Retrieval Deficits Research Articles

Pause Characteristics by Utterance Position in Patients with Primary Progressive Aphasia Subtypes

Objectives: Primary progressive aphasia (PPA) is a neurodegenerative disease characterized by prominent language impairments within the first two years of onset. PPA is clinically categorized into three subtypes: semantic variant (svPPA), logopenic variant (lvPPA), and non-fluent/agrammatic variant (nfvPPA). Pauses that occur during speech production in primary progressive aphasia (PPA) can serve as simple and reliable biomarkers for subtype classification and early diagnosis of PPA. This study aimed to investigate the characteristics of pauses in PPA subtypes during a picture description task. Methods: The study included a total of 60 participants: 9 with semantic variant (svPPA), 19 with logopenic variant (lvPPA), 11 with nonfluent variant (nfvPPA), and 21 healthy controls. After transcribing the participants’ speech, their pause durations were measured using the acoustic analysis program, Praat. Pauses were categorized as inter-utterance, intra-utterance, inter-word, and intra-word pauses. Results: Among the three types of PPA, the nfvPPA manifested slower speech rates and longer pauses between utterances compared to the svPPA and lvPPA. Furthermore, the lvPPA showed longer pauses between words within utterances compared to the svPPA. Conclusion: This study found that speech rate and pause durations differed by subtype, with the nfvPPA showing effortful speech due to increased articulatory complexity, which is attributed to neuroanatomical insult. The lvPPA may utilize pauses to compensate for word retrieval deficits during speech production. This study is significant as it provides pause characteristics in speech across different PPA subtypes via acoustic analysis.

Disrupted brain networks underlying high-fidelity memory retrieval in subjective cognitive decline: A task-based fMRI study.

Subjective cognitive decline (SCD) is linked to memory complaints and disruptions in certain brain regions identified by molecular imaging and resting-state functional magnetic resonance imaging studies. However, it remains unclear how these regions interact to contribute to both subjective and potential objective memory issues in SCD. To address this gap, task-based imaging studies are essential. The Mnemonic Similarity Task assessed high-fidelity retrieval meanwhile MRI data measured group differences in activation and functional connectivity (FC) (calculated by generalized psychophysiological Interaction) between SCD individuals and normal controls. Worse high-fidelity retrieval in SCD was associated with hypoactivation in the hippocampus, hyperactivation in the control network (CN), and reduced FC between the hippocampus and CN. The angular gyrus (AG) partially drives this disconnection. This study confirms objective cognitive deficits in SCD and highlights the AG's failure to integrate, addressing a gap in the literature that has primarily focused on the hippocampus and CN. Objective high-fidelity retrieval deficits detected in older adults with SCD. Dysfunctional neural activations within retrieval networks impair memory accuracy. Reduced task-based FC drives high-fidelity retrieval deficits. The SCD-related disruption of integrative function partly explains such deficits. Future studies may benefit from inspections on obstruction in cognitive process.

Teasing apart time reference-related encoding and retrieval deficits in aphasia: evidence from Greek, Russian, Italian and English

ABSTRACT Background Persons with aphasia (PWAs) are often impaired in time reference/tense production. It has been suggested that this impairment is due to encoding or/and retrieval deficits. However, to the best of our knowledge, no experimental design that enables teasing apart selective encoding and retrieval deficits has been proposed thus far. Aims This study aims at disentangling time reference-related encoding deficits from time reference-related retrieval deficits in PWAs. Methods & procedures Two sentence completion tasks tapping production of time reference and subject-verb agreement (control condition) were administered to eight Greek-speaking PWAs, eight Russian-speaking PWAs, six Italian-speaking PWAs, seven English-speaking PWAs and four groups of language-, age- and education-matched healthy controls. Task 1 tapped encoding and retrieval processes to a similar extent. Task 2 predominantly tapped retrieval processes. Comparisons between each PWA and the corresponding control group, as well as within-participant comparisons were performed. Outcomes & results All four control groups performed at ceiling. Twenty-eight out of 29 PWAs were impaired in time reference in at least one of the two completion tasks, and all but three PWAs were impaired in production of subject-verb agreement in at least one of the two tasks. In all language groups, there were PWAs exhibiting between-task dissociations. A double dissociation emerged in the time reference condition, as some Greek-, Russian- and English-speaking PWAs performed better on Task 1 than on Task 2, whereas other Greek- and Italian-speaking PWAs performed worse on Task 1 than on Task 2. In the agreement condition, in each language group, there were PWAs performing better on Task 1 than on Task 2. However, none PWA exhibited the opposite pattern. Based on the results, we identified both PWAs with selective time reference-related encoding deficits and PWAs with selective time reference-related retrieval deficits. Conclusions The present experimental design provides a sound basis for teasing apart selective time reference-related encoding deficits and time reference-related retrieval deficits.

Dopamine D1 receptors activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 neonatal schizophrenia model

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7–11 postnatal days, PND). We evaluated synaptic plasticity late-LTP and spatial memory consolidation in early adolescence and young adulthood using extracellular field recordings in acute hippocampal slices and the Barnes maze task. Next, we examined D1 receptor (D1R) activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of dopamine D1R ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.

B - 91 Characterizing Memory Profiles of Movement Disorders: the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Recognition Subtests

Abstract Objective This study explores the utility of novel recognition memory composites integrating recently developed recognition subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Duff et al., 2021) in characterizing memory profiles across Mild Cognitive Impairment (MCI) and Normal Cognitive Study (NCS) groups in patients with movement disorders. Methods Twenty patients with movement disorders (M = 69.4 years, SD = 6.3) were administered the RBANS including additional Story and Figure Recognition subtests as part of a comprehensive neuropsychological evaluation at an academic medical center. Samples were stratified by MCI (n = 15) and NCS (n = 5) groups based on clinician diagnoses. Z-score based composites were created for individual recognition measures (total, hits, false positives, and discriminability indices, d’) and “Total Delayed Recall” memory composites across list, story, and figure subtests. Results Mann–Whitney U test analyses revealed significant differences between MCI and NCS groups on Story recognition d’ performance, U = 9.50, p = <0.05. Within the MCI group, a paired samples t-test revealed significantly worse performance on recognition d’ compared to “Total Delayed Recall” (M = 1.63, SD = 2.22); t(14) = 2.84, p = <0.05. Conclusions Greater impairment in recognition discriminability compared to delayed recall suggests the involvement of memory processes that extend beyond retrieval deficits typically observed in movement disorders characterized by subcortical/frontosubcortical profiles. Further investigations are warranted in establishing implications of recognition memory composites in differentiating among MCI subtypes and neurodegenerative disease progression within movement disorder populations, as findings may have been influenced by unequal variances between groups.

Algorithm-defined memory impairment in older American Indians: The Strong Heart Study.

Assessment of cognition in American Indians poses challenges, including barriers to healthcare, unvalidated clinical standards, and confounding social determinants of health. Alternative strategies for case identification include algorithmic methods, which can outperform clinical judgment in some circumstances. Algorithmic methods can be maximized using single-domain tests with multiple-serial trial tasks, such as the California Verbal Learning Test II-Short Form (CVLT-SF). We collected CVLT-SF and detailed clinical data, including dementia gold standard by consensus adjudication, in 818 American Indians aged 65-95 in 2010-2013 and repeated in 403 returning participants in 2017-2019 (mean follow-up 6.7 years, range: 4-9). Our algorithm categorized CVLT-SF scores into four memory deficit categories: none, encoding, storage, and retrieval. At Visit 1, 75.4% had no memory deficit, 15.6% encoding deficit, 3.5% storage deficit, and 5.5% retrieval deficit. At Visit 2, comparable percentages were 68.7%, 10.6%, 6.5%, and 14.2% (respectively). The majority with any deficit at Visit 1-especially encoding-were lost to follow-up by Visit 2. Most with deficits at Visit 2 were newly categorized from those previously intact. The performance of our memory algorithm, compared with adjudication for dementia, was moderately good: correct classification 69%, sensitivity 51%, and specificity 91%. These descriptive findings encompass a novel contribution in defining memory impairment among American Indians from a single cognitive test. However, more work is needed to improve the sensitivity of this algorithm and maximize its utility for case identification over conventional methods. Altogether, these data provide an important step toward better cognitive characterization and dementia care for an understudied, underserved population. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Repetitive Transcranial Magnetic Stimulation for Action Naming in Aphasia Rehabilitation: A Systematic Review and Meta-Analysis.

Anomia, characterized by difficulty in word retrieval, particularly action verbs, poses a significant challenge in post-stroke aphasia. Repetitive transcranial magnetic stimulation (rTMS) has gained attention for language processing investigations and interventions. This systematic review explores the potential of rTMS as a modality to address action-verb deficits in post-stroke aphasia. We searched MEDLINE via PubMed, CINAHL via Ebsco and Web of Science in February 2024 for English articles (1996-2024). Eligible studies involved post-stroke aphasia action naming rehabilitation with rTMS. In some of these studies, rTMS was combined with speech-language therapy. In total, 10 studies were included in this systematic review. These articles highlight the potential of rTMS in improving verb retrieval deficits. While significant improvements may not be evident, notable progress both before and after intervention is observed in this review. However, it also underscores the need for further research to enhance language recovery for individuals with post-stroke aphasia.

A modified neural circuit framework for semantic memory retrieval with implications for circuit modulation to treat verbal retrieval deficits.

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart etal., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits.

Repetitive traumatic brain injury-induced complement C1-related inflammation impairs long-term hippocampal neurogenesis.

JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/β-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

Neuropsychological profiles comparison between Multiple Sclerosis patients and Multiple Sclerosis patients with overlapping features of systemic lupus erythematosus

AimMultiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) are autoimmune disorders that may lead to cognitive impairment. This study aimed to compare the neuropsychological profiles of patients with MS, and MS and coexisting SLE features. MethodsWe included a total of 90 participants, divided into 3 groups: 30 patients with clinically definite relapsing remitting MS, 30 with coexisting MS and incomplete SLE (overlap group) and 30 healthy controls (HC). All participants underwent neuropsychological assessment with the Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Selective Reminding Test (SRT). ResultsBoth groups scored lower on the MoCA compared to the HC (p < .001). The overlap group showed the lowest performance on the SDMT and PASAT compared to the other two groups (p < .01), while the MS group scored similarly to the HC in the PASAT (p > .05). Regarding the learning rate and long-term recall, the overlap group had lower scores compared to both the MS and HC (p < .001), but it outperformed both groups in the retention efficacy score (p < .001). The MS group did not differ significantly from the HC in these memory domains (p > .05). ConclusionThe overlap group exhibited a broader range of impairments, including slower processing speed, decreased working memory, reduced learning rate, and long-term retrieval deficits. Their retention ability remained intact. The coexistence of MS with SLE pathology had additive impacts on cognitive function.

Auditory naming is impaired in posterior cortical atrophy and early-onset Alzheimer's disease.

Visual naming ability reflects semantic memory retrieval and is a hallmark deficit of Alzheimer's disease (AD). Naming impairment is most prominently observed in the late-onset amnestic and logopenic variant Primary Progressive Aphasia (lvPPA) syndromes. However, little is known about how other patients across the atypical AD syndromic spectrum perform on tests of auditory naming, particularly those with primary visuospatial deficits (Posterior Cortical Atrophy; PCA) and early onset (EOAD) syndromes. Auditory naming tests may be of particular relevance to more accurately measuring anomia in PCA syndrome and in others with visual perceptual deficits. Forty-six patients with biomarker-confirmed AD (16 PCA, 12 lvPPA, 18 multi-domain EOAD), at the stage of mild cognitive impairment or mild dementia, were administered the Auditory Naming Test (ANT). Performance differences between groups were evaluated using one-way ANOVA and post-hoc t-tests. Correlation analyses were used to examine ANT performance in relation to measures of working memory and word retrieval to elucidate cognitive mechanisms underlying word retrieval deficits. Whole-cortex general linear models were generated to determine the relationship between ANT performance and cortical atrophy. Based on published cutoffs, out of a total possible score of 50 on the ANT, 56% of PCA patients (mean score = 45.3), 83% of EOAD patients (mean = 39.2), and 83% of lvPPA patients (mean = 29.8) were impaired. Total uncued ANT performance differed across groups, with lvPPA performing most poorly, followed by EOAD, and then PCA. ANT performance was still impaired in lvPPA and EOAD after cuing, while performance in PCA patients improved to the normal range with phonemic cues. ANT performance was also directly correlated with measures of verbal fluency and working memory, and was associated with cortical atrophy in a circumscribed semantic language network. Auditory confrontation naming is impaired across the syndromic spectrum of AD including in PCA and EOAD, and is likely related to auditory-verbal working memory and verbal fluency which represent the nexus of language and executive functions. The left-lateralized semantic language network was implicated in ANT performance. Auditory naming, in the absence of a visual perceptual demand, may be particularly sensitive to measuring naming deficits in PCA.

The nature of memory impairment in multiple sclerosis: understanding different patterns over the course of the disease.

Memory deficit is one of the most common and severe cognitive impairments in patients with multiple sclerosis and can greatly affect their quality of life. However, there is currently no agreement as to the nature of memory deficit in multiple sclerosis. This cross-sectional study, carried out at the Dr. Josep Trueta and Santa Caterina hospitals in Girona (Spain), was designed to determine the semiology of verbal memory deficit in the different stages of the disease. To this end, a modification of Rey's verbal auditory test was created by introducing two recognition trials between the five learning trials, thus monitoring what happens in terms of acquisition versus the retrieval of information during the learning phase. Linear regression models were used to evaluate verbal episodic memory performance between-groups adjusting results by age, sex, educational level, and the presence of anxiety and/or depressive symptoms. 133 patients with multiple sclerosis, clinically isolated syndrome, and radiologically isolated syndrome and 55 healthy controls aged 18-65 years were assessed. It was observed that the memory processes of multiple sclerosis patients worsen with the progression of the disease. In this respect, patients in pre-diagnostic phases (radiologically isolated syndrome and clinically isolated syndrome) show no differences in verbal episodic memory compared to the healthy controls. Patients in the inflammatory stage (relapsing-remitting multiple sclerosis) show a previously learned information retrieval deficit, while patients in progressive stages (secondary progressive multiple sclerosis and primary progressive multiple sclerosis) do not even correctly acquire information. These results provide significant information to assist in understanding the nature of memory deficits in multiple sclerosis over the course of the disease. These results are discussed in terms of possible cognitive rehabilitation strategies depending on the evolutive stage and are related to neuropathological mechanisms involved in the progression of the disease.

Ameliorative Effects of FMRFamide on 3,4-Methylenedioxyl-Methamphetamine /Tramadol-Induced Neurodegeneration in the Hippocampus

Objective: Tramadol and 3,4-methylenedioxy-methamphetamine (MDMA) use over an extended period is linked to deficits in memory encoding and retrieval. We aimed to determine the neurotoxic effects of co-administration of MDMA and tramadol (TRAM) on hippocampal function and investigate the potential of FMRFamide in attenuating resulting alterations in the Wistar rat model. Methods: Thirty adult male Wistar rats were grouped into six (n=5): Control, FMRFamide, TRAM, MDMA, TRAM+MDMA, and TRAM + MDMA + FMRFamide groups. The opiates were administered orally at 20mg/kg each, while 2mg/kg of FMRFamide was administered intraperitoneally for 12 days using normal saline as a vehicle. The Barnes and Morris water mazes were used to evaluate spatial learning and memory functions, followed by H&amp;E staining, and immunohistochemical staining for glial fibrillary acid protein (GFAP). Results: The opiates significantly increased total latencies in the Barnes Maze test, indicating that short- and long-term memory functions were impaired. Also, high levels of escape latency were observed following MDMA administration, suggesting that MDMA reduced the spatial navigation ability of the animals. These discrepancies were noticeably extreme in animals that received co-administration of opiates. However, FMRFamide showed significant potential in attenuating the damage induced by opiates, thus repairing and restoring memory formation and retention functions. Conclusion: FMRFamide may attenuate the Tramadol- and MDMA-mediated memory dysfunction by enhancing cholinergic and glutaminergic synthesis and transporting and restoring exploratory and navigational abilities in the hippocampus of male Wistar rats.

Neural mechanisms of sentence production: a volumetric study of primary progressive aphasia.

Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task. Verb retrieval deficits partly mediated the relationship between L IFG/MFG and performance on the NAVS-SPPT. These findings underscore the importance of L IFG/MFG for sentence production and suggest that this relationship is partly accounted for by verb retrieval deficits, but not phonological loop integrity. In contrast, it is possible that the posterior temporal cortex is associated with auditory short-term memory ability, to the extent that DSF performance is a valid measure of this in aphasia.

Plasma biomarkers, memory impairment, and imaging measures of Alzheimer’s disease in American Indians

AbstractBackgroundAlzheimer’s disease (AD) is best defined in vivo using quantifiable, objective markers reflecting amyloid deposition (A), pathologic tau (T), and neurodegeneration (N). However, gold standards for ATN (imaging or cerebrospinal proteins) are expensive, invasive, and/or impractical in low resource settings. Circulating proteins offer a practical alternative. Candidate plasma markers include amyloid‐β (Aβ40&amp;42), phosphorylated tau‐181 (ptau), glial fibrillary protein (GFAP), and neurofilament light chain (NfL). However, no such markers have been evaluated in American Indians.MethodThe Strong Heart Study recruited 401 American Indians over 3 states in 2017‐2019 for MRI, cognitive testing, and clinical examination. MRI included T1 sequences, which were processed using FreeSurfer to quantify structural volumes. Neuropsychological testing incuded California Verbal Learning Test, which was operationalized into categories of memory impairment using indices of learning and recall. Plasma samples were sent to University of Gothenburg for Simoa Quanterix assay. Statistics included descriptive summary; multivariate regression; and receiver operating characteristic analysis.ResultThe study population was mean age 78 (SD 4.7, range 70‐95); majority female (71%); and 21% APOE ε4 allele carriers. An estimated 31% had any memory impairment (13.8% retrieval, 6.5% storage, 10.7% encoding). Median plasma marker values were: ptau 5.0pg/mL (range: 1.5‐442), Aβ40 128pg/mL (116‐175), Aβ42 8.2pg/mL (6.7‐9.7), GFAP 150pg/mL (0‐651), and NfL 31.6pg/mL (9.7‐343); median Aβ42:40 ratio 0.06. Comparing APOEε4 carriers to non‐carriers (Table1), ptau was +12%, Aβ40 ‐0.8%, Aβ42 ‐8.4%, Aβ4240 ‐16.7% (P = 0.006), GFAP +16.1%, NfL +3.2%, but only Aβ4240 was significant. Linear regressions with brain volumes identified significant associations for Aβ42, Aβ40, GFAP, and NfL (but not ptau) with ventricle, cortical, and overall volume; NfL was also associated with entorhinal and hippocampal volume. GFAP and ptau were significantly higher in those with memory encoding deficit; NfL higher with encoding or retrieval deficit (Table2). Although not significant, Aβ40 was lower with storage deficit, and Aβ42 with encoding or storage deficit. AUC range for plasma markers to discriminate memory impaired from intact: 0.4‐0.6.ConclusionThese data are a first look at ATN plasma markers in a population‐based cohort of American Indians, an underrepresented group in AD research. Future research should address generalizability and measurement validity.

Amygdala tau deposition best discriminates between stages of memory impairment

AbstractBackgroundThe recent development of positron emission tomography (PET) radiotracers for tau aggregates allows quantifying the regional tau burden in‐vivo. We aimed to investigate the associations between regional tauopathy and episodic memory outcomes in the AD spectrum from clinically normal to the dementia stage.MethodWe recruited 111 participants between 2019 and 2023 at the Memory Clinic of Saint‐Luc University Hospital. Each participant underwent [F18]‐MK6240 tau‐PET, 3DT1 MRI, cognitive assessment, and either lumbar puncture or [F18]‐Flutemetamol PET for amyloid status. Tau burden was quantified using Freesurfer by referring to the Desikan‐Kiliany lobe cortical parcellation, as well as in several medio‐temporal regions (MTL; i.e., entorhinal cortex, amygdala, hippocampus). Memory was assessed using three Z‐scores from the FCSRT: Sum of Free Recall (SFR), Sum of Total Recall (STR), and Sum of Delayed Free Recall (DFR). The average of these scores forms the Memory Composite Score (MCS). Participants were classified in three groups (Table 1): amyloid‐negative clinically normal participants (n = 44); non‐demented participants with AD pathology (early AD, n = 45); and AD dementia participants (n = 22). Based on their SFR and STR scores, subjects were also classified as having retrieval and/or encoding memory deficits according to a Stage of Objective Memory Impairment (SOMI) classification, inspired from Grober and colleagues (2018). Analyses were corrected for multiple comparisons.ResultIn early AD, SFR and DFR correlated with tauopathy in the bilateral entorhinal cortex (EC) and amygdala (Fig.1). MCS correlated with tauopathy in the bilateral amygdala, and the right frontal lobe. Tau levels did not correlate with STR in any regions. Moreover, MTL tauopathy differed between SOMI stages: Specifically, amygdala tauopathy gradually increased with retrieval deficits (SOMI1‐2) and encoding deficits (SOMI3‐4). In contrast, tauopathy in the EC, the temporal lobe, and the parietal lobe was elevated in all participants with memory deficits, but did not distinguish between retrieval and encoding deficits (Table 2).ConclusionTauopathy in the MTL ROIs is predictive of retrieval deficits in early stage of AD. SFR is a more sensitive measure of this early decline compared to STR. Amygdala tauopathy differs between patients with retrieval and encoding deficits.

Conceptual saliency: Core and peripheral semantic knowledge in Alzheimer’s disease

AbstractBackgroundSemantic memory impairment in Alzheimer’s disease (AD) is indicative of an actual degradation of semantic knowledge – the conceptual and factual knowledge necessary to engage with others and the physical world – rather than merely to a retrieval deficit. Historically, studies in semantic knowledge in AD have relied on predetermined sets of stimuli to probe knowledge. The analysis presented here compares the contents, sequences and organization of lists of salient concepts generated by 19 patients at the mild to moderates stages AD and by 15 age‐matched cognitively normal control individuals by means of a free‐listing task, for two semantic categories, living kinds and man‐made objects. The free elicitation by participants prevents the imposition of a priori ideas by the experimenter, which might not correspond to the native knowledge of the specific cultural group studied.MethodData collection starts with the ‘demarcation’ of a domain of knowledge X by a sample of participants who are being asked to write the names of as many items as they can conjure up, which they think belong to that domain X. Terms that appear earlier, or with higher frequency, on free‐lists indicate high consensus among respondents (i.e., the concept is an important component of the category); those items are considered as more salient in the domain under investigation.ResultEvidence of knowledge devolution is detected in the lists of participants with AD for both semantic categories. However, the core conceptual information and central aspects of the structuration of those knowledge domains are preserved to an extent. The peripheral conceptual knowledge is showing the greatest disease impact.ConclusionThe study starts the investigation of the aspects of living kinds and artefactual categorial knowledge especially resilient as neurodegeneration sets. Semantic knowledge holds the information about what one knows. Its integrity is critical in daily functioning, and interactions with others and the world at large. Because semantic memory supports various aspects of daily life, it is a prime candidate for therapeutic targets that can lead to meaningful outcomes for both patients and their care partners.

Immune activation state modulates infant engram expression across development.

Infantile amnesia is possibly the most ubiquitous form of memory loss in mammals. We investigated how memories are stored in the brain throughout development by integrating engram labeling technology with mouse models of infantile amnesia. Here, we found a phenomenon in which male offspring in maternal immune activation models of autism spectrum disorder do not experience infantile amnesia. Maternal immune activation altered engram ensemble size and dendritic spine plasticity. We rescued the same apparently forgotten infantile memories in neurotypical mice by optogenetically reactivating dentate gyrus engram cells labeled during complex experiences in infancy. Furthermore, we permanently reinstated lost infantile memories by artificially updating the memory engram, demonstrating that infantile amnesia is a reversible process. Our findings suggest not only that infantile amnesia is due to a reversible retrieval deficit in engram expression but also that immune activation during development modulates innate, and reversible, forgetting switches that determine whether infantile amnesia will occur.

Delayed recovery from ataxic dementia following liposuction

ABSTRACT A 19-year-old student developed hypoventilation and cyanosis at the end of a cosmetic liposuction procedure. She was awake, but severely abulic, disoriented, and unable to stand and walk due to severe locomotor ataxia. Neuropsychological evaluation showed psychomotor slowness, and deficits in memory encoding and retrieval, and on executive, and visuospatial and visuoperceptual tests; oral comprehension and constructional praxis were spared. ¹H-MRS showed a reduction of NAA. A year later, her cognitive and neurological exam, and NAA returned to normal, and she resumed her normal life. The severity of the acute manifestations of hypoxic encephalopathy not always entail a poor prognosis.

Case report: Neuropsychological assessment in a patient with 4H leukodystrophy

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.