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).

Shared and distinct structural brain alterations and cognitive features in drug-naïve schizophrenia and bipolar disorder.

Our study aimed to examine the shared and distinct structural brain alterations, including cortical thickness(CT) and local gyrification index(LGI), and cognitive impairments between the early course stage of drug-naïve schizophrenia(SZ) and bipolar disorder(BD) patients when compared to healthy controls(HCs), and to further explore the correlation between altered brain structure and cognitive impairments. We included 72 SZ patients, 35 BD patients and 43 HCs. The cognitive function was assessed using the MATRICS Consensus Cognitive Battery. Cerebral cortex analyses were performed with FreeSurfer. Furthermore, any structural aberrations related to cognition impairments were examined. Cognitive impairments existed in SZ and BD patients and were much more severe and widespread in SZ patients, compared to HCs. There were no significant differences in LGI among three groups. Compared to HCs, SZ had thicker cortex in left pars triangularis, and BD showed thinner CT in left postcentral gyrus. In addition, BD showed thinner cortex in left pars triangularis, left pars opercularis, left insula and right fusiform gyrus compared to SZ. Moreover, our results indicated that CT in many brain areas were significantly correlated with cognitive function in HCs, but only CT of left pars triangularis was correlated with impaired social cognition found in SZ. The findings suggest that changes of CT in the left pars triangularis and left postcentral gyrus may be potential pathophysiological mechanisms of the cognition impairments in SZ and BD, respectively, and the divergent CT of partly brain areas in BD vs. SZ may help distinguish them in early phases.

Hepatic encephalopathy and depression in chronic liver disease: is the common link systemic inflammation?

Hepatic encephalopathy and depression share a number of clinical features, such as cognitive impairment and psychomotor retardation, and are highly prevalent in patients with chronic liver disease. Both conditions signify a poor prognosis, carry an increased mortality and are major determinants of reduced health related quality of life. The pathophysiology of hepatic encephalopathy is complex. Whilst cerebral accumulation of ammonia is well-recognised as being central to the development of hepatic encephalopathy, systemic inflammation, which acts in synergy with hyperammonaemia, is emerging as a key driver in its development. The pro-inflammatory state is also widely documented in depression, and peripheral to brain communication occurs resulting in central inflammation, behavioural changes and depressive symptoms. Gut dysbiosis, with a similar reduction in beneficial bacteria, increase in pathogens and decreased bacterial diversity, has been observed in both hepatic encephalopathy and depression, and it may be that the resultant increased bacterial translocation causes their shared inflammatory pathophysiology. Whilst the literature on a positive association between hepatic encephalopathy and depression in cirrhosis remains to be substantiated, there is evolving evidence that treatment with psychobiotics may be of dual benefit, improving cognition and mood in cirrhosis.

Investigating Neurophysiological Markers of Symptom Severity in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by a progressive decline in cognitive functioning for which there is a stark lack of effective treatments. Investigating the neurophysiological markers of symptom severity in AD may aid in the identification of alternative treatment targets. OBJECTIVE: In the current study we used a multimodal approach to investigate the association between functional connectivity (specifically between scalp electrodes placed over frontal and parietal regions) and symptom severity in AD, and to explore the relationship between connectivity and cortical excitability. METHODS: 40 people with AD (25 mild severity, 15 moderate severity) underwent neurobiological assessment (resting state electroencephalography (EEG) and prefrontal transcranial magnetic stimulation (TMS) with EEG) and cognitive assessment. Neurobiological outcomes were resting state functional connectivity and TMS-evoked potentials. Cognitive outcomes were scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, and a measure of episodic verbal learning. RESULTS: Greater contralateral functional theta connectivity between frontal scalp electrodes and parietal scalp electrodes was associated with poorer cognitive performance. In addition, significant correlations were seen between the contralateral theta connectivity and the N100 and P60 TMS-evoked potentials measured from electrodes over the left dorsolateral prefrontal cortex. CONCLUSION: Together these findings provide initial support for the use of multimodal neurophysiological approaches to investigate potential therapeutic targets in AD. Suggestions for future research are discussed.

Cardiac autonomic function and cognitive performance in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with loss of cognition and dementia. Cardiac autonomic dysfunction has been linked to cognitive decline. We aimed to investigate if reduced cardiac autonomic function (CAF) is associated with cognitive impairment in AF patients. METHODS: Patients with paroxysmal, persistent and permanent AF were enrolled from a multicenter cohort study if they had AF ("AF group") or sinus rhythm ("SR group") on a baseline 5 min ECG recording. Parameters quantifying CAF (heart rate variability triangular index (HRVI), mean heart rate (MHR), RMSSD, SDNN, total power and power in the VLF, LF, HF ranges) were calculated. We used the Montreal Cognitive Assessment (MoCA) to assess global cognitive function. RESULTS: 1685 AF patients with a mean age of 73 ± 8 years, 29% females, were included. MoCA score was 24.5 ± 3.2 in the AF group (N = 710 patients) and 25.4 ± 3.2 in the SR group (N = 975 patients). After adjusting for multiple confounders, lower HRVI was associated with lower MoCA scores, both in the SR group [ß = 0.049; 95% confidence interval (CI) 0.016-0.081; p = 0.003] and in the AF group (ß = 0.068; 95% CI 0.020-0.116; p = 0.006). In the AF group, higher MHR was associated with a poorer performance in the MoCA (ß = - 0.008; 95% CI - 0.014 to - 0.002; p = 0.014). We found no convincing evidence of association for other CAF parameters with cognition. CONCLUSION: Our data suggest that impaired CAF is associated with worse cognitive performance in patients with AF. Among standard HRV parameters, HRVI might be the most promising ECG index. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02105844.

Modafinil rescues repeated morphine-induced synaptic and behavioural impairments via activation of D1R-ERK-CREB pathway in medial prefrontal cortex.

Long-term opioid abuse causes a variety of long-lasting cognitive impairments such as attention, impulsivity and working memory. These cognitive impairments undermine behavioural treatment for drug abuse and lead to poor treatment retention and outcomes. Modafinil is a wake-promoting drug that shows potential in improving attention and memory in humans and animals. However, modafinil's effect on opioid-induced cognitive impairments remains unclear, and the underlying mechanism is poorly understood. This study showed that repeated morphine administration significantly impairs attention, increases impulsivity and reduces motivation to natural rewards in mice. Systemic modafinil treatment at low dose efficiently ameliorates morphine-induced attention dysfunction and improves motivation and working memory in mice. High dose of modafinil has adverse effects on impulsive action and attention. Local infusion of D1R antagonist SCH-23390 reverses the morphine-induced synaptic abnormalities and activation of the D1R-ERK-CREB pathway in medial prefrontal cortex (mPFC). This study demonstrated a protective effect of modafinil in mPFC neurons and offered a therapeutic potential for cognitive deficits in opioid abuse.

An altered balance of integrated and segregated brain activity is a marker of cognitive deficits following sleep deprivation.

Sleep deprivation (SD) leads to impairments in cognitive function. Here, we tested the hypothesis that cognitive changes in the sleep-deprived brain can be explained by information processing within and between large-scale cortical networks. We acquired functional magnetic resonance imaging (fMRI) scans of 20 healthy volunteers during attention and executive tasks following a regular night of sleep, a night of SD, and a recovery nap containing nonrapid eye movement (NREM) sleep. Overall, SD was associated with increased cortex-wide functional integration, driven by a rise of integration within cortical networks. The ratio of within versus between network integration in the cortex increased further in the recovery nap, suggesting that prolonged wakefulness drives the cortex towards a state resembling sleep. This balance of integration and segregation in the sleep-deprived state was tightly associated with deficits in cognitive performance. This was a distinct and better marker of cognitive impairment than conventional indicators of homeostatic sleep pressure, as well as the pronounced thalamocortical connectivity changes that occurs towards falling asleep. Importantly, restoration of the balance between segregation and integration of cortical activity was also related to performance recovery after the nap, demonstrating a bidirectional effect. These results demonstrate that intra- and interindividual differences in cortical network integration and segregation during task performance may play a critical role in vulnerability to cognitive impairment in the sleep-deprived state.

Chronic alcohol exposure during critical developmental periods differentially impacts persistence of deficits in cognitive flexibility and related circuitry.

Cognitive flexibility in decision making depends on prefrontal cortical function and is used by individuals to adapt to environmental changes in circumstances. Cognitive flexibility can be measured in the laboratory using a variety of discrete, translational tasks, including those that involve reversal learning and/or set-shifting ability. Distinct components of flexible behavior rely upon overlapping brain circuits, including different prefrontal substructures that have separable impacts on decision making. Cognitive flexibility is impaired after chronic alcohol exposure, particularly during development when the brain undergoes rapid maturation. This review examines how cognitive flexibility, as indexed by reversal and set-shifting tasks, is impacted by chronic alcohol exposure in adulthood, adolescent, and prenatal periods in humans and animal models. We also discuss areas for future study, including mechanisms that may contribute to the persistence of cognitive deficits after developmental alcohol exposure and the compacting consequences from exposure across multiple critical periods.

Cognitive Deficit in Schizophrenia: From Etiology to Novel Treatments.

Schizophrenia is a major mental illness characterized by positive and negative symptoms, and by cognitive deficit. Although cognitive impairment is disabling for patients, it has been largely neglected in the treatment of schizophrenia. There are several reasons for this lack of treatments for cognitive deficit, but the complexity of its etiology-in which neuroanatomic, biochemical and genetic factors concur-has contributed to the lack of effective treatments. In the last few years, there have been several attempts to develop novel drugs for the treatment of cognitive impairment in schizophrenia. Despite these efforts, little progress has been made. The latest findings point to the importance of developing personalized treatments for schizophrenia which enhance neuroplasticity, and of combining pharmacological treatments with non-pharmacological measures.

Basic and complex cognitive functions in Adult ADHD.

BACKGROUND: Many clinical studies reported deficits in basic and complex cognitive functions in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the extent in which deficits in basic functions (i.e., processing speed and distractibility) contribute to complex cognitive impairments (i.e., working memory, planning, cognitive flexibility, memory functions) in adults with ADHD is not well-studied. So far, literature show only one study, revealing that basic functions explain 27-74% of executive dysfunctions. Yet, the authors reported that findings could be affected by the selection of neuropsychological tests. The goal of the present research is to replicate such a finding using a different sample and a different set of neuropsychological tests. METHODS: Forty-eight adult patients with ADHD were compared with 48 healthy controls in basic cognitive functions, namely processing speed and distractibility and more complex cognitive functions, namely selective attention, cognitive flexibility, planning, working memory, verbal fluency, and verbal memory. Basic and complex cognitive functions were assessed using the Vigilance and Sustained Attention, Selective Attention, N-Back, Tower of London, Trail Making Test, Word Fluency, and Verbal Learning and Memory. RESULTS AND CONCLUSION: Logistic regression analyses showed that impairments in complex cognitive functions explained 25% of the variance in ADHD diagnosis. The explained variance dropped from 25% to 9% after considering basic functions of processing speed and distractibility. This 64% reduction highlights the importance of basic functions for impairments in complex functions in patients with ADHD.

Current findings and perspectives on aberrant neural oscillations in schizophrenia.

There is now consistent evidence that neural oscillation at low- and high-frequencies constitute an important aspect of the pathophysiology of schizophrenia. Specifically, impaired rhythmic activity may underlie the deficit to generate coherent cognition and behavior, leading to the characteristic symptoms of psychosis and cognitive deficits. Importantly, the generating mechanisms of neural oscillations are relatively well-understood and thus enable the targeted search for the underlying circuit impairments and novel treatment targets. In the following review, we will summarize and assess the evidence for aberrant rhythmic activity in schizophrenia through evaluating studies that have utilized Electro/Magnetoencephalography to examine neural oscillations during sensory and cognitive tasks as well as during resting-state measurements. These data will be linked to current evidence from post-mortem, neuroimaging, genetics, and animal models that have implicated deficits in GABAergic interneurons and glutamatergic neurotransmission in oscillatory deficits in schizophrenia. Finally, we will highlight methodological and analytical challenges as well as provide recommendations for future research.

Association Between Cognitive Trajectories and Disability Progression in Patients With Relapsing-Remitting Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Longitudinal cognitive trajectories in multiple sclerosis are heterogeneous and difficult to measure. We aimed to identify discrete longitudinal reaction time trajectories in relapsing-remitting multiple sclerosis using a computerized cognitive battery and to assess the association between trajectories of reaction time and disability progression. METHODS: All participants serially completed computerized reaction time tasks measuring psychomotor speed, visual attention, and working memory. Participants completed at least 3 testing sessions over a minimum of 180 days. Longitudinal reaction times were modeled with latent class mixed models to identify groups of individuals sharing similar latent characteristics. Optimal models were validated for consistency and baseline associations with class membership tested using multinomial logistic regression. Interclass differences in the probability of reaction time worsening and the probability of 6-month confirmed disability progression were assessed with survival analysis. RESULTS: A total of 460 people with relapsing-remitting multiple sclerosis were included in the analysis. For each task of the MSReactor battery, the optimal model comprised 3 latent classes. All MSReactor tasks could identify a group with high probability of reaction time slowing. The visual attention and working memory tasks could identify a group of participants who were 3.7 and 2.6 times more likely to experience a 6-month confirmed disability progression, respectively. Participants could be classified into predicted cognitive trajectories after just 5 tests with 64% to 89% accuracy. DISCUSSION: Latent class modeling of longitudinal cognitive data collected by a computerized battery identified patients with worsening reaction times and increased risk of disability progression. Slower baseline reaction time, age, and disability increased assignment into this trajectory. Monitoring of cognition in clinical practice with computerized tests may enable detection of cognitive change trajectories and people with relapsing-remitting multiple sclerosis at risk of disability progression.

Effects and Mechanisms of Synaptotagmin-7 in the Hippocampus on Cognitive Impairment in Aging Mice.

Aging is an irreversible biological process that involves oxidative stress, neuroinflammation, and apoptosis, and eventually leads to cognitive dysfunction. However, the underlying mechanisms are not fully understood. In this study, we investigated the role and potential mechanisms of Synaptotagmin-7, a calcium membrane transporter in cognitive impairment in aging mice. Our results indicated that Synaptotagmin-7 expression significantly decreased in the hippocampus of D-galactose-induced or naturally aging mice when compared with healthy controls, as detected by western blot and quantitative reverse transcriptase-polymerase chain reaction analysis. Synaptotagmin-7 overexpression in the dorsal CA1 of the hippocampus reversed long-term potentiation and improved hippocampus-dependent spatial learning in D-galactose-induced aging mice. Synaptotagmin-7 overexpression also led to fully preserved learning and memory in 6-month-old mice. Mechanistically, we demonstrated that Synaptotagmin-7 improved learning and memory by elevating the level of fEPSP and downregulating the expression of aging-related genes such as p53 and p16. The results of our study provide new insights into the role of Synaptotagmin-7 in improving neuronal function and overcoming memory impairment caused by aging, suggesting that Synaptotagmin-7 overexpression may be an innovative therapeutic strategy for treating cognitive impairment.

Evidence of residual cognitive deficits in young adults with a concussion history from adolescence.

The present study investigated executive function and sustained attention of non-athlete, young adults (ages 18-23) with a history of concussion beyond ten months post incident. Cognitive functioning was examined in 24 non-athletic, college students with a concussion history (mean age 21 yrs.; mean time and range post-injury: 4 years, 10-90 months) and 24 non-athletic controls with no history (NH) of concussion. Computerized versions of two cognitive assessment techniques were utilized to examine executive functioning (Stroop) and sustained attention capacity (D2). Primary dependent variables were response time, error score, and sustained attention score. Relationships between dependent variables and concussion metrics were also analyzed. ANOVA's revealed a significantly higher error rate in concussion history (CH) participants when performing the Stroop task (p < 0.05), including a trend for greater errors in the incongruent task condition (p < 0.05). Group measures did not differ in the sustained attention test (all p > 0.05). Nevertheless, there was a significant relationship between D2 error rate and time since concussion (p < 0.01), showing that D2 error rate was greater for participants with more time since concussion sustainment. Our findings indicate the potential for prolonged cognitive dysfunction linked to decision-making, but not to processing speed, in young adult non-athletes with a CH averaging four years post-injury. These findings may provide evidence of residual cognitive deficits in young adults with a concussion history over time.

Impaired cerebral blood flow regulation and cognition in male football players.

Football players are at increased risk of neurodegeneration, the likely consequence of repetitive mechanical trauma caused by heading the ball. However, to what extent a history of heading the ball affects cerebral blood flow (CBF) regulation and its potential relationship to cognitive impairment is unknown. To address this, we recruited 16 concussion-free male amateur football players (age: 25 ± 6 y) with a history of heading the ball (18 ± 6 y) and 18 sex, age, education, and activity-matched controls with no prior history of contact sport participation or concussion. Cerebral perfusion was measured at rest and in response to both hyper/hypocapnia to determine cerebrovascular reactivity to carbon dioxide (CVRCO2HYPER/HYPO ) using transcranial Doppler ultrasound and capnography, with the sum reflecting the cerebral vasomotor range. Cognition and visuomotor coordination were assessed using the Montreal cognitive assessment (MoCA) and the Grooved Pegboard Dexterity Test (GPD), respectively. While no differences in cerebral perfusion were observed (p = 0.938), CVRCO2HYPER/HYPO (p = 0.038/p = 0.025), cerebral vasomotor range (p = 0.002), MoCA (p = 0.027), and GPD performance (dominant hand, P ≤ 0.001) were consistently lower in the players compared to controls. These findings are the first to demonstrate that CBF regulation and cognition are collectively impaired in male football players with history of heading the ball, which may contribute to neurodegeneration.

Electrophysiological Evidence of Auditory and Cognitive Processing Deficits in Parkinson Disease.

BACKGROUND: Parkinson's disease (PD) patients are at increased risk for central auditory processing (CAP) deficits and cognitive dysfunction. However, behavioral assessments of CAP and cognitive processing used in a previous study by our research team found few significant differences in performance between early-stage PD patients and age-matched control subjects. The objective of this study is to use auditory event-related potentials (AERPs) to compare CAP and cognitive functions in a population of PD patients with a group of age-matched control subjects. METHODS: AERPs in response to tonal and speech stimuli were recorded from 35 adults who had a medical diagnosis of PD (23 males and 12 females; mean age = 66.9 ± s.d.11.2 years), and 35 age-matched control subjects who did not have PD or any other neurological disorders (31 males and 4 females; mean age = 65.4 ± s.d.12.3 years). Auditory stimuli included pure tones (500 and 1000 Hz) to elicit the P300 response and a dichotic digits paradigm to elicit the N200 processing negativity. RESULTS: Compared to control subjects, PD patients exhibited significantly longer latencies of P300 and N200 components and smaller amplitude N200 components. Latency and amplitude of the N200 component were significantly correlated with participants' age. N200 amplitude was correlated with results from the Rey Auditory Verbal Learning Test (RAVLT) of cognitive ability. Latency of the P300 and amplitude of the N200 components were significantly correlated with results from the Spatial Release From Masking (SRM) behavioral CAP assessment. CONCLUSIONS: AERP assessments used in this study appear to be sensitive indicators of CAP and cognitive deficits exhibited by early-stage PD patients. While few significant differences in performance on behavioral CAP and cognitive tests were previously observed between this population of PD patients and age-matched control subjects, N200 and P300 components recorded in the present study revealed impaired neural processing by the PD group.

Early developmental impact of sex chromosome trisomies on attention deficit-hyperactivity disorder symptomology in young children.

Individuals with sex chromosome trisomies ([SCT], XXX, XXY, and XYY)) are at increased risk for neurodevelopmental problems, given that a significant portion of the sex chromosome genes impact brain functioning. An elevated risk for psychopathology has also been described, including attention deficit-hyperactivity disorder (ADHD). The present study aimed at identifying early markers of ADHD, providing the first investigation of ADHD symptomology in very young children with SCT. The variety, type, and severity of ADHD symptomology in 1-6-year-old children with SCT (n = 104) were compared with population-based controls (n = 101) using the strengths and weaknesses of ADHD symptoms and normal-behavior (SWAN) parent-report questionnaire. ADHD symptomology was significantly more prevalent in SCT and already present from toddlerhood on, compared to controls. ADHD inattention symptoms were significantly increased in all karyotypes (XXX, XXY, and XYY), boys with XYY also showed significantly more hyperactivity/impulsivity symptoms than controls. Inattentiveness was more pronounced with increasing age for SCT, in contrast to controls. Within the SCT group, 24% of the children had significantly elevated ADHD symptoms at a clinical level. Already from an early age on, SCT is associated with a risk for ADHD, suggesting that its neurodevelopmental risk lies anchored in early brain maturation. Studying this genetically vulnerable population allows for the prospective study of risk markers to facilitate early and preventive interventions.

Obstructive Sleep Apnea: Cognitive Outcomes.

There is a strong association between obstructive sleep apnea (OSA) and cognitive dysfunction. Executive function, attention, verbal/visual long-term memory, visuospatial/constructional ability, and information processing are more likely to be affected, whereas language, psychomotor function, and short-term memory are less likely to be affected. Increased accumulation of Aß2-amyloid in the brain, episodic hypoxemia, oxidative stress, vascular inflammation, and systemic comorbidities may contribute to the pathogenesis. Patients with OSA should have cognitive screening or formal testing, and patients with cognitive decline should have testing for OSA. Treatment with continuous positive airway pressure may improve cognitive symptoms in the patient with OSA.

Epigallocatechin-3-Gallate Provides Protection Against Alzheimer's Disease-Induced Learning and Memory Impairments in Rats.

PURPOSE: Recent evidence has highlighted the anti-inflammatory properties of the constituent of Green Tea Polyphenols (GTP), epigallocatechin-3-gallate (EGCG) which has been suggested to exert a neuroprotective effect on Alzheimer's disease (AD). The current study aimed to elucidate the effect of EGCG on memory function in rats with AD. METHODS: AD rat models were initially established through an injection with Aß 25-35 solution, followed by gavage with EGCG at varying doses to determine the effect of EGCG on learning and cognitive deficits in AD. Morris water maze test was conducted to evaluate the spatial memory function of the rats. Immunohistochemistry and Western blot analysis were performed to identify Tau phosphorylation. The expression of ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA and protein in rat hippocampus was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Acetylcholinesterase (AchE) activity, Aß1-42 expression and Ach content were all detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: EGCG intervention brought about a decrease in the escape latency period while increasing the time at the target quadrant among the AD rats. EGCG decreased the hyperphosphorylation of Tau in hippocampus. BACE1 expression and activity as well as the expression of Aß1-42 were suppressed by EGCG. Moreover, EGCG promoted Ach content by diminishing the activity of AchE. CONCLUSION: The current study demonstrates that EGCG may diminish the hyperphosphorylation of the Tau protein, downregulate BACE1 and Aß1-42 expression to improve the antioxidant system and learning and memory function of rats with AD.