Treatment of 95 post-Covid patients with SSRIs.

After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs). This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response. Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia. Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge. Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS. The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.

Predictors of long-term health-related quality of life in Guillain-Barré syndrome: A hospital-based study.

OBJECTIVE: This study aimed to determine the impact of patients' baseline clinical, neurophysiological data, and management plan of Guillain-Barré syndrome (GBS) on long-term quality of life (QoL) and to identify its potential predictors. METHODS: Seventy-nine GBS patients were recruited. On admission, participants were evaluated using the Medical Research Council (MRC) sumscore, GBS disability scale (GDS), and Erasmus GBS Respiratory Insufficiency Score (EGRIS). Neurophysiological data were collected, and a management plan was devised. MRC sumscore was repeated at nadir. MRC, GDS and Short Form Survey (SF-36) were assessed at first-year follow-up. RESULTS: The mean age was 37.84 ± 17.26 years, with 43 male patients (54.4%). QoL at one year correlated significantly with baseline clinical variables (age, number of days between weakness and admission, MRC sumscore at onset and nadir, high GDS, and EGRIS scores). Antecedent events, especially diarrhoea, neck muscle weakness, autonomic dysfunction, cranial nerve involvement, and mechanical ventilation (MV), associated with worse QoL. Axonal GBS patients had lower QoL than AIDP patients, and PE patients exhibited lower QoL than IVIG patients. Multiple regression analysis showed that older age, diarrhoea, number of days between weakness and admission, neck muscle weakness, cranial nerve involvement, autonomic dysfunction, early MV, and MRC at onset and nadir and high GDS could predict poor QoL. CONCLUSION: Older age, more days between weakness and admission, neck muscle weakness, cranial nerve involvement, autonomic dysfunction, early MV, diarrhoea, low MRC at onset and nadir, high GDS at onset, axonal type, and PE treatment were potential predictors of poor QoL in GBS.

An analysis of neuropathic pain, vasomotor manifestations, and sympathetic skin reactions in post-COVID-19 patients relative to healthy individuals.

This study aims to assess the incidence of neuropathic pain, vasomotor symptoms, and sympathetic skin responses (SSR) in patients who have recovered from COVID-19 infection and contrast these findings with healthy controls. The study encompassed 56 post-COVID-19 patients and 40 healthy controls (group 1: post-COVID-19 patients, and group 2: healthy controls). The presence of autonomic dysfunction symptoms (ADS) and orthostatic hypotension following COVID-19 infection was documented in group 1. Concurrently, fatigue and forgetfulness levels were appraised using the numerical rating scale, and the leeds assessment of neuropathic symptoms and signs pain scale was deployed to probe for the incidence of neuropathic pain among participants. SSR of all participants was conducted bilaterally from median and tibial nerves using an electroneuromyographic device. Among post-COVID-19 patients, neuropathic pain was observed in 17.9% of cases. There were no notable variations in the initiation and magnitude of bilateral median and tibial nerve SSR across the 2 groups. Significant discrepancies were observed in ADS scores between groups 1 and 2 (P = .001). Furthermore, a positive correlation was established between the latencies of the left median nerve SSR and ADS scores (R = 0.339, P = .014). The SSR patterns were congruous between healthy individuals and post-COVID-19 patients. However, a higher prevalence of autonomic dysfunction symptoms and correlations among SSR, autonomic dysfunction scores, fatigue, and forgetfulness levels were identified among post-COVID-19 patients.

Dysautonomia, Hypermobility Spectrum Disorders and Mast Cell Activation Syndrome as Migraine Comorbidities.

PURPOSE OF REVIEW: Dysautonomia refers to the dysfunction of the autonomic nervous system and encompasses a wide variety of autonomic symptoms and disorders. The most common autonomic disorders are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be encountered in clinical practice as part of a triad of dysautonomia, hypermobility spectrum disorders (HSD), and mast cell activation syndrome (MCAS). Migraine is one of the most common comorbidities of POTS, HSD, and MCAS; conversely, these conditions are also prevalent in patients with migraine, especially in those with multiple systemic symptoms, such as chronic dizziness, lightheadedness, orthostatic intolerance, joint pain, and allergic symptoms. Diagnostic criteria, pathophysiologic mechanisms, and therapeutic considerations in patients with migraine and comorbid dysautonomia, HSD, and MCAS are reviewed. RECENT FINDINGS: Numerous studies indicate a significant overlap and shared pathophysiology in migraine, dysautonomia, HSD, and MCAS. In clinical setting, dysautonomia, HSD, and MCAS may present a diagnostic and therapeutic challenge in patients with migraine and require a high index of suspicion on the part of the neurologist. Diagnosis and treatment of these complex disorders in patients with migraine is essential to comprehensive patient-centric care, reduced symptom burden, and improved functional impairment secondary to both migraine and comorbidities.

Delayed blood pressure recovery after exercise stress test is associated with autonomic dysfunction and pulse pressure in a middle-aged healthy group.

BACKGROUND: Delayed heart rate (HR) and blood pressure recovery after exercise test is known as the reliable indexes of autonomic dysfunction. Here we tried to evaluate the serial changes in various indicators during exercise test and correlations with recovery of HR and blood pressure in a normotensive healthy middle-aged group. METHODS: A total of 122 patients without hypertension or diabetes was enrolled (mean age, 55.6 ± 11.0; male, 56.6%; mean blood pressure, 124.8 ± 16.6 / 81.5 ± 9.6 mmHg). Treadmill test was performed for evaluation of chest pain. Patients with coronary artery disease, positive treadmill test result, left ventricular dysfunction or renal failure were excluded. Heart rate recovery was calculated by subtracting the HR in the first or second minute of recovery period from the HR of peak exercise (HRR1 or HRR2). Systolic blood pressure in the 4th minute of recovery stage (SBPR4) was used to show delayed blood pressure recovery. RESULTS: Metabolic equivalents (METs) and HR in stage 2 to 4 were significantly correlated with both HRR1 and HRR2. Multiple regression analysis of HRR revealed significant correlation of METs and SBPR4. SBPR4 was significantly correlated with both HRR1 and HRR2 (HRR1, r = -0.376, p<0.001; HRR2, r = -0.244, p = 0.008) as well as SBP in the baseline to stage 3 and pulse pressure (r = 0.406, p<0.001). CONCLUSIONS: Delayed BP recovery after peak exercise test revealed significant association with autonomic dysfunction and increased pulse pressure in normotensive middle-aged healthy group. It can be a simple and useful marker of autonomic dysfunction and arterial stiffness.

Dysautonomia in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized in its typical presentation by a combination of lower and upper motor neuron symptoms, with a progressive course and fatal outcome. Due to increased recognition of the non-motor symptoms, it is currently considered a multisystem disorder with great heterogeneity, regarding genetical, clinical, and neuropathological features. Often underestimated, autonomic signs and symptoms have been described in patients with ALS, and various method analyses have been used to assess autonomic nervous system involvement. The aim of this paper is to offer a narrative literature review on autonomic disturbances in ALS, based on the scarce data available to date.

Cardiac Autonomic Dysfunction and Risk of Silent Myocardial Infarction Among Adults With Type 2 Diabetes.

Background There is a paucity of large-scale epidemiological studies on the link between cardiac autonomic neuropathy (CAN) and the risk of silent myocardial infarction (SMI) in type 2 diabetes. We evaluated the association between CAN and the risk of SMI in a large sample of adults with type 2 diabetes. Methods and Results Participants with type 2 diabetes from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without atherosclerotic cardiovascular disease at baseline were included. CAN was ascertained using heart rate variability indices calculated from 10-s resting electrocardiograms. The heart rate variability indices included standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals. CAN was defined as both the standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals less than the fifth percentile of the general population. We used Cox proportional hazards regression to generate hazard ratios (HRs) for incident SMI in relation to CAN measures. Among 4842 participants (mean age, 62.5 years; 46.6% women; 60.2% White), there were 73 incident SMI cases over a median follow-up of 4.9 years (incidence rate 3.1 out of 1000 person-years [95% CI, 2.5-3.9]). After adjusting for confounders, low heart rate variability was associated with a higher risk of SMI (HR, 1.67 [95% CI, 1.02-2.72] and HR, 1.56 [95% CI, 0.94-2.58] for low standard deviation of all normal-to-normal R-R intervals and root mean square of successive differences between normal-to-normal R-R intervals, respectively). Participants with CAN had a 1.9-fold greater risk of SMI (HR, 1.91 [95% CI, 1.14-3.20]). Conclusions In a large cohort of adults with type 2 diabetes, CAN was significantly associated with an increased risk of incident SMI.

Autonomic function and motor subtypes in Parkinson's disease: a multicentre cross-sectional study.

Autonomic symptoms (AS) are critical in Parkinson's disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about incidence of AS, and examine AS profiles among PD patients by motor subtype and its relation to AS. The cross-sectional data of a multicentre sample, including 714 PD patients and 194 healthy controls from Parkinson's Progression Marker Initiative study and Pingchan granule study were analyzed, stratified by PD subtypes [postural instability and gait disturbances (PIGD), tremor dominant (TD), and indeterminate] and domain autonomic dysfunction. Compared with healthy controls, PD patients scored higher in the total Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction score and in several domain scores in particular, and there was a significant overlap in domain AS. Risk factors of individual domain autonomic dysfunction were heterogeneous. PIGD and indeterminate were the predominant subtypes in pupillomotor and thermoregulatory symptoms. TD and indeterminate were more likely to suffer from cardiovascular problem. The odd in sexual dysfunction was significant for PIGD. Gastrointestinal and urinary symptoms seemed not to be associated with a specific subtype. Our study demonstrated that AS were highly heterogeneous and 3 subtypes differed in autonomic performance, providing clues to understand mechanisms underlying AS in PD.

Autonomic dysregulation in long-term patients suffering from Post-COVID-19 Syndrome assessed by heart rate variability.

Post-COVID-19 Syndrome (PCS) is a condition with multiple symptoms partly related to dysregulation of the autonomic nerve system. Assessment of heart rate variability (HRV) using 24 h Holter-ECG may serve as a surrogate to characterize cardiac autonomic activity. A prospective study including 103 PCS patients (time after infection = 252 days, age = 49.0 ± 11.3 years, 45.7% women) was performed and patients underwent detailed clinical screening, cardiopulmonary exercise testing, and 24 h Holter monitoring. Data of PCS patients was compared to 103 CAD patients and a healthy control group (n = 90). After correction for age and sex, frequency-related variables differed in PCS patients compared to controls including LF/HFpower, LF/HFnu, and LF/HF ratio (24 h; p ≤ 0.001). By contrast, these variables were largely comparable between PCS and CAD patients, while sympathetic activation was highest in PCS patients during the 24 h period. Overall, PCS patients showed disturbed diurnal adjustment of HRV, with impaired parasympathetic activity at night. Patients hospitalized during acute infection showed an even more pronounced overactivation of sympathetic activity compared to patients who underwent ambulant care. Our data demonstrate persistent HRV alterations in PCS patients with long-term symptom duration, suggesting a sustained impairment of sympathovagal balance. Moreover, sympathetic overstimulation and diminished parasympathetic response in long-term PCS patients are comparable to findings in CAD patients. Whether HRV variables have a prognostic value in PCS and/or might serve as biomarkers indicating a successful interventional approach warrants further longitudinal studies.

Exploration of the clinical course and longitudinal correlations in frozen shoulder: The role of autonomic function, central pain processing, and psychological variables. A longitudinal multicenter prospective observational study.

BACKGROUND: Altered central pain processing (CPP) and dysautonomia might play a role in the clinical course of frozen shoulder and psychological factors, like pain catastrophizing and hypervigilance, might influence clinical variables in frozen shoulder. OBJECTIVES: To explore the clinical course of frozen shoulder regarding CPP, dysautonomia, pain catastrophizing, and hypervigilance and to explore whether longitudinal correlations between these outcomes and pain intensity were present. DESIGN: prospective longitudinal observational study. METHOD: Participants with frozen shoulder were recruited at hospitals and general practitioner practices and followed for 9 months. They completed six questionnaires (about demographics, shoulder pain and disability, pain intensity, pain catastrophizing, pain hypervigilance, and autonomic symptoms) and underwent tactile sensitivity (allodynia), pressure pain thresholds (hyperalgesia), temporal summation, and conditioned pain modulation during four timeframes (3-month intervals). RESULTS: Initially, 149 participants with frozen shoulder were recruited and 88 completed all the measurements. An improvement from baseline to at least one follow-up measurement was found for shoulder pain and disability, pain intensity, pain catastrophizing, hypervigilance, and dysautonomia. A fair longitudinal correlation was found between pain intensity and catastrophizing and hypervigilance (r = 0.301-0.397). Poor longitudinal correlations were found between pain intensity and allodynia and hyperalgesia (r = -0.180-0.193), between pain catastrophizing and dysautonomia (r = 0.209) and between hypervigilance and hyperalgesia (r = -0.159). CONCLUSION: Patients with frozen shoulder showed an early improvement that flattened with time in several pain and psychological variables over the course of 9 months. However, autonomic symptoms rather showed a late improvement over 9 months.

Unveiling the role of cerebellar alterations in the autonomic nervous system: a systematic review of autonomic dysfunction in spinocerebellar ataxias.

BACKGROUND: Autonomic dysfunctions are prevalent in several cerebellar disorders, but they have not been systematically investigated in spinocerebellar ataxias (SCAs). Studies investigating autonomic deficits in SCAs are fragmented, with each one focusing on different autonomic dysfunctions and different SCA subtypes. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a systematic review of the literature to assess the presence of autonomic dysfunctions in various SCAs. PubMed served as the primary database, and the Rayyan web application was employed for study screening. RESULTS: We identified 46 articles investigating at least one autonomic function in patients with SCA. The results were analyzed and categorized based on the genetic subtype of SCA, thereby characterizing the specific autonomic deficits associated with each subtype. CONCLUSION: This review confirms the presence of autonomic dysfunctions in various genetic subtypes of SCA, underscoring the cerebellum's role in the autonomic nervous system (ANS). It also emphasizes the importance of investigating these functions in clinical practice.

Pro-arrhythmic role of adrenergic spatial densities in the human atria: An in-silico study.

Chronic stress among young patients (≤ 45 years old) could result in autonomic dysfunction. Autonomic dysfunction could be exhibited via sympathetic hyperactivity, sympathetic nerve sprouting, and diffuse adrenergic stimulation in the atria. Adrenergic spatial densities could alter atrial electrophysiology and increase arrhythmic susceptibility. Therefore, we examined the role of adrenergic spatial densities in creating arrhythmogenic substrates in silico. We simulated three 25 cm2 atrial sheets with varying adrenergic spatial densities (ASD), activation rates, and external transmembrane currents. We measured their effects on spatial and temporal heterogeneity of action potential durations (APD) at 50% and 20%. Increasing ASD shortens overall APD, and maximum spatial heterogeneity (31%) is achieved at 15% ASD. The addition of a few (5% to 10%) adrenergic elements decreases the excitation threshold, below 18 µA/cm2, while ASDs greater than 10% increase their excitation threshold up to 22 µA/cm2. Increase in ASD during rapid activation increases APD50 and APD20 by 21% and 41%, respectively. Activation times of captured beats during rapid activation could change by as much as 120 ms from the baseline cycle length. Rapidly activated atrial sheets with high ASDs significantly increase temporal heterogeneity of APD50 and APD20. Rapidly activated atrial sheets with 10% ASD have a high likelihood (0.7 ± 0.06) of fragmenting otherwise uniform wavefronts due to the transient inexcitability of adrenergically stimulated elements, producing an effective functional block. The likelihood of wave fragmentation due to ASD highly correlates with the spatial variations of APD20 (ρ = 0.90, p = 0.04). Our simulations provide a novel insight into the contributions of ASD to spatial and temporal heterogeneities of APDs, changes in excitation thresholds, and a potential explanation for wave fragmentation in the human atria due to sympathetic hyperactivity. Our work may aid in elucidating an electrophysiological link to arrhythmia initiation due to chronic stress among young patients.

Gender differences in non-motor fluctuations in Parkinson's disease.

Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the study is to estimate the burden of NMF in PD patients and to evaluate the possible gender effect. PD patients fulfilling the MDS-PD diagnostic criteria attending the "Parkinson's Disease and Movement Disorders Centre" of the University of Catania were evaluated using the Non-Motor Fluctuations Assessment (NoMoFA) Questionnaire. NoMoFA items were also grouped into the following domains: cognitive, mood, sleep/fatigue, dysautonomia, hallucination/perception and miscellaneous domains were identified. One-hundred and twenty-one patients with PD (67 men, 55.4%; mean age 70.2 ± 8.9 years, disease duration 8.3 ± 4.6 years) were evaluated. All PD patients reported at least one NMS, whereas 87 (71.9%) also reported NMF. "Feel sluggish or had low energy levels" (47.2%) along with "Feel excessively sleepy during the day" (40.0%) were the most common NMF reported in the whole sample. The majority of PD patients reported the presence of NMF during the OFF state (79, 65.3%). At multivariate analysis, NMF were positively associated with the female gender (adjusted OR 3.13; 95%CI 1.21-8.11 p-value 0.01). Women with PD had higher NMF scores especially in depression/anxiety, sleep/fatigue and dysautonomia domains. Our study reported the presence of a gender-related pattern in the frequency of NMS and NMF in PD patients, with female gender associated with a higher risk of developing NMF, highlighting the need for personalized treatment strategies when addressing NMF.

Sudomotor deficits in Parkinson's disease with special reference to motor subtypes.

INTRODUCTION: Parkinson's disease which shows clinically heterogeneous motor derangement may also accompany various autonomic disorders, but results of previous research on incidence and degree of each autonomic dysfunction have been inconsistent. As for sudomotor dysfunction, some investigators emphasize hypo- or anhidrois, whereas others stress hyperhidrosis. SUBJECTS AND METHODS: To elucidate sudomotor dysfunctions in Parkinson's disease (PD) with respect to subtypes, 225 clinically probable patients PD patients were stratified by motor phenotype (tremor-dominant group: 33; mixed group: 105; and akinesia-rigidity group: 87) and subjected to thermal and acetylcholine-induced (focal) sweating tests. Thermal sweating was qualitatively assessed with a modified version of Minor's colorimetric methods. Thermoregulatory and acetylcholine-induced focal sweat rates were measured with capacitance hydrometers. RESULTS: Thermoregulatory sweating was almost normal without anhidrotic area in 29.8% of PD patients, slightly defective in 38.7%, with anhidrotic area across <1/4 of the body surface, moderately defective in 22.2% with anhidrotic area across approximately 1/2 of the body surface, and extremely defective in 9.3% with anhidrotic area across more than 3/4 of the body surface. Patchy sweating was observed in 104 patients, implicating involvement of the hypothalamo-spinal and/or preganglionic systems in the disease process. Hyperhidrosis was seen in 15% of patients. Tremor-dominant group showed least impairment. CONCLUSION: This study suggests that PD is associated with various patterns and degree of sudomotor abnormalities, and that sudomotor sympathetic deficits may be related with the pathophysiology of akinesia and rigidity rather than that of resting tremor.

Tako-Tsubo Syndrome in Amyotrophic Lateral Sclerosis: Single-Center Case Series and Brief Literature Review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with variable phenotypic expressions which has been associated with autonomic dysfunction. The cardiovascular system seems to be affected especially in the context of bulbar involvement. We describe four new cases of Tako-Tsubo syndrome (TTS) in ALS patients with an appraisal of the literature. We present a late-stage ALS patient with prominent bulbar involvement that presented TTS during hospitalization. We then retrospectively identify three additional ALS-TTS cases reporting relevant clinical findings. TTS cardiomyopathy has been observed in different acute neurological conditions, and the co-occurrence of ALS and TTS has already been reported. Cardiovascular autonomic dysfunctions have been described in ALS, especially in the context of an advanced diseases and with bulbar involvement. Noradrenergic hyperfunction linked to sympathetic denervation and ventilatory deficits coupled in different instances with a trigger event could play a synergistic role in the development of TTS in ALS. Sympathetic hyperfunctioning and ventilatory deficits in conjunction with cardiac autonomic nerves impairment may play a role in the development of TTS in a context of ALS.

Adynamic response to cold pain reflects dysautonomia in type 1 diabetes and polyneuropathy.

Cardiac autonomic neuropathy (CAN), widely assessed by heart rate variability (HRV), is a common complication of long-term diabetes. We hypothesized that HRV dynamics during tonic cold pain in individuals with type 1 diabetes mellitus (T1DM) could potentially demask CAN. Forty-eight individuals with long-term T1DM and distal symmetrical polyneuropathy and 21 healthy controls were included. HRV measures were retrieved from 24-h electrocardiograms. Moreover, ultra-short-term HRV recordings were used to assess the dynamic response to the immersion of the hand into 2 °C cold water for 120 s. Compared to healthy, the T1DM group had expectedly lower 24-h HRV measures for most components (p < 0.01), indicating dysautonomia. In the T1DM group, exposure to cold pain caused diminished sympathetic (p < 0.001) and adynamic parasympathetic (p < 0.01) HRV responses. Furthermore, compared to healthy, cold pain exposure caused lower parasympathetic (RMSSD: 4% vs. 20%; p = 0.002) and sympathetic responses (LF: 11% vs. 73%; p = 0.044) in the T1MD group. QRISK3-scores are negatively correlated with HRV measures in 24-h and ultra-short-term recordings. In T1DM, an attenuated sympathovagal response was shown as convincingly adynamic parasympathetic responses and diminished sympathetic adaptability, causing chronometric heart rhythm and rigid neurocardiac regulation threatening homeostasis. The findings associate with an increased risk of cardiovascular disease, emphasizing clinical relevance.

Reduced slow-wave activity and autonomic dysfunction during sleep precede cognitive deficits in Alzheimer's disease transgenic mice.

Occurrence of amyloid-ß (Aß) aggregation in brain begins before the clinical onset of Alzheimer's disease (AD), as preclinical AD. Studies have reported that sleep problems and autonomic dysfunction associate closely with AD. However, whether they, especially the interaction between sleep and autonomic function, play critical roles in preclinical AD are unclear. Therefore, we investigated how sleep patterns and autonomic regulation at different sleep-wake stages changed and whether they were related to cognitive performance in pathogenesis of AD mice. Polysomnographic recordings in freely-moving APP/PS1 and wild-type (WT) littermates were collected to study sleep patterns and autonomic function at 4 (early disease stage) and 8 months of age (advanced disease stage), cognitive tasks including novel object recognition and Morris water maze were performed, and Aß levels in brain were measured. APP/PS1 mice at early stage of AD pathology with Aß aggregation but without significant differences in cognitive performance had frequent sleep-wake transitions, lower sleep-related delta power percentage, lower overall autonomic activity, and lower parasympathetic activity mainly during sleep compared with WT mice. The same phenomenon was observed in advanced-stage APP/PS1 mice with significant cognitive deficits. In mice at both disease stages, sleep-related delta power percentage correlated positively with memory performance. At early stage, memory performance correlated positively with sympathetic activity during wakefulness; at advanced stage, memory performance correlated positively with parasympathetic activity during both wakefulness and sleep. In conclusion, sleep quality and distinction between wake- and sleep-related autonomic function may be biomarkers for early AD detection.