Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.

Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD = 69, non-AD = 54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC = 89.8), p-tau231 (AUC = 83.4), and p-tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR < 1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217 = 15.29, ORp-tau205 = 5.05 and ORp-tau231 = 3.86) and Braak staging (ORp-tau217 = 14.29, ORp-tau205 = 5.27 and ORp-tau231 = 4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.

The Current of Consciousness: Neural Correlates and Clinical Aspects.

PURPOSE OF REVIEW: In this review, we summarize the current understanding of consciousness including its neuroanatomic basis. We discuss major theories of consciousness, physical exam-based and electroencephalographic metrics used to stratify levels of consciousness, and tools used to shed light on the neural correlates of the conscious experience. Lastly, we review an expanded category of 'disorders of consciousness,' which includes disorders that impact either the level or experience of consciousness. RECENT FINDINGS: Recent studies have revealed many of the requisite EEG, ERP, and fMRI signals to predict aspects of the conscious experience. Neurological disorders that disrupt the reticular activating system can affect the level of consciousness, whereas cortical disorders from seizures and migraines to strokes and dementia may disrupt phenomenal consciousness. The recently introduced memory theory of consciousness provides a new explanation of phenomenal consciousness that may explain better than prior theories both experimental studies and the neurologist's clinical experience. Although the complete neurobiological basis of consciousness remains a mystery, recent advances have improved our understanding of the physiology underlying level of consciousness and phenomenal consciousness.

Ante-mortem plasma phosphorylated tau (181) predicts Alzheimer's disease neuropathology and regional tau at autopsy.

Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau181) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer's disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau181 as an accurate and reliable biomarker of Alzheimer's disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer's Disease Research Center who had a plasma sample analysed for phosphorylated-tau181 between 2008 and 2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau181 was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer's disease. Average time between blood draw and death was 5.6 years (standard deviation = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau181 concentrations were associated with increased odds for having autopsy-confirmed Alzheimer's disease [AUC = 0.82, OR = 1.07, 95% CI = 1.03-1.11, P < 0.01; phosphorylated-tau standardized (z-transformed): OR = 2.98, 95% CI = 1.50-5.93, P < 0.01]. Higher plasma phosphorylated-tau181 levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02-1.09, P < 0.01) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03-1.06, P < 0.05). The association between plasma phosphorylated-tau181 and Alzheimer's disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02-1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01-1.10). There was higher discrimination accuracy for Alzheimer's disease when blood draw occurred in years closer to death; however, higher plasma phosphorylated-tau181 levels were associated with Alzheimer's disease even when blood draw occurred >5 years from death. Ante-mortem plasma phosphorylated-tau181 concentrations were associated with Alzheimer's disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer's disease. These findings support plasma phosphorylated-tau181 as a scalable biomarker for the detection of Alzheimer's disease.

Event-related Potentials Corresponding to Decision-making Under Uncertain Conditions.

BACKGROUND: Decision-making is essential to human functioning, and resolving uncertainty is an essential part of decision-making. Impaired decision-making is present in many pathological conditions, and identifying markers of decision-making under uncertainty will provide a measure of clinical impact in future studies of therapeutic intervention for impaired decision-making. OBJECTIVE: To describe EEG event-related potentials (ERPs) correlating with decision-making under uncertain conditions when compared with certain conditions. METHOD: We used a novel card-matching task based on the Wisconsin Card Sorting Test to describe the neural correlates of uncertainty, as measured by EEG, in a group of 27 neurotypical individuals. We evaluated 500-ms intervals in the 2 seconds after card presentation to identify ERPs that are associated with maximal uncertainty compared with maximal certainty. RESULTS: After correcting for multiple comparisons, we identified an ERP in the 500-1000-ms time frame (certain > uncertain, max amplitude 12.73 µV, latency 914 ms) in the left posterior inferior region of the scalp. We also found a P300-like ERP in the left frontal and parietal regions in the 0-500-ms time frame when the individuals received correct versus incorrect feedback (incorrect feedback > correct feedback, max amplitude 1.625 µV, latency 339 ms). CONCLUSION: We identified an ERP in the 500-1000-ms time frame (certain > uncertain) that may reflect the resolution of uncertainty, as well as a P300-like ERP when feedback is presented (incorrect feedback > correct feedback). These findings can be used in future studies to improve decision-making and resolve uncertainty on the described markers.

Development and Pilot of a Process for Regularly Sharing Summary Patient Safety Data.

OBJECTIVE: Dissemination of patient safety data is key to understanding safety events and improving the quality of patient care. However, there is limited guidance on how psychiatry residency programs can create a supportive environment in which to disclose and discuss such information. The authors developed and piloted a resident-led Patient Safety Presentation process at an Accreditation Council for Graduate Medical Education-accredited psychiatry residency program, sharing patient safety data while enhancing residents' education and engagement in patient safety. METHODS: From September 2020 through February 2021, the authors convened a workgroup of psychiatry residents and faculty members to devise and conduct the presentation process. The process consisted of an introductory hour-long training of residents in patient safety concepts, followed a week later by the presentation by two psychiatry residents. The authors evaluated the pilot presentation process using pre- and post-presentation resident surveys. RESULTS: The introductory training and the Patient Safety Presentation were included into the didactic schedules of all 32 program residents. Twenty (62.5%) and 17 (53.1%) residents completed the pre- and post-presentation surveys, respectively. Improvements were seen in residents' knowledge regarding the medical center's patient safety practices and perspectives on patient safety practices. On the post-presentation survey, all 17 residents reported overall satisfaction with the presentation. CONCLUSIONS: The piloted Patient Safety Presentation process increased psychiatry residents' knowledge of and engagement in patient safety. The development and pilot of the presentation process serve as an illustrative case study for other residency programs that are aspiring to grow this aspect of their curriculum.

Consciousness as a Memory System.

We suggest that there is confusion between why consciousness developed and what additional functions, through continued evolution, it has co-opted. Consider episodic memory. If we believe that episodic memory evolved solely to accurately represent past events, it seems like a terrible system-prone to forgetting and false memories. However, if we believe that episodic memory developed to flexibly and creatively combine and rearrange memories of prior events in order to plan for the future, then it is quite a good system. We argue that consciousness originally developed as part of the episodic memory system-quite likely the part needed to accomplish that flexible recombining of information. We posit further that consciousness was subsequently co-opted to produce other functions that are not directly relevant to memory per se, such as problem-solving, abstract thinking, and language. We suggest that this theory is compatible with many phenomena, such as the slow speed and the after-the-fact order of consciousness, that cannot be explained well by other theories. We believe that our theory may have profound implications for understanding intentional action and consciousness in general. Moreover, we suggest that episodic memory and its associated memory systems of sensory, working, and semantic memory as a whole ought to be considered together as the conscious memory system in that they, together, give rise to the phenomenon of consciousness. Lastly, we suggest that the cerebral cortex is the part of the brain that makes consciousness possible, and that every cortical region contributes to this conscious memory system.

Distinguishing Between Genuine and Feigned Dementia Using Event-related Potentials.

BACKGROUND: Individuals with probable Alzheimer disease (AD) may perform below cutoffs on traditional, memory-based performance validity tests. Previous studies have found success using event-related potentials (ERPs) to detect feigned neurocognitive impairment in younger populations. OBJECTIVE: To evaluate the utility of an auditory oddball task in conjunction with the P3b peak amplitude to distinguish probable AD from simulated dementia. METHOD: Twenty individuals with probable AD and 20 older healthy controls (HC) underwent an ERP auditory oddball protocol and the Test of Memory Malingering (TOMM). The HC were asked to perform honestly for one condition and to simulate dementia for the other. The individuals with probable AD were asked to perform honestly. The P3b peak amplitude and button press accuracy were collected from each participant and were analyzed to determine their effectiveness in detecting performance validity. RESULTS: The P3b peak amplitude remained stable regardless of behavioral condition in the HC group. When combined with the TOMM Trial 2 score, the P3b peak amplitude further improved the ability to correctly differentiate individuals with probable AD from HC simulating dementia with 100% sensitivity and 90% specificity. CONCLUSION: The P3b peak amplitude was found to be an effective physiologic measure of cognitive impairment in individuals with probable AD compared with HC simulating dementia. When combined with the TOMM Trial 2 score, the P3b peak amplitude served as a promising performance validity measure for differentiating individuals with probable AD from HC simulating dementia.

Educating students while recruiting underrepresented populations for Alzheimer's disease research: the Student Ambassador Program.

BACKGROUND: Increasing numbers of patients with Alzheimer's Disease and related disorders (ADRD) necessitates increasing numbers of clinicians to care for them. Educational programming related to community outreach with older adults may help inspire interest in future ADRD clinical careers, while increasing awareness of ADRD in the community and aiding recruitment of underrepresented participants into research studies. METHOD: The Boston University Alzheimer's Disease Research Center (BU ADRC) created the BU ADRC Student Ambassador Program, where medical students, graduate students, and undergraduates interested in medicine completed a curriculum during the academic year that included six educational and three outreach events, including monthly dementia-focused didactic meetings and outreach focusing on Black participant recruitment. A pre-post program survey design was implemented to assess changes in students' knowledge of and attitudes toward dementia and related disorders. RESULTS: Between September 2015 and May 2020, thirty-seven students completed the program. Following program completion, students demonstrated increased knowledge of dementia and willingness to work with patients with dementia, as well as more positive attitudes toward patients and the role of empathy in physician practice. In terms of recruitment benefits, the students helped the BU ADRC reach older adults from underrepresented groups who could serve as participants in future research studies. CONCLUSIONS: The BU ADRC Student Ambassador Program can serve as a model for other clinical research programs who wish to encourage students to consider a career in a specific field. In addition, this model has the potential to increase enrollment of participants to research studies. We discuss limitations of our initial efforts and directions for future work to quantify the anticipated benefits for student education and participant recruitment.

Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau.

INTRODUCTION: We examined the ability of plasma hyperphosphorylated tau (p-tau)181 to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL). METHODS: Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables. RESULTS: Plasma p-tau181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM. DISCUSSION: These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.

The Effectiveness of Item-Specific Encoding and Conservative Responding to Reduce False Memories in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease Dementia.

OBJECTIVE: Patients with mild Alzheimer's disease dementia are more susceptible to false memories than healthy older adults. Evidence that these patients can use cognitive strategies to reduce false memory is inconsistent. METHOD: In the present study, we examined the effectiveness of conservative responding and item-specific deep encoding strategies, alone and in combination, to reduce false memory in a categorized word list paradigm among participants with mild Alzheimer's disease dementia (AD), amnestic single-domain mild cognitive impairment (MCI), and healthy age-matched older controls (OCs). A battery of clinical neuropsychological measures was also administered. RESULTS: Although use of conservative responding alone tended to reduce performance in the MCI and OC groups, both deep encoding alone and deep encoding combined with conservative strategies led to improved discrimination for both gist memory and item-specific recollection for these two groups. In the AD group, only gist memory benefited from the use of strategies, boosted equally by deep encoding alone and deep encoding combined with conservative strategies; item-specific recollection was not improved. No correlation between the use of these strategies and performance on neuropsychological measures was found. CONCLUSIONS: These results suggest that further evaluation of these strategies is warranted as they have the potential to reduce related and unrelated memory errors and increase both gist memory and item-specific recollection in healthy older adults and individuals with amnestic MCI. Patients with AD were less able to benefit from such strategies, yet were still able to use them to reduce unrelated memory errors and increase gist memory.

Influence of self-referential mode on memory for aMCI patients.

One's concept of the self can act as a schema, in some cases facilitating memory performance but in other cases making memory more prone to errors. In this study, we attempted to induce long-lasting self-reference effects through an autobiographical mode in younger and older adults, as well as patients with amnestic mild cognitive impairment (aMCI), predicting that a self-referential mode of thought would benefit memory. Participants first either recalled autobiographical memories or described three neutral photographs in a narrative condition. This was followed by a conventional self-referencing task. At retrieval, participants completed a recognition task. Contrary to our prediction, the self-referencing benefit emerged consistently under autobiographical and narrative modes across all groups. Although our findings indicate that self-referencing can benefit memory, it carries the risk of increasing false alarm rates when induced through an autobiographical mode and consequently the strategy should be utilized with caution.

False Memories: The Other Side of Forgetting.

OBJECTIVE: To measure caregivers' and clinicians' perception of false memories in the lives of patients with memory loss due to Alzheimer's disease (AD) and mild cognitive impairment (MCI) using a novel false memories questionnaire. Our hypotheses were that false memories are occurring as often as forgetting according to clinicians and family members. METHOD: This prospective, questionnaire-based study consisting of 20 false memory questions paired with 20 forgetting questions had two forms: one for clinicians and the other for family members of older subjects. In total, 226 clinicians and 150 family members of 49 patients with AD, 44 patients with MCI, and 57 healthy older controls (OCs) completed the questionnaire. RESULTS: False memories occurred nearly as often as forgetting according to clinicians and family members of patients with MCI and AD. Family members of OCs and patients with MCI reported fewer false memories compared to those of the AD group. As Mini-Mental State Examination scores decreased, the mean score increased for both forgetting and false memories. Among clinicians, correlations were observed between the dementia severity of patients seen with both forgetting and false memories questionnaire scores as well as with the impact of forgetting and false memories on daily life. CONCLUSION: Patients with AD experience false memories almost as frequently as they do forgetting. Given how common false memories are in AD patients, additional work is needed to understand the clinical implications of these false memories on patients' daily lives. The novel false memories questionnaire developed may be a valuable tool.

Twelve tips to present an effective webinar.

Educators are increasingly invited to present via webinars rather than in-person. Webinars offer multiple advantages over in-person presentations, including the ability to speak to participants across a wide geographic area and the possibility of reduced financial and time costs for the webinar organizer, speakers, and participants. To capitalize on these advantages, educators need strategies to present effectively using this medium. Here we provide 12 tips for effective webinar presentations based upon best practices identified in the literature and the authors' experience organizing educational webinars. The 12 tips are: (1) Learn webinar logistics, (2) Conduct a needs assessment, (3) Write specific learning objectives, (4) Attend a webinar, (5) Create clear, engaging slides, (6) Develop interactive learning activities, (7) Familiarize yourself with the technology, (8) Practice your presentation, (9) Be organized, prepared, and energetic, (10) Evaluate participant learning, (11) Learn from feedback, and (12) Share your experience with the organizer. We hope these tips help presenters improve the quality and effectiveness of their webinars.

Late Positive Component Event-related Potential Amplitude Predicts Long-term Classroom-based Learning.

It is difficult to predict whether newly learned information will be retrievable in the future. A biomarker of long-lasting learning, capable of predicting an individual's future ability to retrieve a particular memory, could positively influence teaching and educational methods. ERPs were investigated as a potential biomarker of long-lasting learning. Prior ERP studies have supported a dual-process model of recognition memory that categorizes recollection and familiarity as distinct memorial processes with distinct ERP correlates. The late positive component is thought to underlie conscious recollection and the frontal N400 signal is thought to reflect familiarity [Yonelinas, A. P. Components of episodic memory: The contribution of recollection and familiarity. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 356, 1363-1374, 2001]. Here we show that the magnitude of the late positive component, soon after initial learning, is predictive of subsequent recollection of anatomical terms among medical students 6 months later.

Retained executive abilities in mild cognitive impairment are associated with increased white matter network connectivity.

PURPOSE: To describe structural network differences in individuals with mild cognitive impairment (MCI) with high versus low executive abilities, as reflected by measures of white matter connectivity using diffusion tensor imaging (DTI). MATERIALS AND METHODS: This was a retrospective, cross-sectional study. Of the 128 participants from the Alzheimer's Disease Neuroimaging Initiative database who had both a DTI scan as well as a diagnosis of MCI, we used an executive function score to classify the top 15 scoring patients as high executive ability, and the bottom-scoring 16 patients as low executive ability. Using a regions-of-interest-based analysis, we constructed networks and calculated graph theory measures on the constructed networks. We used automated tractography in order to compare differences in major white matter tracts. RESULTS: The high executive ability group yielded greater network size, density and clustering coefficient. The high executive ability group reflected greater fractional anisotropy bilaterally in the inferior and superior longitudinal fasciculi. CONCLUSIONS: The network measures of the high executive ability group demonstrated greater white matter integrity. This suggests that white matter reserve may confer greater protection of executive abilities. Loss of this reserve may lead to greater impairment in the progression to Alzheimer's disease dementia. KEY POINTS: • The MCI high executive ability group yielded a larger network. • The MCI high executive ability group had greater FA in numerous tracts. • White matter reserve may confer greater protection of executive abilities. • Loss of executive reserve may lead to greater impairment in AD dementia.

Functional brain networks involved in decision-making under certain and uncertain conditions.

PURPOSE: The aim of this study was to describe imaging markers of decision-making under uncertain conditions in normal individuals, in order to provide baseline activity to compare to impaired decision-making in pathological states. METHODS: In this cross-sectional study, 19 healthy subjects ages 18-35 completed a novel decision-making card-matching task using a Phillips T3 Scanner and a 32-channel head coil. Functional data were collected in six functional runs. In one condition of the task, the participant was certain of the rule to apply to match the cards; in the other condition, the participant was uncertain. We performed cluster-based comparison of the two conditions using FSL fMRI Expert Analysis Tool and network-based analysis using MATLAB. RESULTS: The uncertain > certain comparison yielded three clusters-a midline cluster that extended through the midbrain, the thalamus, bilateral prefrontal cortex, the striatum, and bilateral parietal/occipital clusters. The certain > uncertain comparison yielded bilateral clusters in the insula, parietal and temporal lobe, as well as a medial frontal cluster. A larger, more connected functional network was found in the uncertain condition. CONCLUSION: The involvement of the insula, parietal cortex, temporal cortex, ventromedial prefrontal cortex, and orbitofrontal cortex of the certain condition reinforces the notion that certainty is inherently rewarding. For the uncertain condition, the involvement of the prefrontal cortex, parietal cortex, striatum, thalamus, amygdala, and hippocampal involvement was expected, as these are areas involved in resolving uncertainty and rule updating. The involvement of occipital cortical involvement and midbrain involvement may be attributed to increased visual attention and increased motor control.

Response bias and response monitoring: Evidence from healthy older adults and patients with mild Alzheimer's disease.

Patients with Alzheimer's disease (AD) often exhibit an abnormally liberal response bias in recognition memory tests, responding "old" more frequently than "new." Investigations have shown patients can to shift to a more conservative response bias when given instructions. We examined if patients with mild AD could alter their response patterns when the ratio of old items is manipulated without explicit instruction. Healthy older adults and AD patients studied lists of words and then were tested in three old/new ratio conditions (30%, 50%, or 70% old items). A subset of participants provided estimates of how many old and new items they saw in the memory test. We demonstrated that both groups were able to change their response patterns without the aid of explicit instructions. Importantly, AD patients were more likely to estimate seeing greater numbers of old than new items, whereas the reverse was observed for older adults. Elevated estimates of old items in AD patients suggest their liberal response bias may be attributed to their reliance on familiarity. We conclude that the liberal response bias observed in AD patients is attributable to their believing that more of the test items are old and not due to impaired meta-memorial monitoring abilities.

Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: A voxel-based morphometry study.

Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests that exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF). This exercise-enhanced expression of growth hormones may boost synaptic plasticity, and neuronal survival and differentiation, potentially supporting function and structure in brain areas including but not limited to the hippocampus. Here, using voxel based morphometry and a standard graded treadmill test to determine cardio-respiratory fitness (Bruce protocol; ·VO2 max), we examined if entorhinal and hippocampal volumes were associated with cardio-respiratory fitness in healthy young adults (N=33). In addition, we examined if volumes were modulated by recognition memory performance and by serum BDNF, a putative marker of synaptic plasticity. Our results show a positive association between volume in right entorhinal cortex and cardio-respiratory fitness. In addition, average gray matter volume in the entorhinal cortex, bilaterally, was positively associated with memory performance. These data extend prior work on the cerebral effects of aerobic exercise and fitness to the entorhinal cortex in healthy young adults thus providing compelling evidence for a relationship between aerobic fitness and structure of the medial temporal lobe memory system.

The influence of strategic encoding on false memory in patients with mild cognitive impairment and Alzheimer's disease dementia.

Patients with Alzheimer's disease (AD) dementia exhibit high rates of memory distortions in addition to their impairments in episodic memory. Several investigations have demonstrated that when healthy individuals (young and old) engaged in an encoding strategy that emphasized the uniqueness of study items (an item-specific encoding strategy), they were able to improve their discrimination between old items and unstudied critical lure items in a false memory task. In the present study we examined if patients with AD could also improve their memory discrimination when engaging in an item-specific encoding strategy. Healthy older adult controls, patients with mild cognitive impairment (MCI) due to AD, and patients with mild AD dementia were asked to study lists of categorized words. In the Item-Specific condition, participants were asked to provide a unique detail or personal experience with each study item. In the Relational condition, they were asked to determine how each item in the list was related to the others. To assess the influence of both strategies, recall and recognition memory tests were administered. Overall, both patient groups exhibited poorer memory in both recall and recognition tests compared to controls. In terms of recognition, healthy older controls and patients with MCI due to AD exhibited improved memory discrimination in the Item-Specific condition compared to the Relational condition, whereas patients with AD dementia did not. We speculate that patients with MCI due to AD use intact frontal networks to effectively engage in this strategy.