us to explore the underlying sources of error contributing to impaired STM in patients with LOAD and PD using computational modelling of response error. Patients with LOAD performed significantly worse than other groups on this task. Importantly their impaired memory was associated with increased misbinding errors. This was in contrast to patients with PD who made significantly more guessing responses. These findings therefore provide additional support for the presence of two doubly dissociable signatures of STM deficit in AD and PD, with binding impairment in AD and increased random guessing characterising the STM deficit in PD. The task used to measure memory precision here provides an easy-to-administer assessment of STM that is sensitive to the different types of deficit in AD and PD and hence has the potential to inform clinical practice.

Short-term memory advantage for brief durations in human APOE ε4 carriers.

The Apolipoprotein-E (APOE) ε4 gene allele, the highest known genetic risk factor for Alzheimer's disease, has paradoxically been well preserved in the human population. One possible explanation offered by evolutionary biology for survival of deleterious genes is antagonistic pleiotropy. This theory proposes that such genetic variants might confer an advantage, even earlier in life when humans are also reproductively fit. The results of some small-cohort studies have raised the possibility of such a pleiotropic effect for the ε4 allele in short-term memory (STM) but the findings have been inconsistent. Here, we tested STM performance in a large cohort of individuals (N = 1277); nine hundred and fifty-nine of which included carrier and non-carriers of the APOE ε4 gene, those at highest risk of developing Alzheimer's disease. We first confirm that this task is sensitive to subtle deterioration in memory performance across ageing. Importantly, individuals carrying the APOE ε4 gene actually exhibited a significant memory advantage across all ages, specifically for brief retention periods but crucially not for longer durations. Together, these findings present the strongest evidence to date for a gene having an antagonistic pleiotropy effect on human cognitive function across a wide age range, and hence provide an explanation for the survival of the APOE ε4 allele in the gene pool.