Remote Memory Deficits Research Articles

Desipramine reverses remote memory deficits by activating calmodulin-CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome.

Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability. UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role of UTX in cognitive function remains unclear. Currently, no targeted therapies are available for KS. This study aimed to investigate how UTX regulates cognition, to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment. We generated UTX conditional knockout mice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation. UTX-knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine. Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS.

Exploring mechanisms that affect retrograde memory for public events in amnestic mild cognitive impairment: A longitudinal update.

Here, we examined mechanisms that affect retrograde memory in amnestic mild cognitive impairment (a-MCI) as a function of longitudinal clinical outcome. 8 a-MCI who converted to Alzheimer's dementia (AD) during the subsequent 3-year follow-up (converter a-MCI) and 10 a-MCI who remained clinically stable during the same period (stable a-MCI) were compared at the baseline evaluation (i.e., when they were diagnosed as a-MCI) using a remote memory questionnaire for public events that allows disentangling the differential contribution of storage and retrieval mechanisms to performance accuracy. Results suggest that deficits in remote memory are primarily explained by impaired retrieval abilities in stable a-MCI and by impaired storage in converter-to-AD a-MCI. This distinction between retrograde amnesia due to defective trace utilisation in stable a-MCI and trace storage in converter a-MCI is consistent with the temporal unfolding of declining anterograde memory over the course of disease progression to AD.

Remote Memory in Epilepsy: Assessment, Impairment, and Implications Regarding Hippocampal Function.

Studies of epilepsy patients provide insight into the neuroscience of human memory. Patients with remote memory deficits may learn new information but have difficulty recalling events from years past. The processes underlying remote memory impairment are unclear and likely result from the interaction of multiple factors, including hippocampal dysfunction. The hippocampus likely has a continued role in remote semantic and episodic memory storage over time, and patients with mesial temporal lobe epilepsy (TLE) are at particular risk for deficits. Studies have focused on lateralization of remote memory, often with greater impairment in left TLE, which may relate to verbal task demands. Remote memory testing is restricted by methodological limitations. As a result, deficits have been difficult to measure. This review of remote memory focuses on evidence for its underlying neurobiology, theoretical implications for hippocampal function, and methodological difficulties that complicate testing in epilepsy patients.

Prenatal fluoxetine impairs non-hippocampal but not hippocampal memory in adult male rat offspring

Fluoxetine is often prescribed to treat depression during pregnancy. Rodent studies have shown that fluoxetine exposure during early development can induce persistent changes in the emotional behavior of the offspring. However, the effects of prenatal fluoxetine on memory have not been elucidated. This study evaluates the memory of adult male offspring from rat dams orally administered with a clinically relevant dose of 0.7 mg/kg fluoxetine from 9 weeks before pregnancy to 1 week before delivery. Hippocampal-dependent (Morris Water Maze, MWM) and non-hippocampal-dependent (Novel Object Recognition, NOR) memory paradigms were assessed. Anxiety- and depressive-like symptoms were also evaluated using the Open Field Test, Tail Suspension Test and Sucrose Preference Test. Male rats exposed to fluoxetine during gestation displayed NOR memory impairments during adulthood, as well as increased anxiety- and depressive-like symptoms. In the MWM, the offspring of fluoxetine-treated dams did not show learning deficits. However, a retention impairment was found on remote memory, 15 days after the end of training. Molecular analyses showed increased expression of NMDA subunit NR2B, and a decrease in NR2A-to- NR2B ratio in the temporal cortex, but not in the hippocampus, suggesting changes in NMDA receptor composition. These results suggest that in utero exposure to fluoxetine induces detrimental effects on non-hippocampal memory and in remote retention of hippocampal-dependent memory, which is believed to be stored in the temporal cortex, possibly due to changes in cortical NMDA receptor subunit stoichiometry. The present results warrant the need for studies on potential remote memory deficits in human offspring exposed to fluoxetine in utero.

Lost or unavailable? Exploring mechanisms that affect retrograde memory in mild cognitive impairment and Alzheimer's disease patients.

Retrograde amnesia has been largely documented in patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD). However, it is still not clear whether ineffectiveness in recalling past acquired information reflects loss of individual memory traces or failure to access specific stored traces. We aimed to disentangle the differential contribution of storage and retrieval processes to the pattern of retrograde amnesia in these patients. This issue was investigated in 18 a-MCI and 19 AD patients who were compared to 20 healthy controls. A novel questionnaire about public events was used; it consisted of two procedures (i.e., a free recall test and a true/false recognition test). Crucial differences emerged in the way the two groups of patients performed the experimental tasks. In fact, although both a-MCI and AD patients showed a similar pattern of impairment on the free recall test, a-MCI patients were able to normalise their performance on the recognition test, thus overcoming their deficits at the time of recall. Conversely, AD patients showed both reduced free recall ability and diminished sensitivity to benefit from recognition in recalling public events. Our findings suggest that the memory processes underlying RA were different for a-MCI and AD. Deficits in remote memory are prevalently explained by impaired retrieval abilities in a-MCI and by impaired storage in AD. This distinction between retrograde amnesia due to defective trace utilisation in a-MCI and trace storage in AD is consistent with the temporal unfolding of declining anterograde memory over the course of disease progression to AD.

Cognitive Impairments After Clipping of Ruptured Anterior Circulation Aneurysms

The cognitive impairments after treatment of ruptured aneurysms have often been underestimated. This study sought to assess their prevalence and analyze various associated factors. Patients who were operated on for ruptured anterior circulation aneurysms and discharged with a Glasgow Outcome Scale score of 4-5 were studied at 3 months for various cognitive impairments. Continuous scales of memory (recent, remote, verbal, visual, and overall memory), verbal fluency (phonemic and category fluency), and others were studied in relation to various factors. Univariate and multivariate analyses were performed using SPSS version21. A total of 87 patients were included in our study. Phonemic fluency was the most affected, noted in 66% of patients. Although 56% had some memory-related impairments, 13 (15%) and 6 (7%) had moderate and severe deficits in recent memory and 19 (22%) and 12 (14%) had moderate and severe deficits in remote memory, respectively. Patients operated on for anterior cerebral artery (ACA) aneurysms had significantly greater impairments in recent (34% vs. 8%) and remote memory (43% vs. 28%) compared with the rest, both in univariate (P= 0.01 and 0.002, respectively) and multivariate analyses (P= 0.01 and 0.03, respectively). ACA-related aneurysms also had significantly greater independent impairments in phonemic fluency (P= 0.04), compared with others. The clinical grade had a significant independent impact only on remote memory (P= 0.01). Cognitive impairments are frequent after treatment of ruptured anterior circulation aneurysms. Impairments in recent memory, remote memory, and phonemic fluency are significantly greater after treatment of ACA-related aneurysms, compared with others, independent of other factors.

PREVALENCE AND FACTORS INFLEUENCING DRIVING CESSATION IN EARLY-ONSET ALZHEIMER’S DISEASE

Driving impairment studies in Alzheimer's disease (AD) have focused mostly on older adults. Lesser is known about driving impairment in those with early onset AD (EOAD) (aged less than 65 years), which is vital for them to work, take their children to school and for their leisure activities. We aimed to evaluate the prevalence of driving cessation in EOAD referred to Younger Person's Memory Service (YPMS), a specialist service for young onset dementia and to establish factors influencing driving cessation in EOAD patients. The cross sectional study cohort consists of 64 EOAD patients who were former or current car-drivers (mean age 59.45 (±4.5) years, 39.1% females), who attended YPMS at the Leicestershire Partnership NHS Trust, East Midlands of England during 2000–2010. Reasons for driving cessation were assessed with the patients' caregivers. All patients were assessed for cognition, functional abilities and behaviour symptoms following a semi-structured interview. Cognitive functioning was determined by Mini-Mental State Examination (MMSE and the Cambridge cognitive Examination (CAMCOG), Bristol activities of daily living (BADL) for daily functioning, and behaviour by the Neuropsychiatric Inventory (NPI). 24 patients with EOAD stopped driving (37.5%) either voluntarily or after given the advice by clinicians or Driver and Vehicle Licensing Agency. Women were more likely to stop driving by themselves (52%). EOAD patients who ceased driving had lower scores on Mini Mental State Examination (p=0.010) and total CAMCOG (p=0.015). They also had significantly more deficits in remote memory (p=0.02), learning memory (p=0.036) and total praxis (p=0.009). Female gender and increasing impairment in cognitive abilities raise the probability of driving cessation in EOAD. These factors need to be considered when assessing driving abilities and counselling patient and families.

A Case of Wernicke-Korsakoff Syndrome Treated 1 Year After the Onset of Symptoms.

A Case of Wernicke-Korsakoff Syndrome Treated 1 Year After the Onset of Symptoms.

015 Remote memory deficits in transient epileptic amnesia

AimsTransient epileptic amnesia (TEA) is a recently recognised form of temporal lobe epilepsy in which sufferers often complain of irretrievable loss of remote memories. We aimed to answer the following...

Remote memory deficits in transient epileptic amnesia

Transient epileptic amnesia is a form of temporal lobe epilepsy in which sufferers often complain of irretrievable loss of remote memories. We used a broad range of memory tests to clarify the extent and nature of the remote memory deficits in patients with transient epileptic amnesia. Performance on standard tests of anterograde memory was normal. In contrast, there was a severe impairment of memory for autobiographical events extending across the entire lifespan, providing evidence for the occurrence of 'focal retrograde amnesia' in transient epileptic amnesia. There was a milder impairment of personal semantic memory, most pronounced for midlife years. There were limited deficits of public semantic memory for recent decades. These results may reflect subtle structural pathology in the medial temporal lobes or the effects of the propagation of epileptiform activity through the network of brain regions responsible for long-term memory, or a combination of these two mechanisms.

Transient News Events Test: Feasibility in assessment of post-temporal lobectomy remote memory deficits

Although anterograde memory deficits are well documented in patients with epilepsy, the extent to which remote memory deficits occur is less clear. This is due in part to a lack of reliable methods for assessment. The present study examined the feasibility of using the Transient News Events Test (TNET) to assess remote memory in subjects status post anterior temporal lobectomy (ATL) for the treatment of refractory seizures. Results indicated significantly poorer performance of the patient group compared to healthy controls. The decrement in performance within the patient group was evident only for items from more recent time periods. Reasons for an apparent stability of the most remote memories with ATL and implications regarding hippocampal function are reviewed. In conclusion, the TNET provides a feasible method for assessment of remote memory function in patients with epilepsy, with decrements in performance noted in comparison to a healthy control group in this retrospective study.

Mild cognitive impairment does entail retrograde amnesia for public events

In this study memory for public events was evaluated in 15 amnesic mild cognitive impairment (aMCI) patients, whose clinical diagnosis was refined through a stringent selection procedure. A total of 9 patients were longitudinally reassessed over an 18-month period. About half of the participants were impaired at baseline and nearly 80% at the end of the 18-month follow-up. Moreover, retrograde memory declined significantly over time. Evidence of a pathological Ribot-type temporal gradient was found in about half of the aMCI patients. This is the first report of a remote memory deficit in aMCI. It highlights amnesia for public events as a frequent accompaniment of this condition. The findings tie in with the hypothesized role of the hippocampal complex in long-term memory.

Functional retrograde amnesia: A multiple case study

Functional retrograde amnesia (RA) is a rare pathology and has been rarely studied in detail across different patients. We extensively examined five functional RA patients and compared their neuropsychological profile including anterograde and retrograde memory performance, executive functions, emotional processing, and formally assessed psychiatric symptoms. Across patients, neuropsychological deficits beyond RA were most consistently seen in executive functions and attention suggesting that these dysfunctions contribute to the remote memory deficit. In a majority of the patients, problems in social cognition and emotional behaviour were reflected in Theory of Mind deficits and accompanying psychiatric symptoms. Aberrances in a measure of social desirability were detected, pointing to repressive tendencies in three out of the five patients. Future studies of functional RA patients may investigate more specifically which frontal-lobe associated (dys-) functions contribute to the memory retrieval deficit. Moreover, studying more closely the interaction between social cognition, repressive personality style and memory inhibition in this disease seems worthwhile pursuing.

New circuits for old memories: the role of the neocortex in consolidation.

Studies of learning and memory have provided a great deal of evidence implicating hippocampal mechanisms in the initial storage of facts and events. However, until recently, there were few hints as to how and where this information was permanently stored. A recent series of rodent molecular and cellular cognition studies provide compelling evidence for the involvement of specific neocortical regions in the storage of information initially processed in the hippocampus. Areas of the prefrontal cortex, including the anterior cingulate and prelimbic cortices, and the temporal cortex show robust increases in activity specifically following remote memory retrieval. Importantly, damage to or inactivation of these areas produces selective remote memory deficits. Additionally, transgenic studies provide glimpses into the molecular and cellular mechanisms underlying cortical memory consolidation. The studies reviewed here represent the first exciting steps toward the understanding of the molecular, cellular, and systems mechanisms of how the brain stores our oldest and perhaps most defining memories.

Cognitive Deficits and Polymorphism of Apolipoprotein E in Alzheimer’s Disease

The aim of this study was to test the relationship between apolipoprotein E (ApoE) genotypes and patterns of cognitive deficits in Alzheimer’s disease (AD). All subjects were diagnosed as probable AD patients on the basis of the DSM-IV and NINCDS-ADRDA criteria. Each subject was examined for (1) ApoE genotype, (2) general level of mental activity (Global Deterioration Scale and Mini-Mental State Examination) and (3) cognitive functions by means of a battery of neuropsychological tests. On the basis of ApoE genotype, patients were subdivided into two groups: the first group consisted of patients with at least one Ε4 allele (Ε4+ group), while the second one consisted of patients without the Ε4 allele (Ε4– group). Our results showed that several cognitive processes depended on the ApoE genotype. In early stages of AD, patients from the Ε4+ group had greater deficits in delayed recall of new information. On the other hand, working memory appeared to be more impaired in the Ε4– group of patients. Independent of the genotype, both groups showed similar impairment of learning ability without, however, deficits in remote memory.

Differential Mechanisms of Impairment of Remote Memory in Alzheimer’s and Frontotemporal Dementia

This paper describes retrograde memory performances of 12 Alzheimer’s disease (AD) patients and 12 frontotemporal dementia (FTD) patients. First of all, we observed that FTD and AD patients did not differ for language tests (verbal fluency tests and oral denomination 80), for semantic memory tests, for logical memory test and Benton visual memory test and differed for anterograde verbal memory and frontal tests. Concerning retrograde memory, there was no difference between AD and FTD patients in retrograde memory scores (autobiographical memory interview, Crovitz’s task, French public events interview battery) and both FTD and AD patients exhibited a retrieval deficit in their remote memory. We observed that the mechanisms of remote memory deficit was different in FTD and in AD patients. We observed no classical paradigm of Ribot for FTD patient’s remote informations, and they appeared to have lost of access to memories and executive difficulties. In AD, the results indicated these patients’ ability to learn new information and to search semantic memory failed.

Retrograde amnesia in patients with diencephalic,temporal lobe or frontal lesions

Patients with focal diencephalic, temporal lobe, or frontal lobe lesions were examinedon various measures of remote memory. Korsakoff patients showed a severe impairment with acharacteristic temporal gradient, whereas two patients with focal diencephalic damage (andanterograde amnesia) were virtually unimpaired on remote memory measures. Patients withfrontal lobe pathology were severely impaired in the recall of autobiographical incidents andfamous news events. Patients with temporal lobe pathology showed severe impairment but arelatively flat temporal gradient, largely attributable to herpes encephalitis patients. Fromrecognition and cued recall tasks, it is argued that there is an important retrieval component tothe remote memory deficit across all the lesion groups. In general, the pattern of performance bythe frontal lobe and temporal lobe groups was closely similar, and there was no evidence of anymajor access⧸storage difference between them. However, laterality comparisons across thesegroups indicated that the right temporal and frontal lobe regions may make a greater contributionto the retrieval of past episodic (incident and event) memories, whereas the left temporal regionis more closely involved in the lexical-semantic labelling of remote memories.

Retrograde amnesia for medical and other knowledge in a physician with Alzheimer's disease

Previous studies of patients with Alzheimer's disease (AD) demonstrate that these patients exhibit marked loss of premorbldly acquired knowledge with a tendency for relative preservation of information from the distant past. Few studies have examined the multiple components of remote memory in the same patients and no study has measured memory for old (1.e. obsolete) and recent aspects of any patient's professional knowledge. We studied two retired physicians: an internist (A) with probable AD, and a general practitioner (P) with Parkinson's disease. Both were symptomatic for about 5 years. A displayed marked and general deficits in remote memory, and on almost all tests showed relatively better memory for more recent information. P performed normally on all remote memory tests. In AD, memory for premorbid knowledge appears to deteriorate rapidly over the course of the disease; more recent memories may be partially protected because they are more often rehearsed.

The Relationship between Retrograde and Anterograde Amnesia in Patients with Typical Global Amnesia

An extensive battery of tests of anterograde amnesia and remote memory was given to ten amnesics with lesions either to the medial temporal lobes of the diencephalon. These showed that the patients had anterograde amnesia with deficits in verbal and non-verbal recall and recognition, but preservation of word stem completion and intelligence. Mild impairments on executive tests and digit span performance were largely caused by the poor performance of the Korsakoff patients. The amnesics also showed remote memory deficits for personal and public domain information, and temporal gradients were observed for some of the tests. These deficits probably arose because the patients' anterograde amnesia was more severe than their retrograde amnesia even for the recent pre-morbid past. They were more impaired in the recall of details about famous names than in their ability to recognize such names. There was also a suggestion that performance on anterograde tests did not relate strongly to that on tests of retrograde amnesia of the remote pre-morbid past. However, this effect was less apparent with memory for personal information when the format and the information tapped were matched on pre- and post-morbid tests.

Serotonin as a developmental signal

Fluoxetine is often prescribed to treat depression during pregnancy. Rodent studies have shown that fluoxetine exposure during early development can induce persistent changes in the emotional behavior of the offspring. However, the effects of prenatal fluoxetine on memory have not been elucidated. This study evaluates the memory of adult male offspring from rat dams orally administered with a clinically relevant dose of 0.7 mg/kg fluoxetine from 9 weeks before pregnancy to 1 week before delivery. Hippocampal-dependent (Morris Water Maze, MWM) and non-hippocampal-dependent (Novel Object Recognition, NOR) memory paradigms were assessed. Anxiety- and depressive-like symptoms were also evaluated using the Open Field Test, Tail Suspension Test and Sucrose Preference Test. Male rats exposed to fluoxetine during gestation displayed NOR memory impairments during adulthood, as well as increased anxiety- and depressive-like symptoms. In the MWM, the offspring of fluoxetine-treated dams did not show learning deficits. However, a retention impairment was found on remote memory, 15 days after the end of training. Molecular analyses showed increased expression of NMDA subunit NR2B, and a decrease in NR2A-to- NR2B ratio in the temporal cortex, but not in the hippocampus, suggesting changes in NMDA receptor composition. These results suggest that in utero exposure to fluoxetine induces detrimental effects on non-hippocampal memory and in remote retention of hippocampal-dependent memory, which is believed to be stored in the temporal cortex, possibly due to changes in cortical NMDA receptor subunit stoichiometry. The present results warrant the need for studies on potential remote memory deficits in human offspring exposed to fluoxetine in utero.