The fading memories of youth.

The mystery of "infantile amnesia" suggests memory works differently in the developing brain.

Reaction Time Intraindividual Variability Reveals Inhibitory Deficits in Single- and Multiple-Domain Amnestic Mild Cognitive Impairment.

OBJECTIVES: Amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease and other dementias, is characterized by episodic memory impairment. Recent evidence has shown inhibitory control deficits in aMCI, but the extent of these deficits across inhibitory domains (i.e., response inhibition and interference control) and aMCI subtypes (i.e., single vs multiple domain) remains unclear. Few studies have included reaction time intraindividual variability (RT IIV) in these efforts. The aim of this study was to compare response inhibition and interference control between aMCI subtypes using measures of accuracy, mean RT, and RT IIV. METHODS: We report data from 34 individuals with single-domain aMCI (sdaMCI, 66-86 years), 20 individuals with multiple-domain aMCI (mdaMCI, 68-88 years), and 52 healthy controls (HC, 64-88 years) who completed tasks of response inhibition (Go-NoGo) and interference control (Flanker). Group differences in accuracy, mean RT, and RT IIV were examined for both tasks. RESULTS: Individuals with mdaMCI had higher RT IIV than the other groups on both tasks. In RT IIV, we observed an interference control deficit in mdaMCI and sdaMCI relative to healthy controls, a finding not observed through accuracy or mean RT. DISCUSSION: RT IIV may detect subtle differences in inhibition deficits between aMCI subtypes that may not be evident with conventional behavioral measures. Findings support the supplementary use of RT IIV when assessing early executive function deficits.

Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients.

BACKGROUND: Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer's disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). OBJECTIVE: To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. METHODS: We collected core AD markers (amyloid-ß 42 [Aß42], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks' perfusion, cerebellar volume, and processing speed. RESULTS: Perfusion was reduced in the DMN (F = 5.486, p = 0.039) and LIN (F = 12.678, p = 0.004) in APOE ɛ4 carriers compared to non-carriers. LIN perfusion correlated with CSF Aß42 levels (r = 0.678, p = 0.022) and memory impairment (PAL, number of errors, r = -0.779, p = 0.002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. CONCLUSION: Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE ɛ4, and memory impairment.

Anterior Thalamic Inputs Are Required for Subiculum Spatial Coding, with Associated Consequences for Hippocampal Spatial Memory.

Just as hippocampal lesions are principally responsible for "temporal lobe" amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, "diencephalic" amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology.SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.

Resting State Alpha Electroencephalographic Rhythms Are Differently Related to Aging in Cognitively Unimpaired Seniors and Patients with Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

BACKGROUND: In relaxed adults, staying in quiet wakefulness at eyes closed is related to the so-called resting state electroencephalographic (rsEEG) rhythms, showing the highest amplitude in posterior areas at alpha frequencies (8-13 Hz). OBJECTIVE: Here we tested the hypothesis that age may affect rsEEG alpha (8-12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with mild cognitive impairment due to Alzheimer's disease (ADMCI). METHODS: Clinical and rsEEG datasets in 63 ADMCI and 60 Nold individuals (matched for demography, education, and gender) were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14-30 Hz) and gamma (30-40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles). RESULTS: As compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. On the contrary, in relation to the younger ADMCI subgroups, the older one displayed a lesser reduction in those rhythms. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions revealed by neuroimaging, and clinical and neuropsychological scores. CONCLUSION: The present results suggest that age may represent a deranging factor for dominant rsEEG alpha rhythms in Nold seniors, while rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants related to earlier versus later onset of the AD.

Distinctive Alterations of Functional Connectivity Strength between Vascular and Amnestic Mild Cognitive Impairment.

Widespread structural and functional alterations have been reported in the two highly prevalent mild cognitive impairment (MCI) subtypes, amnestic MCI (aMCI) and vascular MCI (VaMCI). However, the changing pattern in functional connectivity strength (FCS) remains largely unclear. The aim of the present study is to detect the differences of FCS and to further explore the detailed resting-state functional connectivity (FC) alterations among VaMCI subjects, aMCI subjects, and healthy controls (HC). Twenty-six aMCI subjects, 31 VaMCI participants, and 36 HC participants underwent cognitive assessments and resting-state functional MRI scans. At first, one-way ANCOVA and post hoc analysis indicated significant decreased FCS in the left middle temporal gyrus (MTG) in aMCI and VaMCI groups compared to HC, especially in the VaMCI group. Then, we selected the left MTG as a seed to further explore the detailed resting-state FC alterations among the three groups, and the results indicated that FC between the left MTG and some frontal brain regions were significantly decreased mainly in VaMCI. Finally, partial correlation analysis revealed that the FC values between the left MTG and left inferior frontal gyrus were positively correlated with the cognitive performance episodic memory and negatively related to the living status. The present study demonstrated that different FCS alterations existed in aMCI and VaMCI. These findings may provide a novel insight into the understanding of pathophysiological mechanisms underlying different MCI subtypes.

Assessing Sleep Architecture With Polysomnography During Posttraumatic Amnesia After Traumatic Brain Injury: A Pilot Study.

BACKGROUND: Early-onset sleep disturbance is common following moderate to severe traumatic brain injury (TBI) and often emerges while patients are in posttraumatic amnesia (PTA). However, sleep disruptions during this subacute recovery phase are not well-defined, and research often utilizes indirect measures (actigraphy) that quantify sleep based on activity. This study aims to examine sleep macro-architecture and sleep quality directly with ambulatory polysomnography (PSG) and measure endogenous salivary melatonin levels for patients experiencing PTA following moderate to severe TBI. METHOD: Participants were recruited from an inpatient TBI rehabilitation unit. Nighttime PSG was administered at the patient's bedside. Two saliva specimens were collected for melatonin testing on a separate evening (24:00 and 06:00 hours) using melatonin hormone profile test kits. RESULTS: Of 27 patients in whom PSG was recorded, the minimum required monitoring time occurred in n =17 (adherence: 63%) at a median of 37.0 days (quartile 1 [Q1] to quartile 3 [Q3]: 21.5-50.5) postinjury. Median non-rapid eye movement (NREM) and REM sleep proportions were similar to normal estimates. Slow-wave sleep was reduced and absent in 35.3% of patients. Sleep periods appeared fragmented, and median sleep efficiency was reduced (63.4%; Q1-Q3: 55.1-69.2). Median melatonin levels at both timepoints were outside the normal range of values specified for this test (from Australian Clinical Labs). CONCLUSION: This study reports that ambulatory PSG and salivary melatonin assessment are feasible for patients experiencing PTA and offers new insight into the extent of sleep disturbance. Further research is necessary to understand associations between PTA and sleep disturbance.

Increased segregation of structural brain networks underpins enhanced broad cognitive abilities of cognitive training.

A major challenge in the cognitive training field is inducing broad, far-transfer training effects. Thus far, little is known about the neural mechanisms underlying broad training effects. Here, we tested a set of competitive hypotheses regarding the role of brain integration versus segregation underlying the broad training effect. We retrospectively analyzed data from a randomized controlled trial comparing neurocognitive effects of vision-based speed of processing training (VSOP) and an active control consisting of mental leisure activities (MLA) in older adults with MCI. We classified a subset of participants in the VSOP as learners, who showed improvement in executive function and episodic memory. The other participants in the VSOP (i.e., VSOP non-learners) and a subset of participants in the MLA (i.e., MLA non-learners) served as controls. Structural brain networks were constructed from diffusion tensor imaging. Clustering coefficients (CCs) and characteristic path lengths were computed as measures of segregation and integration, respectively. Learners showed significantly greater global CCs after intervention than controls. Nodal CCs were selectively enhanced in cingulate cortex, parietal regions, striatum, and thalamus. Among VSOP learners, those with more severe baseline neurodegeneration had greater improvement in segregation after training. Our findings suggest broad training effects are related to enhanced segregation in selective brain networks, providing insight into cognitive training related neuroplasticity.

One-trial perceptual learning in the absence of conscious remembering and independent of the medial temporal lobe.

A degraded, black-and-white image of an object, which appears meaningless on first presentation, is easily identified after a single exposure to the original, intact image. This striking example of perceptual learning reflects a rapid (one-trial) change in performance, but the kind of learning that is involved is not known. We asked whether this learning depends on conscious (hippocampus-dependent) memory for the images that have been presented or on an unconscious (hippocampus-independent) change in the perception of images, independently of the ability to remember them. We tested five memory-impaired patients with hippocampal lesions or larger medial temporal lobe (MTL) lesions. In comparison to volunteers, the patients were fully intact at perceptual learning, and their improvement persisted without decrement from 1 d to more than 5 mo. Yet, the patients were impaired at remembering the test format and, even after 1 d, were impaired at remembering the images themselves. To compare perceptual learning and remembering directly, at 7 d after seeing degraded images and their solutions, patients and volunteers took either a naming test or a recognition memory test with these images. The patients improved as much as the volunteers at identifying the degraded images but were severely impaired at remembering them. Notably, the patient with the most severe memory impairment and the largest MTL lesions performed worse than the other patients on the memory tests but was the best at perceptual learning. The findings show that one-trial, long-lasting perceptual learning relies on hippocampus-independent (nondeclarative) memory, independent of any requirement to consciously remember.

Connectome-based model predicts episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment.

OBJECTIVE: To explore whether the whole brain resting-state functional connectivity (rs-FC) could predict episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment. METHOD: This study included 33 cognitive normal (CN), 26 subjective cognitive decline (SCD) and 27 amnestic mild cognitive impairment (aMCI) patients, and all the participants completed resting-state fMRI (rs-fMRI) scan and neuropsychological scale test data. Connectome-based predictive modeling (CPM) based on the rs-FC data was used to predict the auditory verbal learning test-delayed recall (AVLT-DR) scores, which measured episodic memory in individuals. Pearson correlation between each brain connection in the connectivity matrices and AVLT-DR scores was computed across the patients in predementia stages of Alzheimer's disease (AD). The Pearson correlation coefficient values separated into a positive network and a negative network. Predictive networks were then defined and employed by calculating positive and negative network strengths. CPM with leave-one-out cross-validation (LOOCV) was conducted to train linear models to respectively relate positive and negative network strengths to AVLT-DR scores in the training set. During the testing procedure, each left-out testing subject's strengths of positive and negative network was normalized using the parameters acquired during training procedure, and then the trained models were used to predict the testing participant's AVLT-DR score. RESULTS: The negative network predictive model tested LOOCV significantly predicted individual differences in episodic memory from rs-FC. Key nodes that brain regions contributed to the prediction model were mainly located in the prefrontal cortex, frontal cortex, parietal cortex and temporal lobe. CONCLUSION: Our findings demonstrated that rs-FC among multiple neural systems could predict episodic memory at the individual level.

Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

OBJECTIVE: To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings. METHODS: We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry. RESULTS: Three patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity. CONCLUSION: AMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.

Evaluation of Phytochemical, Antioxidant, and Memory-Enhancing Activity of Garuga pinnata Roxb. Bark and Bryophyllum pinnatum (Lam) Oken. Leaves.

Garugapinnata Roxb. (Burseraceae) is a medium-sized tree widely available all over the tropical regions of Asia. Bryophyllum pinnatum (Lam) Oken. (Crassulaceae) is an indigenous and exotic plant grown in tropical regions. Both plants have been used for their anti-inflammatory, antioxidant, anticancer, wound healing, antidiabetic activities, etc. This investigation was designed to explore the result shown by methanolic extract of Garuga pinnata bark and Bryophyllum pinnatum leaves, on cognitive power and retention of the memory in experimental mice along with quantification of phenolic compounds and DPPH radicals neutralizing capacity. The memory-enhancing activity was determined by the elevated plus-maze method in Scopolamine-induced amnesic mice, using Piracetam as allopathic and Shankhpushpi as ayurvedic standard drugs. Two doses (200 and 400 mg/kg p.o.) of both extracts were administered to mice up to 8 consecutive days; transfer latency of individual group was recorded after 45 minutes and memory of the experienced things was examined after 1 day. DPPH assay method and the Folin-Ciocalteu method were employed to determine antioxidant potency and total phenol amount, respectively. 400 mg/kg of the methanolic B. pinnatum bark extract significantly improved memory and learning of mice with transfer latency (TL) of 32.75 s, which is comparable to that of standard Piracetam (21.78 s) and Shankhpushpi (27.83 s). Greater phenolic content was quantified in B. pinnatum bark extract (156.80 ± 0.33 µg GAE/mg dry extract) as well as the antioxidant potency (69.77% of free radical inhibition at the 100 µg/mL concentration). Our study proclaimed the scientific evidence for the memory-boosting effect of both plants.

High ethanol preference and dissociated memory are co-occurring phenotypes associated with hippocampal GABAAR-δ receptor levels.

Alcohol use disorder (AUD) frequently co-occurs with dissociative disorders and disorders with dissociative symptoms, suggesting a common neurobiological basis. It has been proposed that facilitated information processing under the influence of alcohol, resulting in the formation of dissociated memories, might be an important factor controlling alcohol use. Access to such memories is facilitated under the effect of alcohol, thus further reinforcing alcohol use. To interrogate possible mechanisms associated with these phenotypes, we used a mouse model of dissociative amnesia, combined with a high-alcohol preferring (HAP) model of AUD. Dissociated memory was induced by activation of hippocampal extrasynaptic GABA type A receptor delta subunits (GABAAR-δ), which control tonic inhibition and to which ethanol binds with high affinity. Increased ethanol preference was associated with increased propensity to form dissociated memories dependent on GABAAR-δ in the dorsal hippocampus (DH). Furthermore, the DH level of GABAAR-δ protein, but not mRNA, was increased in HAP mice, and was inversely correlated to the level of miR-365-3p, suggesting an miRNA-mediated post-transcriptional mechanism contributing to elevated GABAAR-δ. The observed changes of DH GABAAR-δ were associated with a severe reduction of excitatory projections stemming from GABAAR-δ-containing pyramidal neurons in the subiculum and terminating in the mammillary body. These results suggest that both molecular and circuit dysfunction involving hippocampal GABAAR-δ receptors might contribute to the co-occurrence of ethanol preference and dissociated information processing.

Phasic alerting increases visual processing speed in amnestic mild cognitive impairment.

External warning cues temporarily increase the brain's sensitivity for upcoming events, helping individuals to flexibly adapt their reactions to the requirements of complex visual environments. Previous studies reported that younger and cognitively normal older adults profit from phasic alerting cues. Such an intact phasic alerting mechanism could be even more relevant in individuals with Alzheimer's disease who are characterized by reduced processing capacities. The present study employed a theory of visual attention based verbal whole report paradigm with auditory cues in order to investigate phasic alerting effects in amnestic mild cognitive impairment (aMCI). Patients with aMCI were also compared to a previously reported sample of cognitively normal older adults. In patients with aMCI, visual processing speed was higher in the cue compared to the no-cue condition. Further, visual processing speed was reduced in patients with aMCI compared to cognitively normal older adults. Taken together, the results suggest that the processing system of patients with aMCI exhibits general declines but can still integrate auditory warning signals on a perceptual level.

Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes.

How acute hyperglycaemia affects memory functions and functional brain responses in individuals with and without type 2 diabetes is unclear. Our aim was to study the association between acute hyperglycaemia and working, semantic, and episodic memory in participants with type 2 diabetes compared to a sex- and age-matched control group. We also assessed the effect of hyperglycaemia on working memory-related brain activity. A total of 36 participants with type 2 diabetes and 34 controls (mean age, 66 years) underwent hyperglycaemic clamp or placebo clamp in a blinded and randomised order. Working, episodic, and semantic memory were tested. Overall, the control group had higher working memory (mean z-score 33.15 ± 0.45) than the group with type 2 diabetes (mean z-score 31.8 ± 0.44, p = 0.042) considering both the placebo and hyperglycaemic clamps. Acute hyperglycaemia did not influence episodic, semantic, or working memory performance in either group. Twenty-two of the participants (10 cases, 12 controls, mean age 69 years) were randomly invited to undergo the same clamp procedures to challenge working memory, using 1-, 2-, and 3-back, while monitoring brain activity by blood oxygen level-dependent functional magnetic resonance imaging (fMRI). The participants with type 2 diabetes had reduced working memory during the 1- and 2-back tests. fMRI during placebo clamp revealed increased BOLD signal in the left lateral frontal cortex and the anterior cingulate cortex as a function of working memory load in both groups (3>2>1). During hyperglycaemia, controls showed a similar load-dependent fMRI response, whereas the type 2 diabetes group showed decreased BOLD response from 2- to 3-back. These results suggest that impaired glucose metabolism in the brain affects working memory, possibly by reducing activity in important frontal brain areas in persons with type 2 diabetes.

Neurocognitive Plasticity Is Associated with Cardiorespiratory Fitness Following Physical Exercise in Older Adults with Amnestic Mild Cognitive Impairment.

BACKGROUND: Aerobic training has been shown to promote structural and functional neurocognitive plasticity in cognitively intact older adults. However, little is known about the neuroplastic potential of aerobic exercise in individuals at risk of Alzheimer's disease (AD) and dementia. OBJECTIVE: We aimed to explore the effect of aerobic exercise intervention and cardiorespiratory fitness improvement on brain and cognitive functions in older adults with amnestic mild cognitive impairment (aMCI). METHODS: 27 participants with aMCI were randomized to either aerobic training (n = 13) or balance and toning (BAT) control group (n = 14) for a 16-week intervention. Pre- and post-assessments included functional MRI experiments of brain activation during associative memory encoding and neural synchronization during complex information processing, cognitive evaluation using neuropsychological tests, and cardiorespiratory fitness assessment. RESULTS: The aerobic group demonstrated increased frontal activity during memory encoding and increased neural synchronization in higher-order cognitive regions such as the frontal cortex and temporo-parietal junction (TPJ) following the intervention. In contrast, the BAT control group demonstrated decreased brain activity during memory encoding, primarily in occipital, temporal, and parietal areas. Increases in cardiorespiratory fitness were associated with increases in brain activationin both the left inferior frontal and precentral gyri. Furthermore, changes in cardiorespiratory fitness were also correlated with changes in performance on several neuropsychological tests. CONCLUSION: Aerobic exercise training may result in functional plasticity of high-order cognitive areas, especially, frontal regions, among older adults at risk of AD and dementia. Furthermore, cardiorespiratory fitness may be an important mediating factor of the observed changes in neurocognitive functions.

Memory Resilience in Alzheimer Disease With Primary Progressive Aphasia.

OBJECTIVE: To determine whether memory is preserved longitudinally in primary progressive aphasia (PPA) associated with Alzheimer disease (AD) and to identify potential factors that maintain memory despite underlying neurofibrillary degeneration of mediotemporal memory areas. METHODS: Longitudinal memory assessment was done in 17 patients with PPA with autopsy or biomarker evidence of AD (PPA-AD) and 14 patients with amnestic dementia of the Alzheimer type with AD at autopsy (DAT-AD). RESULTS: In PPA-AD, episodic memory, tested with nonverbal items, was preserved at the initial testing and showed no decline at retesting 2.35 ± 0.78 years later, at which time symptoms had been present for 6.26 ± 2.21 years. In contrast, language functions declined significantly during the same period. In DAT-AD, both verbal memory and language declined with equal severity. Although imaging showed asymmetric left-sided mediotemporal atrophy in PPA-AD, autopsy revealed bilateral hippocampo-entorhinal neurofibrillary degeneration at Braak stages V and VI. Compared to DAT-AD, however, the PPA-AD group had lower incidence of APOE ε4 and of mediotemporal TAR DNA-binding protein 43 (TDP-43) pathology. CONCLUSIONS: Memory preservation in PPA is not just an incidental finding at onset but a core feature that persists for years despite the hippocampo-entorhinal AD neuropathology that is as severe as that of DAT-AD. Asymmetry of mediotemporal atrophy and a lesser impact of APOE ε4 and of TDP-43 on the integrity of memory circuitry may constitute some of the factors underlying this resilience. Our results also suggest that current controversies on memory in PPA-AD reflect inconsistencies in the diagnosis of logopenic PPA, the clinical variant most frequently associated with AD. CLINICALTRIALSGOV IDENTIFIER: NCT00537004 and NCT03371706.

Brain Activity of Benzoate, a D-Amino Acid Oxidase Inhibitor, in Patients With Mild Cognitive Impairment in a Randomized, Double-Blind, Placebo Controlled Clinical Trial.

BACKGROUND: Current anti-dementia drugs cannot benefit mild cognitive impairment (MCI). Sodium benzoate (a D-amino acid oxidase [DAO] inhibitor) has been found to improve the cognitive function of patients with early-phase Alzheimer's disease (mild Alzheimer's disease or MCI). However, its effect on brain function remains unknown. This study aimed to evaluate the influence of benzoate on functional magnetic resonance imaging in patients with amnestic MCI. METHODS: This was a 24-week, randomized, double-blind, placebo-controlled trial that enrolled 21 patients with amnestic MCI and allocated them randomly to either of 2 treatment groups: (1) benzoate group (250-1500 mg/d), or (2) placebo group. We assessed the patients' working memory, verbal learning and memory, and resting-state functional magnetic resonance imaging and regional homogeneity (ReHo) maps at baseline and endpoint. RESULTS: Resting-state ReHo decreased in right orbitofrontal cortex after benzoate treatment but did not change after placebo. Moreover, after benzoate treatment, the change in working memory was positively correlated with the change in ReHo in right precentral gyrus and right middle occipital gyrus; and the change in verbal learning and memory was positively correlated with the change in ReHo in left precuneus. In contrast, after placebo treatment, the change in working memory or in verbal learning and memory was not correlated with the change in ReHo in any brain region. CONCLUSION: The current study is the first to our knowledge to demonstrate that a DAO inhibitor, sodium benzoate herein, can alter brain activity as well as cognitive functions in individuals with MCI. The preliminary finding lends supports for DAO inhibition as a novel approach for early dementing processes.

Does consciousness overflow cognitive access? Novel insights from the new phenomenon of attribute amnesia.

The moment we open our eyes, we experience a rich and detailed visual world, but the amount of information available to report is rather limited. This dissociation relates to a major debate regarding the nature of visual consciousness. The overflow argument suggests that our conscious experience is quite rich and far beyond what can be reported, standing in sharp contrast to the no-overflow argument that visual consciousness is severely impoverished and limited to what can be reported. In this paper, we systematically reviewed existing evidence in favor of the overflow argument, including studies of several variations of the iconic memory paradigm and the divided attention paradigm, as well as studies of neural correlates of consciousness. Simultaneously, we expounded some critical objections and alternative interpretations to such evidence, as well as some opposing evidence. Finally, we introduced a series of our recent studies based on a striking phenomenon of attribute amnesia, which we believe could provide new insight into the overflow view of visual consciousness.

Factors Affecting Participation in Physical Therapy During Posttraumatic Amnesia.

OBJECTIVES: To examine the effect of agitation, cognitive impairment, fatigue, and pain on physical therapy participation and outcomes during posttraumatic amnesia (PTA) after traumatic brain injury (TBI). DESIGN: Prospective longitudinal study. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: Participants (N=77) with moderate-to-severe TBI who were deemed to be experiencing PTA using the Westmead Post-Traumatic Amnesia Scale. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Pittsburgh Rehabilitation Participation Scale and time in therapy (min) were recorded twice daily after routine physical therapy sessions during PTA. The FIM-motor (select items related to physical therapy) score rated on admission and after emergence from PTA was used to calculate FIM-motor change. RESULTS: Agitation was associated with lower participation in therapy. The presence of agitation and pain both predicted lower FIM-motor change at emergence from PTA. Higher levels of cognitive impairment and fatigue were also associated with lower participation and less time in therapy. CONCLUSIONS: The presence of agitation, fatigue, pain, and cognitive impairment impede rehabilitation success during PTA. This study strengthens the case for implementing environmental and behavioral recommendations, such as conducting therapy earlier in the day within a familiar space (ie, on the ward) and tailoring session duration to patient needs. This is with the aim of minimizing fatigue, agitation, and pain, while promoting cognitive recovery and arousal during PTA to maximize physical gains. Further research is warranted to examine the factors associated with rehabilitation success across other therapeutic disciplines.