Investigating underlying brain structures and influence of mild and subjective cognitive impairment on dual-task performance in people with Parkinson's disease.

Cognitive impairment can affect dual-task abilities in Parkinson's disease (PD), but it remains unclear whether this is also driven by gray matter alterations across different cognitive classifications. Therefore, we investigated associations between dual-task performance during gait and functional mobility and gray matter alterations and explored whether these associations differed according to the degree of cognitive impairment. Participants with PD were classified according to their cognitive function with 22 as mild cognitive impairment (PD-MCI), 14 as subjective cognitive impairment (PD-SCI), and 20 as normal cognition (PD-NC). Multiple regression models associated dual-task absolute and interference values of gait speed, step-time variability, and reaction time, as well as dual-task absolute and difference values for Timed Up and Go (TUG) with PD cognitive classification. We repeated these regressions including the nucleus basalis of Meynert, dorsolateral prefrontal cortex, and hippocampus. We additionally explored whole-brain regressions with dual-task measures to identify dual-task-related regions. There was a trend that cerebellar alterations were associated with worse TUG dual-task in PD-SCI, but also with higher dual-task gait speed and higher dual-task step-time variability in PD-NC. After multiple comparison corrections, no effects of interest were significant. In summary, no clear set of variables associated with dual-task performance was found that distinguished between PD cognitive classifications in our cohort. Promising but non-significant trends, in particular regarding the TUG dual-task, do however warrant further investigation in future large-scale studies.

Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Research progress on the regulatory mechanisms of Irisin on cognitive dysfunction in patients with Alzheimer's disease and the interventional role of Irisin in associated diseases.

Irisin, a peptide produced during exercise, is believed to play a role in regulating energy levels within the body. Moreover, Irisin has the ability to traverse the blood-brain barrier and engage in various pathophysiological processes within the central nervous system. An increasing body of research identifies Irisin as a significant therapeutic target for neurodegenerative diseases, indicating a strong link between Irisin and the development of cognitive impairments. In this paper, we present a concise review of effects of different types of exercise on Irisin production, and the mechanisms underlying the Irisin's intervention in various diseases including metabolic diseases, kidney injury and depression. Following this, we delve into an in-depth exploration of its role in modulating cognitive dysfunction among patients with Alzheimer's disease (AD), focusing on recent advancements in three critical areas: neuroinflammation, mitochondrial dysfunction, and protein misfolding. Finally, we put forth 3 hypotheses: (1) exercise-induced fibronectin type III domain containing protein 5 (FNDC5) stimulation and subsequent Irisin cleavage may be associated with the stress response in energy metabolism; (2) Irisin, as a myokine, likely plays a role in mitochondrial repair mechanisms to ameliorate cognitive impairment in AD patients; (3) Irisin is a homeostatic factor that maintains energy homeostasis and is closely related to the dynamic stability of the body's internal environment.

Relationship between cognitive function and functional outcomes in remitted major depression.

BACKGROUND: Few studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear. METHODS: Participants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission. RESULTS: According to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31-0.93, p = 0.030) and IED (95%CI = 1.01-1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes. CONCLUSION: Better performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory.

Prevalence and Associated Clinical Characteristics of Walking-Related Motor, Cognitive, and Fatigability in Progressive Multiple Sclerosis: Baseline Results From the CogEx Study.

BACKGROUND: People with progressive multiple sclerosis (PMS) present motor (eg, walking) and cognitive impairments, and report fatigue. Fatigue encompasses fatigability which is objectively measured by the capacity to sustain a motor or cognitive task. OBJECTIVE: To investigate the prevalence of walking and cognitive fatigability (CF) and the associated clinical characteristics in a large sample of PMS patients. METHODS: PMS patients (25-65 years old) were included from 11 sites (Europe and North America), having cognitive impairment (1.28 standard deviation below normative data for the symbol digit modality test [SDMT]). Walking fatigability (WF) was assessed using the distance walk index (DWI) and CF using the SDMT (scores from the last 30 seconds compared to the first 30 seconds). Additional measures were: cognitive assessment-Brief International Cognitive Assessment for multiple sclerosis (MS), cardiorespiratory fitness, 6-minute walk, physical activity, depressive symptoms, perceived fatigue-Modified Fatigue Impact Scale (MFIS), MS impact-MSIS-29, and walking ability. RESULTS: Of 298 participants, 153 (51%) presented WF (DWI = -28.9 ± 22.1%) and 196 (66%) presented CF (-29.7 ± 15%). Clinical characteristics (EDSS, disease duration, and use of assistive device) were worse in patients with versus without WF. They also presented worse scores on MSIS-29 physical, MFIS total and physical and reduced physical capacity. CF patients scored better in the MSIS-29 physical and MFIS psychosocial, compared to non-CF group. Magnitude of CF and WF were not related. CONCLUSIONS: Half of the cognitively-impaired PMS population presented WF which was associated with higher disability, physical functions, and fatigue. There was a high prevalence of CF but without strong associations with clinical, cognitive, and physical functions. TRIAL REGISTRATION NUMBER: The "CogEx-study," www.clinicaltrial.gov identifier number: NCT03679468.

Traumatic Brain Injury Characteristics Are Not Related to Neurocognitive Decline in Older Adults: A Nationwide Longitudinal Cohort Study.

OBJECTIVE: Evaluate whether traumatic brain injury (TBI) characteristics, age of injury, or recency of injury predicts the course of neurocognitive decline and/or increases conversion rates to mild cognitive impairment (MCI) or dementia. METHODS: Data were obtained from the National Alzheimer's Coordinating Center for participants 50-85 years old with 3-5 visits from 2015 to 2022, with or without TBI history (TBI+ = 508; TBI- = 2,382). Groups were stratified by self-reported TBI history (i.e., single TBI without loss of consciousness [LOC], single TBI with LOC, multiple TBI without LOC, and multiple TBI with LOC), age of most recent TBI, and recency of TBI. Mixed linear models compared neuropsychological composite trajectories (executive functioning/attention/speed, language, memory, and global), co-varying for age, gender, education, apolipoprotein E4 status, race/ethnicity, and baseline diagnosis (normal aging n = 1,720, MCI n = 749, or dementia n = 417). Logistic binary regression examined MCI/dementia conversion rates. RESULTS: There was a slightly higher frequency of MCI/dementia in those with multiple TBIs (50% to 60% with and without LOC, compared to 39% with no TBI) at baseline, but longitudinal trajectories were similar. TBI history, age of injury, or recency of injury did not impact neurocognitive trajectories or conversion rates to MCI/dementia (all p's > .01). CONCLUSIONS: TBI history, regardless of injury characteristics, age of injury, or recency of injury, did not worsen neurocognitive decline or MCI/dementia conversion. Additional longitudinal research in more diverse cohorts with a wider range of TBI severity is needed to evaluate the specific factors and possible mechanisms in which TBI may increase dementia risk.

Association between Subjective Cognitive Complaints and Incident Functional Impairment in Parkinson's Disease.

BACKGROUND: Early identification of subjective cognitive complaints (SCC) in Parkinson's disease (PD) may improve patient care if it predicts cognition-related functional impairment (CFI). OBJECTIVES: The aim was to determine the cross-sectional and longitudinal association between SCC and CFI in PD. METHODS: Data were obtained from Fox Insight, an online longitudinal study that collects PD patient-reported outcomes. Participants completed a PD Patient Report of Problems that asked participants for their five most bothersome disease problems. SCCs were placed into eight categories through human-in-the-loop curation and classification. CFI had a Penn Parkinson's Daily Activities Questionnaire (PDAQ-15) score ≤49. Cox proportional hazards models and Kaplan-Meier survival analyses determined if baseline SCC was associated with incident CFI. RESULTS: The PD-PROP cohort (N = 21,160) was 55.8% male, mean age was 65.9 years, and PD duration was 4.8 years. At baseline, 31.9% (N = 6750) of participants reported one or more SCCs among their five most bothersome problems, including memory (13.2%), language/word finding (12.5%), and concentration/attention (9.6%). CFI occurred in 34.7% (N = 7332) of participants. At baseline, SCC was associated with CFI (P-value <0.001). SCC at baseline was associated with incident CFI (hazard ratio [HR] = 1.58 [95% confidence interval: 1.45, 1.72], P-value <0.001), as did cognitive impairment not otherwise specified (HR = 2.31), executive abilities (HR = 1.97), memory (HR = 1.85), and cognitive slowing (HR = 1.77) (P-values <0.001). Kaplan-Meier curves showed that by year 3 an estimated 45% of participants with any SCC at baseline developed new-onset CFI. CONCLUSIONS: Self-reported bothersome cognitive complaints are associated with new-onset CFI in PD. Remote electronic assessment can facilitate widespread use of patient self-report at population scale. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

An examination of semantic performance in mild cognitive impairment progressors and nonprogressors.

OBJECTIVE: Mild cognitive impairment (MCI) is a risk factor for developing Alzheimer's disease (AD), and about half of older people with MCI will progress to AD within the next 5 years. The aim of the present study was to compare the semantic performance of MCI progressors (MCI-p) and nonprogressors (MCI-np). The hypothesis was that MCI-p would present with poorer semantic performance relative to MCI-np at baseline, indicating that semantic deficits may increase the risk of future decline toward AD. METHOD: Fifty-six MCI participants (aged 65-89) from the Consortium for Early Identification of Alzheimer's Disease-Quebec study were analyzed, with 18 progressing and 38 remaining stable over 2 years. Analysis of covariance assessed their initial semantic and nonsemantic cognitive performance, and mixed analyses of variance gauged longitudinal patterns of cognitive decline at the 2-year follow-up. RESULTS: In the semantic domain, MCI-p performed significantly worse than MCI-np at baseline on two semantic tests (category fluency and object decision). In other cognitive domains, MCI-p performed worse than MCI-np on a test of executive functions (cognitive flexibility) but showed similar performance on a test of episodic memory. There were no significant differences between groups in the rates of progression on semantic tests over the 2-year period, but a steeper decline was observed in MCI-p at follow-up on tests of global cognition, episodic memory, and processing speed. CONCLUSION: This suggest that MCI patients who present with semantic memory impairment in addition to episodic memory impairment are at greater risk of future progression to AD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impact of cataract surgery on cognitive impairment in older people.

OBJECTIVES: To examine the impact of cataract surgery on mild cognitive impairment (MCI) and dementia in older people. METHODS: This prospective observational study included patients aged 75 years and older who underwent cataract surgery between 2019 and 2021. Mini-mental state examination (MMSE) and MMSE for the visually impaired (MMSE-blind) were measured to evaluate cognitive function before and 3 months after cataract surgery. MMSE score at baseline was used to categorize patients into dementia (MMSE ≤ 23) and MCI groups (23 < MMSE ≤ 27). Logistic regression models were used to estimate associations between improvement in cognitive function and other factors. RESULTS: Of 132 patients screened for inclusion in the study, 88 met the inclusion criteria; 39 patients were assigned to the dementia group (mean age, 85.7 ± 4.2 years) and 49 to the MCI group (mean age, 84.2 ± 3.4 years). The MCI group showed significant improvement from before to after surgery in the MMSE score (25.65 ± 1.03 vs. 27.08 ± 1.99, respectively, p < 0.001) and MMSE-blind score (18.04 ± 1.14 vs. 19.41 ± 2.01, respectively, p < 0.001). Cognitive function improved significantly in the MCI group compared with the dementia group (odds ratio, 2.85; 95% confidence interval, 1.02-7.97; and p = 0.046). CONCLUSIONS: Cataract surgery significantly increases cognitive test scores in older patients with MCI. After cataract surgery, the likelihood of improvement in cognitive function may be highly dependent on a patient's preoperative cognitive state.

Disinhibition of hippocampal parvalbumin interneurons on pyramidal neurons participates in LPS-induced cognitive dysfunction.

BACKGROUND: The vulnerability of hippocampal pyramidal (PY) neurons played a key role in the onset of cognitive impairment. Multiple researches revealed that neuroinflammation together with microglia activation and parvalbumin (PV) interneurons participated in the pathogenesis of cognitive dysfunction. However, the underlying mechanism was still unclear. This study aimed to determine whether microglia activation would induce PV interneurons impairment and PY neurons disinhibition, and as a result, promote cognitive dysfunction after lipopolysaccharide (LPS) challenge. METHODS: Male C57BL/6J mice were injected with LPS to establish systemic inflammation model, and animal behavioral tests were performed. For chemogenetics, the virus was injected bilaterally into the CA1 region. Clozapine N-Oxide (CNO) was used to activate the PV interneurons. Whole-cell patch clamp recording was applied to detect spontaneous inhibitory post synaptic current (sIPSC) and spontaneous excitatory post synaptic current (sEPSC) of PY neurons in the CA1 region. RESULTS: LPS induced hippocampal dependent memory impairment, which was accompanied with microglia activation. Meanwhile, PV protein level in hippocampus were decreased, and IPSCs of PY neurons in the CA1 were also suppressed. Minocycline reversed all the above changes. In addition, rescuing PV function with CNO improved memory impairment, sIPSCs of PY neurons and perisomatic PV boutons around PY neurons without affecting microglia activation. CONCLUSION: Disinhibition of hippocampal parvalbumin interneurons on pyramidal neurons participates in LPS-induced cognitive dysfunction.

Cognitive Impairment in Patients With Cardiac Disease: Implications for Clinical Practice.

Cognitive impairment is common in patients with cardiovascular disease. One in 3 patients presenting at cardiology clinics have some degree of cognitive impairment, depending on the cardiac condition, comorbidities, and age. In up to half of these cases cognitive impairment may go unrecognized; however, it may affect self-management and treatment adherence. The high prevalence of cognitive impairment in patients with cardiac disease is likely due to shared risk factors, as well as direct consequences of cardiac dysfunction on the brain. Moreover, cardiac interventions may have beneficial as well as adverse effects on cognitive functioning. In this review, we describe prevalence and risk factors for cognitive impairment in patients with several common cardiac conditions: heart failure, coronary artery disease, and aortic valve stenosis. We discuss the potential effects of guideline-based treatments on cognition and identify open questions and unmet needs. Given the high prevalence of unrecognized cognitive impairment in cardiac patients, we recommend a stepwise approach to improve detection and management of cognitive impairment.

Characterization of hippocampal sclerosis of aging and its association with other neuropathologic changes and cognitive deficits in the oldest-old.

Hippocampal sclerosis of aging (HS-A) is a common age-related neuropathological lesion characterized by neuronal loss and astrogliosis in subiculum and CA1 subfield of hippocampus. HS-A is associated with cognitive decline that mimics Alzheimer's disease. Pathological diagnosis of HS-A is traditionally binary based on presence/absence of the lesion. We compared this traditional measure against our novel quantitative measure for studying the relationship between HS-A and other neuropathologies and cognitive impairment. We included 409 participants from The 90+ study with neuropathological examination and longitudinal neuropsychological assessments. In those with HS-A, we examined digitized H&E and LFB stained hippocampal slides. The length of HS-A in each subfield of hippocampus and subiculum, each further divided into three subregions, was measured using Aperio eSlide Manager. For each subregion, the proportion affected by HS-A was calculated. Using regression models, both traditional/binary and quantitative measures were used to study the relationship between HS-A and other neuropathological changes and cognitive outcomes. HS-A was present in 48 (12%) of participants and was always focal, primarily affecting CA1 (73%), followed by subiculum (9%); overlapping pathology (subiculum and CA1) affected 18% of individuals. HS-A was more common in the left (82%) than the right (25%) hemisphere and was bilateral in 7% of participants. HS-A traditional/binary assessment was associated with limbic-predominant age-related TDP-43 encephalopathy (LATE-NC; OR = 3.45, p < 0.001) and aging-related tau astrogliopathy (ARTAG; OR = 2.72, p = 0.008). In contrast, our quantitative approach showed associations between the proportion of HS-A (CA1/subiculum/combined) and LATE-NC (p = 0.001) and arteriolosclerosis (p = 0.005). While traditional binary assessment of HS-A was associated with impaired memory (OR = 2.60, p = 0.007), calculations (OR = 2.16, p = 0.027), and orientation (OR = 3.56, p < 0.001), our quantitative approach revealed additional associations with impairments in language (OR = 1.33, p = 0.018) and visuospatial domains (OR = 1.37, p = 0.006). Our novel quantitative method revealed associations between HS-A and vascular pathologies and impairment in cognitive domains that were not detected using traditional/binary measures.

Effects of intravascular photobiomodulation on cognitive impairment and crossed cerebellar diaschisis in patients with traumatic brain injury: a longitudinal study.

The association between intravascular photobiomodulation (iPBM) and crossed cerebellar diaschisis (CCD) and cognitive dysfunction in patients with traumatic brain injury (TBI) remains unknown. We postulate that iPBM might enable greater neurologic improvements. The objective of this study was to evaluate the clinical impact of iPBM on the prognosis of patients with TBI. In this longitudinal study, patients who were diagnosed with TBI were recruited. CCD was identified from brain perfusion images when the uptake difference of both cerebella was > 20%. Thus, two groups were identified: CCD( +) and CCD( -). All patients received general traditional physical therapy and three courses of iPBM (helium-neon laser illuminator, 632.8 nm). Treatment assemblies were conducted on weekdays for 2 consecutive weeks as a solitary treatment course. Three courses of iPBM were performed over 2-3 months, with 1-3 weeks of rest between each course. The outcomes were measured using the Rancho Los Amigos Levels of Cognitive Functioning (LCF) tool. The chi-square test was used to compare categorical variables. Generalized estimating equations were used to verify the associations of various effects between the two groups. p < 0.05 indicated a statistically significant difference. Thirty patients were included and classified into the CCD( +) and CCD( -) groups (n = 15, each group). Statistics showed that before iPBM, CCD in the CCD( +) group was 2.74 (exp 1.0081) times higher than that of CCD( -) group (p = 0.1632). After iPBM, the CCD was 0.64 (exp-0.4436) times lower in the CCD( +) group than in the CCD( -) group (p < 0.0001). Cognitive assessment revealed that, before iPBM, the CCD( +) group had a non-significantly 0.1030 lower LCF score than that of CCD( -) group (p = 0.1632). Similarly, the CCD( +) group had a non-significantly 0.0013 higher score than that of CCD( -) after iPBM treatment (p = 0.7041), indicating no significant differences between the CCD( +) or CCD( -) following iPBM and general physical therapy. CCD was less likely to appear in iPBM-treated patients. Additionally, iPBM was not associated with LCF score. Administration of iPBM could be applied in TBI patients to reduce the occurrence of CCD. The study failed to show differences in cognitive function after iPBM, which still serves as an alternative non-pharmacological intervention.

Multidomain modifiable dementia risk factors are associated with poorer cognition in midlife.

OBJECTIVE: Studies of modifiable dementia risk factors (MDRFs) generally consider MDRFs individually, despite strong evidence that they co-occur in adult populations. In a large sample of middle-aged adults, this study aimed to determine the frequency and co-occurrence of MDRFs, spanning five domains (mood symptomatology, risky lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology). The relationship between number of domains in which MDRFs were reported with cognitive performance and subjective cognitive concerns was then determined. METHOD: Middle-aged adults (n = 1,610) enrolled in the Healthy Brain Project and completed self-report surveys about their health and lifestyle. Participants also completed the Cogstate Brief Battery and the Cognitive Function Instrument, a measure of subjective ratings of cognition. Participants were classified according to number of domains (mood symptomatology, risky lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology) in which they reported at least one MDRF (0-5). Age, sex, education, and ethnicity were adjusted for in analyses. RESULTS: Most individuals (66.5%) reported MDRFs in two or more domains. Compared with individuals displaying no MDRFs, individuals with MDRFs in 3-5 domains showed worse learning/working memory performance and greater subjective cognitive concerns, with the magnitude of these differences moderate-to-large (d = 0.30-0.93). Individuals displaying MDRFs in five domains also showed worse attention/psychomotor function (d = 0.58) compared to those displaying no MDRFs. CONCLUSIONS: These findings may suggest that multidomain MDRFs are highly frequent in middle-aged adults and are related to poorer cognition. This supports that modifiable dementia risk is multidimensional and raises the possibility that multidomain behavioral intervention trials in middle-aged adults may be useful to delay or prevent cognitive impairment or decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cortical thickness of the left parahippocampal cortex links central hearing and cognitive performance in aging.

Hearing impairment is considered a leading modifiable risk factor of cognitive decline and dementia. While most evidence has been established on clinical assessment of peripheral hearing loss, understanding of how central hearing in real-world conditions is associated with cognitive aging is limited. This study analyzed the data of 473 unrelated healthy adults aged 36-100 years old from the Lifespan Human Connectome Project in Aging. Central hearing was evaluated using the Words-in-Noise decibel threshold. Cognitive functions were evaluated by the performance on cognitive tests, and cortical thickness was estimated from magnetic resonance imaging (MRI) data. Here, we show that a higher hearing threshold was associated with a lower performance on immediate and delayed episodic memory retrieval, switching aspect of executive function, working memory, reading decoding, and vocabulary comprehension. Cortical thickness in the left parahippocampal cortex (lPHC) was negatively associated with the hearing threshold and acted as a significant partial mediator in the association of central hearing with immediate recall, switching, reading decoding, and vocabulary comprehension. These findings suggest that cortical thickness in the lPHC, an early target of dementia, partially links central hearing and performance in multiple cognitive domains in aging.

Sex-specific effects of ethanol consumption in older Fischer 344 rats on microglial dynamics and Aß(1-42) accumulation.

Chronic alcohol consumption, Alzheimer's disease (AD), and vascular dementia are all associated with cognitive decline later in life, raising questions about whether their underlying neuropathology may share some common features. Indeed, recent evidence suggests that ethanol exposure during adolescence or intermittent drinking in young adulthood increased neuropathological markers of AD, including both tau phosphorylation and beta-amyloid (Aß) accumulation. The goal of the present study was to determine whether alcohol consumption later in life, a time when microglia and other neuroimmune processes tend to become overactive, would influence microglial clearance of Aß(1-42), focusing specifically on microglia in close proximity to the neurovasculature. To do this, male and female Fischer 344 rats were exposed to a combination of voluntary and involuntary ethanol consumption from ∼10 months of age through ∼14 months of age. Immunofluorescence revealed profound sex differences in microglial co-localization, with Aß(1-42) showing that aged female rats with a history of ethanol consumption had a higher number of iba1+ cells and marginally reduced expression of Aß(1-42), suggesting greater phagocytic activity of Aß(1-42) among females after chronic ethanol consumption later in life. Interestingly, these effects were most prominent in Iba1+ cells near neurovasculature that was stained with tomato lectin. In contrast, no significant effects of ethanol consumption were observed on any markers in males. These findings are among the first reports of a sex-specific increase in microglia-mediated phagocytosis of Aß(1-42) by perivascular microglia in aged, ethanol-consuming rats, and may have important implications for understanding mechanisms of cognitive decline associated with chronic drinking.

Case study of invalid to valid shift in cognitive performance following successful treatment of psychogenic nonepileptic seizure events.

Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient's outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.