Episodic Memory Impairment Research Articles

National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome.

To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.

Evaluating cognitive profiles of patients undergoing clinical amyloid-PET imaging.

Episodic memory impairment and brain amyloid-beta are two of the main hallmarks of Alzheimer’s Disease. In the clinical setting, these are often evaluated through neuropsychological testing and amyloid PET imaging, respectively. The use of amyloid PET in clinical practice is only indicated in patients with substantial diagnostic uncertainty due to atypical clinical presentation, multiple comorbidities and/or early age of onset. The relationship between amyloid-beta and cognition has been previously investigated, but no study has examined how neuropsychological features relate to the presence of amyloid pathology in the clinical population that meets the appropriate use criteria for amyloid PET imaging. In this study, we evaluated a clinical cohort of patients (n = 107) who presented at the Imperial Memory Clinic and were referred for clinical amyloid PET and neuropsychological assessment as part of their diagnostic workup. We compared the cognitive performance of amyloid-positive patients (Aβ-pos, n = 47) with that of stable amyloid-negative (stableAβ-neg, n = 26) and progressive amyloid-negative (progAβ-neg, n = 34) patients. The amyloid-positive group performed significantly worse than both amyloid-negative groups in the visuospatial and working memory domains. Episodic memory performance, however, effectively differentiated the amyloid-positive group from the stable but not the progressive amyloid-negative group. On affective questionnaires, the stable amyloid-negative group reported significantly higher levels of depression than the amyloid-positive group. In our clinical cohort, visuospatial dysfunction and working memory impairment were better indicators of amyloid positivity than episodic memory dysfunction. These findings highlight the limited value of isolated cognitive scores in patients with atypical clinical presentation, comorbidities and/or early age of onset.

Computational support, not primacy, distinguishes compensatory memory reorganization in epilepsy.

Temporal lobe epilepsy is associated with impairment in episodic memory. A substantial subgroup, however, is able to maintain adequate memory despite temporal lobe pathology. Missing from prior work in cognitive reorganization is a direct comparison of temporal lobe epilepsy patients with intact status with those who are memory impaired. Little is known about the regional activations, functional connectivities and/or network reconfigurations that implement changes in primary computations or support functions that drive adaptive plasticity and compensated memory. We utilized task functional MRI on 54 unilateral temporal lobe epilepsy patients and 24 matched healthy controls during the performance of a paired-associate memory task to address three questions: (i) which regions implement paired-associate memory in temporal lobe epilepsy, and do they vary as a function of good versus poor performance, (ii) is there unique functional connectivity present during memory encoding that accounts for intact status by preservation of primary memory computations or the supportive computations that allow for intact memory responses and (iii) what features during memory encoding are most distinctive: is it the magnitude and location of regional activations, or the presence of enhanced functional connections to key structures such as the hippocampus? The study revealed non-dominant hemisphere regions (right posterior temporal regions) involving both increased regional activity and increased modulatory communication with the hippocampi as most important to intact memory in left temporal lobe epilepsy compared to impaired status. The profile involved areas that are neither contralateral homologues to left hemisphere memory areas, nor regions traditionally considered computationally primary for episodic memory. None of these areas of increased activation or functional connectivity were associated with advantaged memory in healthy controls. Our emphasis on different performance levels yielded insight into two forms of cognitive reorganization: computational primacy, where left temporal lobe epilepsy showed little change relative to healthy controls, and computational support where intact left temporal lobe epilepsy patients showed adaptive abnormalities. The analyses isolated the unique regional activations and mediating functional connectivity that implements truly compensatory reorganization in left temporal lobe epilepsy. The results provided a new perspective on memory deficits by making clear that they arise not just from the knockout of a functional hub, but from the failure to instantiate a complex set of reorganization responses. Such responses provided the computational support to ensure successful memory. We demonstrated that by keeping track of performance levels, we can increase understanding of adaptive brain responses and neuroplasticity in epilepsy.

Self-awareness in Transient Global Amnesia: distinguishing the effects of transient memory disorder vs. pre-existing vulnerability factors

ABSTRACT Numerous evidences suggest the existence of relationships between the impairment of episodic memory, acute stress exposure and variations in self-awareness (SA). Here, we examined 27 patients presenting transient global amnesia (TGA), a clinical condition which combines episodic amnesia and high anxiety, thanks to state and trait questionnaires of SA. We observed variation of SA depending on the stage of TGA (acute, recovery and follow-up). We also found preexisting differences in patient’s awareness of their own image when the precipitating event was physical, encouraging us to give more consideration to the social determinants of stress in physiological cascade of TGA.

Temporal Cognitive and Brain Changes in Korsakoff Syndrome.

To investigate cognitive and brain changes in patients with Korsakoff syndrome (KS) over months and up to 10 years after the diagnosis. Two groups of 8 patients with KS underwent neuropsychological, motor, and neuroimaging investigations, including structural MRI and 18F-fluorodeoxyglucose-PET. The KSC group, recruited at Caen University Hospital, was examined early after the KS diagnosis (KSC-T1) and 1 year later (KSC-T2). The KSR group, recruited at nursing home at Roubaix, was evaluated 10 years after the diagnosis. Longitudinal comparisons in KSC explored short-term changes, while cross-sectional comparisons between KSC-T1 and KSR informed about long-term changes. No cognitive, motor, or brain deterioration occurred over time in patients with KS. There was no clear improvement either, with only modest recovery in the frontocerebellar circuit. Compared to the norms, KSC-T1 had severe episodic memory impairments, ataxia, and some executive dysfunctions. They also presented widespread atrophy and hypometabolism as well as cerebellar hypermetabolism compared to 44 healthy matched controls. Episodic memory remained significantly impaired in KSC-T2 and KSR. Contrary to KSC at T1 and T2, KSR had preserved inhibition abilities. Atrophy was similar but less extended in KSC-T2 and even more limited in KSR. At all times, the thalamus, hypothalamus, and fornix remained severely atrophied. Hypometabolism was still widespread in KSC-T2 and KSR, notably affecting the diencephalon. Cerebellar metabolism decreased over time and normalized in KSR, whereas motor dysfunction persisted. In KS, structural and metabolic alterations of the Papez circuit persisted over time, in accordance with the irreversible nature of amnesia. There was neither significant recovery as observed in patients with alcohol use disorder nor progressive decline as in neurodegenerative diseases.

Different patterns of gray matter atrophy in behavioral variant frontotemporal dementia with and without episodic memory impairment.

Differentiating patients with behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) is important as these two conditions have distinct treatment and prognosis. Using episodic impairment and medial temporal lobe atrophy as a tool to make this distinction has been debatable in the recent literature, as some patients with bvFTD can also have episodic memory impairment and medial temporal lobe atrophy early in the disease. To compare brain atrophy patterns of patients with bvFTD with and without episodic memory impairment to that of patients with AD. We analyzed 19 patients with bvFTD, 21 with AD and 21 controls, matched by age, sex, and years of education. They underwent brain MRI and the memory test from the Brief Cognitive Battery (BCB) to assess episodic memory. We then categorized the bvFTD group into amnestic (BCB delayed recall score <7) and non-amnestic. The amnestic bvFTD group (n=8) had significant gray matter atrophy in the left parahippocampal gyrus, right cingulate and precuneus regions compared with the nonamnestic group. Compared with AD, amnestic bvFTD had more atrophy in the left fusiform cortex, left insula, left inferior temporal gyrus and right temporal pole, whereas patients with AD had more atrophy in the left hippocampus, left frontal pole and left angular gyrus. There is a group of amnestic bvFTD patients with episodic memory dysfunction and significant atrophy in medial temporal structures, which poses a challenge in considering only these features when differentiating bvFTD from AD clinically.

A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms.

Alzheimer's disease (AD) is the commonest cause of dementia, characterized by the clinical presentation of progressive anterograde episodic memory impairment. However, atypical presentation of patients is increasingly recognized. These atypical AD include logopenic aphasia, behavioural variant AD, posterior cortical atrophy, and corticobasal syndrome. These atypical AD are more common in patients with young onset AD before the age of 65 years old. Since medical needs (including the behavioural and psychological symptoms of dementia) of atypical AD patients could be different from typical AD patients, it is important for clinicians to be aware of these atypical forms of AD. In addition, disease modifying treatment may be available in the future. This review aims at providing an update on various important subtypes of atypical AD including behavioural and psychological symptoms.

Working memory training in normal and pathological ageing: neurocognitive gains and their impact on daily-living activities.

Working memory is one of the cognitive functions that is the most sensitive to the effects of normal and pathological ageing. In older individuals with mild cognitive impairments, working memory deficits are frequent and can precede episodic memory impairments, in addition to having a strong prognostic value of evolution toward an Alzheimer-type dementia. Due to its involvement in numerous cognitive and cognitive-motor tasks, working memory is called upon in a wide range of daily activities. An impaired working memory therefore increases the risk of loss of autonomy. In this review, we present different working memory training programmes. We show how these training programmes are associated with specific effects, and near and far transfer effects on other cognitive functions in older adults without cognitive impairment or with mild cognitive impairment, as well as in patients with dementia. We show that the benefits are confirmed by neuronal modifications, suggesting an improvement in the neuronal efficiency of the processes that are trained or related to them. Finally, we consider the central question of the impact of the cognitive gains made by working memory training on activities of daily living.

Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ

IntroductionTo identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis. MethodsIn this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments. ResultsLHC-RHC (F3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ2(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment. ConclusionWe used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.

The public health burden of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is the most common respiratory disorder of sleep. The vast majority (>80%) of adults with moderate to severe OSA remain undiagnosed. The economic costs associated with OSA are substantial for both the individual and society as a whole; expenses are likely to be underestimated given that the disease remains undiagnosed in such a large percentage of individuals. The economic burden of motor vehicle collisions related to OSA alone is significant; it is estimated that 810,000 collisions and 1400 fatalities from car crashes in the United States were attributable to sleep apnea in 2000. The many health consequences of OSA include daytime sleepiness, reduced quality of life, decreased learning skills, and importantly, neurocognitive impairments that include impaired episodic memory, executive function, attention and visuospatial cognitive functions. Untreated OSA leads to numerous medical problems such as cardiovascular diseases that can potentially increase healthcare utilization. Untreated patients with sleep apnea consume a disproportionate amount of healthcare resources, expenditures that decrease after treatment. The gold-standard management of OSA remains treatment with CPAP (Continuous Positive Airway Pressure), which is effective in eliminating sleep fragmentation and preserving nocturnal oxygenation, thereby improving daytime sleepiness and quality of life. However, its impacts in reversing neurocognitive function are still uncertain. A significant impediment to CPAP effectiveness is low adherence rates (ranges from 50% to 75%). It is commonly accepted that CPAP improves excessive drowsiness; hence meliorates attention, and accumulating data suggest that CPAP improves a variety of other outcomes such as the risk of motor vehicle crashes.

Episodic Memory–Related Imaging Features as Valuable Biomarkers for the Diagnosis of Alzheimer’s Disease: A Multicenter Study Based on Machine Learning

BackgroundIndividualized and reliable biomarkers are crucial for diagnosing Alzheimer’s disease (AD). However, lack of accessibility and neurobiological correlation are the main obstacles to their clinical application. Machine learning algorithms can effectively identify personalized biomarkers based on the prominent symptoms of AD. MethodsEpisodic memory–related magnetic resonance imaging (MRI) features of 143 patients with amnesic mild cognitive impairment (MCI) were identified using a multivariate relevance vector regression algorithm. The support vector machine classification model was constructed using these MRI features and verified in 2 independent datasets (N = 994). The neurobiological basis was also investigated based on cognitive assessments, neuropathologic biomarkers of cerebrospinal fluid, and positron emission tomography images of amyloid-β plaques. ResultsThe combination of gray matter volume and amplitude of low-frequency fluctuation MRI features accurately predicted episodic memory impairment in individual patients with amnesic MCI (r = 0.638) when measured using an episodic memory assessment panel. The MRI features that contributed to episodic memory prediction were primarily distributed across the default mode network and limbic network. The classification model based on these features distinguished patients with AD from normal control subjects with more than 86% accuracy. Furthermore, most identified episodic memory–related regions showed significantly different amyloid-β positron emission tomography measurements among the AD, MCI, and normal control groups. Moreover, the classification outputs significantly correlated with cognitive assessment scores and cerebrospinal fluid pathological biomarkers' levels in the MCI and AD groups. ConclusionsNeuroimaging features can reflect individual episodic memory function and serve as potential diagnostic biomarkers of AD.

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury.

Memory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injury patients we examined whether: (i) impairments in memory encoding are associated with abnormal brain activation in these networks; (ii) whether changes in this brain activity predict subsequent memory retrieval; and (iii) whether abnormal white matter integrity underpinning functional networks is associated with impaired subsequent memory. Thirty-five patients with moderate-severe traumatic brain injury aged 23-65 years (74% males) in the post-acute/chronic phase after injury and 16 healthy control subjects underwent functional MRI during performance of an abstract image memory encoding task. Diffusion tensor imaging was used to assess structural abnormalities across patient groups compared to 28 age-matched healthy controls. Successful memory encoding across all participants was associated with activation of the dorsal attention network, the ventral visual stream and medial temporal lobes. Decreased activation was seen in the default mode network. Patients with preserved episodic memory demonstrated increased activation in areas of the dorsal attention network. Patients with impaired memory showed increased left anterior prefrontal activity. White matter microstructure underpinning connectivity between core nodes of the encoding networks was significantly reduced in patients with memory impairment. Our results show for the first time that patients with impaired episodic memory show abnormal activation of key nodes within the dorsal attention network and regions regulating default mode network activity during encoding. Successful encoding was associated with an opposite direction of signal change between patients with and without memory impairment, suggesting that memory encoding mechanisms could be fundamentally altered in this population. We demonstrate a clear relationship between functional networks activated during encoding and underlying abnormalities within the structural connectome in patients with memory impairment. We suggest that encoding failures in this group are likely due to failed control of goal-directed attentional resources.

Longitudinal clinical and neuroanatomical correlates of memory impairment in motor neuron disease

Memory impairment in motor neuron disease (MND) is still an underrecognized feature and has traditionally been attributed to executive dysfunction. Here, we investigate the rate of memory impairment in a longitudinal cohort of MND patients, its relationship to other cognitive functions and the underlying neuroanatomical correlates. 142 patients with MND and 99 healthy controls (HC) underwent comprehensive neuropsychological testing and structural MRI at 3T up to four times over a period of 18 months. Linear-mixed effects models were fitted to identify changes at baseline and over time in episodic memory function (learning, immediate and delayed recall, recognition), composed cognitive scores (memory, verbal fluency, executive function), and memory-related structural brain regions (hippocampus, entorhinal cortex, parahippocampal gyrus). Associations between episodic memory performance and volumetric or cortical thickness changes of these regions were computed using Pearson's r. Learning, immediate and delayed recall, as well as recognition performance were significantly reduced in MND when compared to controls at baseline. Performances in these subtests improved over time although MND showed less improvement than controls. This relationship did not change when only “classical” ALS patients were considered. Patients with MND showed thinning of the right parahippocampal gyrus (PhG) in comparison to controls that was progressing over time. Bilateral hippocampal atrophy was observed in MND patients with memory impairment after splitting the group according to their overall episodic memory performance, with the right hippocampus shrinking over time. In MND patients, the bilateral hippocampal atrophy was associated with impairment in learning, recall, and recognition at baseline. In contrast, left PhG thinning was associated with a poorer learning performance. These results show that episodic memory impairment in MND is a frequent cognitive dysfunction. Since deficits are not clearly declining with disease course, an early involvement of this cognitive domain in the disease seems probable. The memory performance-dependent atrophy of the hippocampus and PhG provide evidence for a widespread involvement of these non-motor cortical areas in disease pathology.

Age-Cohort Differences in Longitudinal Associations Between the Rate of Internet Use and Memory Functioning

Cross-sectional analyses of internet use patterns among older adults find that the rate of internet use is less with greater physical and memory difficulties. It is not clear, however, how age-cohorts differ in their internet use as physical and memory difficulties increase over time. In addition to factors such as increasing accessibility (cost) and social influences, the expansion and cognitive complexity of functions performed by the internet-enabled devices over time could influence internet use patterns. In this study, we investigate how the association between internet use and episodic memory difficulties over time varies between cohorts. We analyzed longitudinal data from the Health and Retirement Study (N = 15,703 in 2002; Aged 51 and older) between years 2002-2016 using mixed effects logistic regression models. Immediate and delayed word recall measures were used to assess episodic memory. Rate of internet use in the sample increased from 30% in 2002 to 53% in 2016. Rate of internet use among younger age groups was significantly higher in the baseline year. Younger age groups also showed a significantly higher rate of increase in internet use over time. In general, internet use decreased with episodic memory impairment. In addition to these effects, the effect of episodic memory on the rate of increase in internet use over time is lower in younger cohorts. These results indicate that younger cohorts of older adults are more likely to maintain internet use as they continue to age and therefore could better utilize technology for communication, social interactions and health interventions.

Aberrant Maturation of the Uncinate Fasciculus Follows Exposure to Unpredictable Patterns of Maternal Signals.

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother-child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key component of the medial temporal lobe-prefrontal cortex circuit. Infant exposure to unpredictable maternal sensory signals was assessed at 6 and 12 months. Using high angular resolution diffusion imaging, we quantified the integrity of the uncinate fasciculus using generalized fractional anisotropy (GFA). Higher maternal unpredictability during infancy presaged greater uncinate fasciculus GFA in children 9-11 years of age (n = 69, 29 female). In contrast to the uncinate, GFA of a second corticolimbic projection, the hippocampal cingulum, was not associated with maternal unpredictability. Addressing the overall functional significance of the uncinate and cingulum relationships, we found that the resulting imbalance of medial temporal lobe-prefrontal cortex connectivity partially mediated the association between unpredictable maternal sensory signals and impaired episodic memory function. These results suggest that unbalanced maturation of corticolimbic circuits is a mechanism by which early unpredictable sensory signals may impact cognition later in life.SIGNIFICANCE STATEMENT Our prior work across species demonstrated that unpredictable patterns of maternal care are associated with compromised memory function. However, the neurobiological mechanisms by which this occurs in humans remain unknown. Here, we identify an association of exposure to unpredictable patterns of maternal sensory signals with the integrity of corticolimbic circuits involved in emotion and cognition using state-of-the-art diffusion imaging techniques and analyses. We find that exposure to early unpredictability is associated with higher integrity of the uncinate fasciculus with no effect on a second corticolimbic pathway, the cingulum. The resulting imbalance of corticolimbic circuit development is a novel mediator of the association between unpredictable patterns of maternal care and poorer episodic memory.

Biomarkers of memory variability in traumatic brain injury.

Traumatic brain injury is a leading cause of cognitive disability and is often associated with significant impairment in episodic memory. In traumatic brain injury survivors, as in healthy controls, there is marked variability between individuals in memory ability. Using recordings from indwelling electrodes, we characterized and compared the oscillatory biomarkers of mnemonic variability in two cohorts of epilepsy patients: a group with a history of moderate-to-severe traumatic brain injury (n = 37) and a group of controls without traumatic brain injury (n = 111) closely matched for demographics and electrode coverage. Analysis of these recordings demonstrated that increased high-frequency power and decreased theta power across a broad set of brain regions mark periods of successful memory formation in both groups. As features in a logistic-regression classifier, spectral power biomarkers effectively predicted recall probability, with little difference between traumatic brain injury patients and controls. The two groups also displayed similar patterns of theta-frequency connectivity during successful encoding periods. These biomarkers of successful memory, highly conserved between traumatic brain injury patients and controls, could serve as the basis for novel therapies that target disordered memory across diverse forms of neurological disease.

Caspr 2 antibody associated disease–An unusual presentation

Introduction: Antibodies to Voltage Gated Potassium Channels (VGKC) are directed against Leucine-rich Glioma- Inactivated1 (LGI1) and Contactin Associated Protein like 2 (Caspr2). Common presentations of Caspr2 antibody associated diseases include limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. New clinical phenotypes are being considered to the spectrum of Caspr2 antibody associated disease. Here we report a case of Caspr2 antibody associated disease with an unusual clinical presentation. Case Report: 40 year old male presented with distal symmetrical sensorimotor neuropathy of 4 months duration. Subsequently he had developed neurobehavioral symptoms in the form of irritability, episodic memory impairment and seizures. After medical evaluation he was diagnosed to have anti Caspr2 antibody associated disease. Patient showed improvement with an immunosuppressive therapy, but had recurrence of autoimmune encephalitis 1 month later. Along with that, he had also developed right vocal cord palsy, for which no other cause was identified. Patient improved with second line immunosuppressive therapy. He had no further recurrence and is under follow up. Keywords: Voltage gated potassium channels, Leucine-rich Glioma-inactivated 1, Contactin associated protein, Limbic encephalitis, Neuromyotonia.

Language and memory: an investigation of the relationship between autobiographical memory recall and narrative production of semantic and episodic information

ABSTRACT Background: The production of autobiographical narratives requires linguistic structures and the ability to access and generate both semantic information and episodic details of personal events. Aims: This study investigated autobiographical narratives produced by individuals with established semantic memory impairments (semantic variant primary progressive aphasia; svPPA) or episodic memory impairments (amnestic mild cognitive impairment; aMCI) in order to investigate whether different categories of memory impairment would manifest different linguistic deficits. Methods & Procedures: We used the Autobiographical Interview and Quantitative Production Analysis methods to investigate linguistic production during autobiographical recall. Additional investigations compared the production of present and past tense inflections in order to look for morpho-syntactic differences in the sets of episodic and semantic information. Outcomes and Results: The results showed that individuals with svPPA produced fewer well-formed sentences when producing episodic details and produced fewer past tense inflections when producing semantic details in comparison to healthy controls. The aMCI group produced fewer episodic utterances but produced a larger number of words in the set of semantic details, in comparison to healthy controls. Conclusions: It is possible that specific demands related to the type of message being conveyed, or high cognitive load during retrieval of episodic information may affect the narration process. Difficulty in the retrieval of episodic information is likely related to reduced production of episodic utterances in individuals with aMCI and may be related to deficits in linguistic production in svPPA. We propose that the results in the set of semantic details are connected to previous findings relating to semantic memory and deficits in discourse coherence in both groups.

Cognitive profiles in amyloid‐PET‐eligible patients: A retrospective study

AbstractBackgroundThe early cognitive profile of Alzheimer’s Disease (AD) is typically characterised by predominant impairment in episodic memory, reflecting medial temporal lobe dysfunction. However, little is known about the cognitive profile associated with AD pathology in those patients who meet Appropriate Use Criteria (AUC, Johnson et al., 2013) for Amyloid PET Imaging (API). In this group, AD pathology is frequently associated with an atypical clinical course or presentation. Here, we systematically evaluate the cognitive profiles of AUC‐meeting patients in a real‐world clinical setting, combining the information provided by the neuropsychological assessment with the results of Amyloid PET Imaging.MethodFrom a larger sample of 396 patients who underwent Amyloid PET at the Imperial Memory Centre between December 2013 and June 2019, we included those individuals who also had at least one formal neuropsychological assessment (minimum of 4 tests) within 18 months of API (n=124). Both these were solely conducted for clinical purposes, and API was requested after multidisciplinary team discussion. Cognitive measures in amyloid positive (Aβ+) and negative (Aβ‐) patients were compared using non‐parametric tests.ResultsNeuropsychological assessment preceded Amyloid PET Imaging in most cases, for both amyloid‐positive (n=51, mean age 67.24±9.32 years, 58.8% female) and amyloid‐negative (n=73, mean age 67.9±9.64 years, 41.1% female) groups. Cognitive performance in the amyloid‐positive group was significantly worse in 6 of the 14 cognitive measures taken into account: visuo‐spatial functioning, executive functioning, working memory, verbal learning, verbal delayed recall, and confrontation naming (Figure 1). Verbal learning, verbal delayed recall and confrontation naming were the most frequently impaired measures in the amyloid‐positive group, with around 50% of patients performing below 2 standard deviations. Notably, self‐reported symptoms of depression were significantly higher in the amyloid‐negative (7.3±4.38) than in the amyloid‐positive group (4.68±3.7) (p=.002) (Figure 2).ConclusionsIn a sample of patients attending a tertiary Behavioural Neurology clinic, neuropsychological evaluation revealed worse performance in positive API across a range of domains, particularly verbal memory and confrontation naming, with higher rates of symptoms of depression being reported more frequently in the amyloid negative group.

Sex differences in the relation of mixed TDP‐43 and AD pathologies to risk of dementia and cognitive decline

AbstractBackgroundIt is well‐established that TDP‐43 pathology (also known as LATE) is commonly observed in the brains of older persons, is often mixed with AD pathology, and increases the risk of impairment in episodic memory and Alzheimer’s dementia. It is not known whether there are sex differences in the relation of mixed TDP‐43 and AD pathology with Alzheimer’s dementia and decline in memory.MethodWe included 1,406 autopsied participants who initially enrolled without dementia from three ongoing epidemiologic longitudinal clinical‐pathologic studies of aging: Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study. Participants underwent annual clinical evaluations for diagnosis of Alzheimer’s dementia, including the administration of seven cognitive tests to create summary measures of episodic memory. Systematic uniform neuropathologic examination quantified TDP‐43, AD, and other age‐related pathologies. Persons were categorized into 4 groups; those with no AD or TDP, ‘pure’ TDP, ‘pure’ AD, and mixed AD/TDP. We conducted mixed effects and logistic regression models controlling for age at death, sex, race, and education with cognitive decline and dementia as outcomes, respectively.ResultsIn fully adjusted models that controlled for demographics and other age‐related pathologies, compared to older persons without AD or TDP‐43 pathology, those having either or both pathologies had faster decline in episodic memory. Further, there was a sex difference such that the association of mixed AD/TDP‐43 on episodic memory decline was stronger in women than in men (b = 0.040, SE = 0.018, p = 0.022). Similarly, compared to those with no AD or TDP, having ‘pure’ TDP (OR = 3.261), ‘pure’ AD (OR = 4.176), or mixed AD/TDP‐43 (OR = 10.342) increased the odds of dementia (all p’s &lt;0.001). However, “pure” TDP‐43 pathology increased the odds of dementia more strongly in men than in women (OR = 1.392, 95% CI: 0.555, 0.012), in fully adjusted models.ConclusionThe results suggest sex differences in the effects of mixed AD/TDP‐43 pathology and ‘pure’ TDP pathology on risk of Alzheimer’s dementia and decline in episodic memory. These effects are independent of demographics and other age‐related pathologies.