Interrelatedness of steering and lateral position parameters: Recommendations for the assessment of driving performance.

INTRODUCTION: Loss of attention leads to less steady driving within the lane and is one of the main causes of road accidents. To improve road safety, vehicle-based parameters such as steering wheel angle and lateral position are used to objectively assess driving performance, especially in monotonous driving tasks. METHOD: The present driving simulator study investigated the extent to which eight commonly used parameters are independent indicators of driving performance. Fifteen participants undertook a monotonous highway driving task for 1 h. Four steering angle parameters were examined: average steering angle (ASA), standard deviation of steering angle (SDSA), steering angle range (SAR), and steering reversal rate (SRR); as well as four lateral position parameters: mean lateral position (MLP), standard deviation of lateral position (SDLP), lateral position range (LPR), and the out-of-lane duration. Measurements were averaged across 2-minute epochs. Repeated measures correlation analysis evaluated the similarity between each parameter, and the variance inflation factor test evaluated the multicollinearity of all the parameters. RESULTS: The results demonstrated that some parameters are highly correlated and should not be used together to assess driving performance. It is recommended that the optimal combination is ASA and SAR to assess steering angle, and SDLP and out-of-lane to assess lateral position. Out-of-lane, as a factor directly contributing to road safety, is recommended because it has the least correlation with other parameters. PRACTICAL APPLICATIONS: If implemented, these recommendations may improve the assessment of driving performance in future studies.

The Catastrophe of Intracerebral Hemorrhage Drives the Capillary-Hemorrhage Dementias, Including Alzheimer's Disease.

This review advances an understanding of several dementias, based on four premises. One is that capillary hemorrhage is prominent in the pathogenesis of the dementias considered (dementia pugilistica, chronic traumatic encephalopathy, traumatic brain damage, Alzheimer's disease). The second premise is that hemorrhage introduces four neurotoxic factors into brain tissue: hypoxia of the tissue that has lost its blood supply, hemoglobin and its breakdown products, excitotoxic levels of glutamate, and opportunistic pathogens that can infect brain cells and induce a cytotoxic immune response. The third premise is that where organisms evolve molecules that are toxic to itself, like the neurotoxicity ascribed to hemoglobin, amyloid- (A), and glutamate, there must be some role for the molecule that gives the organism a selection advantage. The fourth is the known survival-advantage roles of hemoglobin (oxygen transport), of A (neurotrophic, synaptotrophic, detoxification of heme, protective against pathogens) and of glutamate (a major neurotransmitter). From these premises, we propose 1) that the brain has evolved a multi-factor response to intracerebral hemorrhage, which includes the expression of several protective molecules, including haptoglobin, hemopexin and A; and 2) that it is logical, given these premises, to posit that the four neurotoxic factors set out above, which are introduced into the brain by hemorrhage, drive the progression of the capillary-hemorrhage dementias. In this view, A expressed at the loci of neuronal death in these dementias functions not as a toxin but as a first responder, mitigating the toxicity of hemoglobin and the infection of the brain by opportunistic pathogens.

Is driving experience all that matters? Drivers' takeover performance in conditionally automated driving.

INTRODUCTION: In conditionally automated driving, drivers are allowed to engage in non-driving related tasks (NDRTs) and are occasionally requested to take over vehicle control in situations that the automation system cannot handle. Drivers may not be able to adequately perform such requests if they have limited driving experience. This study investigates the influence of driving experience on takeover performance in conditionally automated driving. METHOD: Nineteen subjects participated in this driving simulator study. The NDRTs consisted of three tasks: writing business emails (working condition), watching videos (entertaining condition), and taking a break with eyes closed (resting condition). These three NDRTs require drivers to invest high, moderate, and low levels of mental workload, respectively. The duration of engagement in each NDRT before a takeover request (TOR) was either 5 minutes (short interval) or 30 minutes (long interval). RESULTS: Drivers' driving experience and performance during the control period are highly correlated with their TOR performance. Furthermore, the type and duration of NDRT influence TOR performance, and inexperienced drivers exhibit poorer TOR performance than experienced drivers. CONCLUSIONS AND PRACTICAL APPLICATIONS: These findings have relevance for the types of NDRTs that ought to be permitted during automated driving, the design of automated driving systems, and the formulation of regulations regarding the responsible use of automated vehicles.

Twelve protections evolved for the brain, and their roles in extending its functional life.

As human longevity has increased, we have come to understand the ability of the brain to function into advanced age, but also its vulnerability with age, apparent in the age-related dementias. Against that background of success and vulnerability, this essay reviews how the brain is protected by (by our count) 12 mechanisms, including: the cranium, a bony helmet; the hydraulic support given by the cerebrospinal fluid; the strategically located carotid body and sinus, which provide input to reflexes that protect the brain from blood-gas imbalance and extremes of blood pressure; the blood brain barrier, an essential sealing of cerebral vessels; the secretion of molecules such as haemopexin and (we argue) the peptide Aß to detoxify haemoglobin, at sites of a bleed; autoregulation of the capillary bed, which stabilises metabolites in extracellular fluid; fuel storage in the brain, as glycogen; oxygen storage, in the haemoprotein neuroglobin; the generation of new neurones, in the adult, to replace cells lost; acquired resilience, the stress-induced strengthening of cell membranes and energy production found in all body tissues; and cognitive reserve, the ability of the brain to maintain function despite damage. Of these 12 protections, we identify 5 as unique to the brain, 3 as protections shared with all body tissues, and another 4 as protections shared with other tissues but specialised for the brain. These protections are a measure of the brain's vulnerability, of its need for protection. They have evolved, we argue, to maintain cognitive function, the ability of the brain to function despite damage that accumulates during life. Several can be tools in the hands of the individual, and of the medical health professional, for the lifelong care of our brains.

Associations Between Amyloid Burden, Hypoxemia, Sleep Architecture, and Cognition in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-ß (Aß) burden, the hallmark of Alzheimer's disease, and cognitive decline. OBJECTIVE: To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA. METHODS: Thirty-four individuals with confirmed OSA (mean±SD age 57.5±4.1 years; 19 males) and 12 healthy controls (58.5±4.2 years; 6 males) underwent a clinical polysomnogram, a NAV4694 positron emission tomography (PET) scan for Aß burden, assessment of APOEɛ status and cognitive assessments. Linear hierarchical regressions were conducted to determine the contributions of demographic and sleep variables on amyloid burden and cognition. RESULTS: Aß burden was associated with nocturnal hypoxemia, and impaired verbal episodic memory, autobiographical memory and set shifting. Hypoxemia was correlated with impaired autobiographical memory, and only set shifting performance remained significantly associated with Aß burden when controlling for sleep variables. CONCLUSIONS: Nocturnal hypoxemia was related to brain Aß burden in this sample of OSA participants. Aß burden and hypoxemia had differential impacts on cognition. This study reveals aspects of sleep disturbance in OSA that are most strongly associated with brain Aß burden and poor cognition, which are markers of early Alzheimer's disease. These findings add weight to the possibility that hypoxemia may be causally related to the development of dementia; however, whether it may be a therapeutic target for dementia prevention in OSA is yet to be determined.

Effects of whole-body vibration on driver drowsiness: A review.

INTRODUCTION: Whole-body vibration has direct impacts on driver vigilance by increasing physical and cognitive stress on the driver, which leads to drowsiness, fatigue and road traffic accidents. Although sleep deprivation, sleep apnoea and alcohol consumption can also lead to driver drowsiness, exposure to steady vibration is the factor most readily controlled by changes to vehicle design, yet it has received comparatively less attention. METHODS: This review investigated interrelationships between the various components of whole-body vibration and the physiological and cognitive parameters that lead to driver drowsiness, as well as the effects of vibration parameters (frequency, amplitude, waveform and duration). Vibrations transmitted to the driver body from the vehicle floor and/or seat have been considered for this review, whereas hand-arm vibration, shocks, acute or transient vibration were excluded from consideration. RESULTS: Drowsiness is affected by interactions between the frequency, amplitude, waveform and duration of the vibration. Under optimal conditions, whole-body vibration can induce significant drowsiness within 30 min. Low frequency whole-body vibrations, particularly vibrations of 4-10 Hz, are most effective at inducing drowsiness. This review notes some limitations of current studies and suggests directions for future research. CONCLUSIONS: This review demonstrated a strong causal link exists between whole-body vibration and driver drowsiness. Since driver drowsiness has been established to be a significant contributor to motor vehicle accidents, research is needed to identify ways to minimise the components of whole-body vibration that contribute to drowsiness, as well as devising more effective ways to counteract drowsiness. PRACTICAL APPLICATIONS: By raising awareness of the vibrational factors that contribute to drowsiness, manufacturers will be prompted to design vehicles that reduce the influence of these factors.

Association between cognitive dysfunction and nocturnal peaks of blood pressure estimated from pulse transit time in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by recurrent episodes of partial or complete cessation of breathing during sleep and an increased effort to breathe. Patients with untreated OSA exhibit cognitive impairment that is only partly accounted for by hypoxia and sleep disruption, suggesting that other factors remain to be identified. OSA can involve repeated spikes of nocturnal blood pressure because of increased activity of the sympathetic nervous system during sleep. While high resting blood pressure is associated with cognitive dysfunction, it is not yet known whether peaks in nocturnal blood pressure are associated with cognitive impairment in OSA. METHODS: A cohort of patients participated in overnight polysomnographic studies at a major sleep laboratory to investigate whether nocturnal elevations in blood pressure are associated with cognitive dysfunction in OSA. Nocturnal pulse transit time was measured as a surrogate for arterial blood pressure during sleep. RESULTS: Of the 75 patients, 12 had no obstructive sleep apnoea, 26 had mild OSA, 18 moderate, and 19 severe OSA. The results revealed that systolic blood pressure peaks were associated with OSA severity, while diastolic blood pressure peaks were not. Peaks of nocturnal systolic blood pressure were independently associated with poorer performance on a test of visuospatial function, but not with impairments on tests of sustained attention, reaction time or autobiographical memory. CONCLUSION: The present findings indicate nocturnal peaks of systolic blood pressure that are substantially higher than normal daytime values may contribute to visuospatial dysfunction in OSA.

Quantitative analysis of size and regional distribution of corpora amylacea in the hippocampal formation of obstructive sleep apnoea patients.

Corpora amylacea (CoA) are spherical aggregates of glucose polymers and proteins within the periventricular, perivascular and subpial regions of the cerebral cortex and the hippocampal cornu ammonis (CA) subfields. The present study quantified the distribution of CoA in autopsied hippocampi of patients with obstructive sleep apnoea (OSA) using ethanolamine-induced fluorescence. CoA were observed in 29 of 30 patients (96.7%). They were most abundant in periventricular regions (wall of lateral ventricle, alveus, fimbria and CA4), rarely found in the CA3 and CA1, and undetectable in the CA2 or subiculum. A spatiotemporal sequence of CoA deposition was postulated, beginning in the fimbria and progressively spreading around the subpial layer until they extended medially to the wall of the lateral ventricle and laterally to the collateral sulcus. This ranked CoA sequence was positively correlated with CoA packing density (count and area fraction) and negatively correlated with CoA minimum diameters (p < 0.05). Although this sequence was not correlated with age or body mass index (BMI), age was positively correlated with the mean and maximum diameters of CoA. These findings support the view that the spatiotemporal sequence of CoA deposition is independent of age, and that CoA become larger due to the accretion of new material over time.

Association between nocturnal activity of the sympathetic nervous system and cognitive dysfunction in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with repetitive breathing obstructions during sleep. These episodes of hypoxia and associated arousals from sleep induce physiological stress and nocturnal over-activation of the sympathetic nervous system (SNS). One consequence of OSA is impairment in a range of cognitive domains. Previous research into cognitive impairment in OSA have focussed on intermittent hypoxia and disrupted sleep, but not nocturnal over-activation of the SNS. Therefore, we investigated whether nocturnal over-activity of the SNS was associated with cognitive impairments in OSA. The extent of nocturnal SNS activation was estimated from heart rate variability (HRV), pulse wave amplitude (PWA) and stress response biomarkers (cortisol and glucose levels). OSA severity was significantly associated with PWA indices and the HRV low frequency/ high frequency ratio (p < 0.05). Morning blood glucose levels were significantly associated with the duration of a blood oxygen saturation (SaO2) < 90% (p < 0.01). PWA and HRV were significantly associated with the time taken to perform a task involving visuospatial functioning (p < 0.05), but not with impairments in sustained attention, reaction time or autobiographical memory. These results suggest that the visuospatial dysfunction observed in people with OSA is associated with increased nocturnal activity of the SNS.

Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea.

Obstructive sleep apnea (OSA) involves intermittent cessations of breathing during sleep. People with OSA can experience memory deficits and have reduced hippocampal volume; these features are also characteristic of Alzheimer's disease (AD), where they are accompanied by neurofibrillary tangles (NFTs) and amyloid beta (Aß) plaques in the hippocampus and brainstem. We have recently shown reduced hippocampal volume to be related to OSA severity, and although OSA may be a risk factor for AD, the hippocampus and brainstems of clinically verified OSA cases have not yet been examined for NFTs and Aß plaques. The present study used quantitative immunohistochemistry to investigate postmortem hippocampi of 34 people with OSA (18 females, 16 males; mean age 67 years) and brainstems of 24 people with OSA for the presence of NFTs and Aß plaques. OSA severity was a significant predictor of Aß plaque burden in the hippocampus after controlling for age, sex, body mass index (BMI), and continuous positive airway pressure (CPAP) use. OSA severity also predicted NFT burden in the hippocampus, but not after controlling for age. Although 71% of brainstems contained NFTs and 21% contained Aß plaques, their burdens were not correlated with OSA severity. These results indicate that OSA accounts for some of the "cognitively normal" individuals who have been found to have substantial Aß burdens, and are currently considered to be at a prodromal stage of AD.

Differential associations of hypoxia, sleep fragmentation, and depressive symptoms with cognitive dysfunction in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete cessation of breathing during sleep and increased effort to breathe. This study examined patients who underwent overnight polysomnographic studies in a major sleep laboratory in Saudi Arabia. The study aimed to determine the extent to which intermittent hypoxia, sleep disruption, and depressive symptoms are independently associated with cognitive impairments in OSA. In the sample of 90 participants, 14 had no OSA, 30 mild OSA, 23 moderate OSA, and 23 severe OSA. The findings revealed that hypoxia and sleep fragmentation are independently associated with impairments of sustained attention and reaction time (RT). Sleep fragmentation, but not hypoxia, was independently associated with impairments in visuospatial deficits. Depressive symptoms were independently associated with impairments in the domains of sustained attention, RT, visuospatial ability, and semantic and episodic autobiographical memories. Since the depressive symptoms are independent of hypoxia and sleep fragmentation, effective reversal of cognitive impairment in OSA may require treatment interventions that target each of these factors.

Severe Obstructive Sleep Apnea Is Associated with Higher Brain Amyloid Burden: A Preliminary PET Imaging Study.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to an increase risk of dementia. Few studies have cross-sectionally examined whether clinically-confirmed OSA is associated with a higher brain amyloid burden. OBJECTIVE: The aim of this study was to compare brain amyloid burden in individuals with untreated OSA and healthy controls, and explore associations between amyloid burden and polysomnographic and subjective measures of sleep, demographics, and mood. METHODS: Thirty-four individuals with OSA (mean age 57.5±4.1 y; 19 males) and 12 controls (mean age 58.5±4.2 y; 6 males) underwent a clinical polysomnogram and a 11C-PiB positron emission tomography (PET) scan to quantify amyloid burden. RESULTS: Amyloid burden was elevated in the OSA group relative to controls, and was significantly higher in those with severe OSA relative to mild/moderate OSA. Correlation analyses indicated that higher amyloid burden was associated with a higher Non-REM apnea hypopnea index, poorer sleep efficiency, and less time spent in stage N3 sleep, when controlling for age. CONCLUSION: Severe OSA is associated with a modest elevation of brain amyloid, the significance of which should be further investigated to explore the implications for dementia risk.

Measurement of hand grip strength in the elderly: A scoping review with recommendations.

INTRODUCTION: Hand grip strength has been widely used as a lead measure in geriatric conditions such as frailty. However, diversity in assessment protocols and methodologies creates uncertainty in the comparison of outcome measurements. The aim of this study was to review the literature relating to the measurement of hand grip strength in older adults, in order to develop further consensus in relation to the use of existing protocols in clinical and community settings, with an emphasis on practicality and suitability for frail persons. METHODS: Five electronic English databases were searched using keywords such as 'hand grip strength', 'clinimetric assessment', and their synonyms. Age-related trends in adults aged ≥65 years were assessed, and comparisons were made of the following variables: dynamometer model and handle setting, hand positioning, warm-up trials, grip duration, number of repeated tests, rest periods, laterality of tested hand, and whether encouragement was given to the subjects. RESULTS: Thirty-four research papers met the inclusion criteria and were included. A Jamar hand dynamometer was most frequently used. Variations were found in the positioning of the subject and in the duration of the rest period, which ranged from 10 to 20 s to 1 min. Grip strength was typically measured three times in the dominant hand, with the strongest grip being recorded and no encouragement being provided during assessment. CONCLUSIONS: Based on the scoping review, we propose a detailed and standardised protocol that is suitable for the assessment of hand grip strength in frail older adults.

Assessment of Gait Speed in Older Adults.

BACKGROUND AND PURPOSE: Gait speed is an important measure of functional ability and has been widely used in older adults as an indicator of frailty. However, the diversity in measurement protocols in clinical settings creates variability in outcome measures. The aim of this study was to systematically review the literature relating to the measurement of gait speed in older adults, to propose a protocol suitable for use in clinical and community settings. METHODS: A total of 5 electronic English databases were searched (PubMed, EMBASE, AMED, CINAHL, and SPORTDiscus) using key words and synonyms related to gait speed. RESULTS: Fifty relevant articles were identified, with variability being found between studies in the essential elements (timing device, walking distance, timing points, use of walking aids, pace of performance, and total tests recorded) of gait measurement. The majority of studies used unspecified timing devices while others used electronic gait mats or infrared beams linked to electronic stopwatches. Walking distance was assessed over distances between 2.4 and 15 m, with 4 m most commonly used. Most studies permitted the use of walking aids, with assessments being repeated at a usual pace, and the maximum value recorded in meters per second. CONCLUSION: A standardized measurement protocol is proposed for measuring gait speed in older adults.

What is the optimal chair stand test protocol for older adults? A systematic review.

Purpose: To determine the chair stand test protocol that is most suitable for older adults in clinical settings by reviewing the currently available methods.Methods: Five electronic English databases were searched and details of methods used on individuals aged ≥65 years in the included studies were compared, including the instrument used to record time, units of measurement, chair characteristics (seat height, armrests), footwear, permission to use upper extremities and walking aids, pace of performance, total number of chair stands, timing points, total number of recorded and practice tests.Results: A total of 23 eligible studies were identified. The type of instrument to record performance time, characteristics of the chair and footwear were not frequently mentioned. A majority of studies did not permit the use of the upper extremities or walking aids during assessment. The performance of five chair stands at a fast pace recorded in seconds was most common, with the majority of studies recording the initial and end time point in a seated position. The total number of performed tests and practice tests was not specified in a majority of studies.Conclusion: A feasible and safe protocol for the chair stand test is proposed for assessment of older adults.Implications for RehabilitationThe chair stand test may provide valuable information on declines in mobility in older adults.The use of the chair stand test within clinical settings of older adults may provide a measure to identify frail individuals and to determine their level of frailty.Using the proposed protocol for the chair stand test may allow for the comparability of results.

Matrine Protects Against MCD-Induced Development of NASH via Upregulating HSP72 and Downregulating mTOR in a Manner Distinctive From Metformin.

The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NASH with or without the treatment of matrine (100 mg/kg/day in diet). Metformin was used (250 mg/kg/day in diet) as a comparator for mechanistic investigation. Administration of matrine significantly reduced MCD-induced elevations in plasma ALT and AST but without changing body or liver fat content. Along with alleviating liver injury, matrine suppressed MCD-induced hepatic inflammation (indicated by TNFα, CD68, MCP-1, and NLRP3) and fibrosis (indicated by collagen 1, TGFß, Smad3, and sirius-red staining). In comparison, metformin treatment did not show any clear sign of effects on these parameters indicative of NASH. Further examination of the liver showed that matrine treatment rescued the suppressed HSP72 (a chaperon protein against cytotoxicity) and blocked the induction of mTOR (a key protein in a stress pathway). In keeping with the lack of the improvement of the NASH features, metformin did not show any significant effect against MCD-induced changes in HSP72 and mTOR. Matrine protects against MCD-induced development of NASH which is refractory to metformin treatment. Its anti-NASH effects involve enhancing HSP72 and downregulating mTOR but do not rely on amelioration of hepatosteatosis.

Autobiographical Memory From Different Life Stages in Individuals With Obstructive Sleep Apnea.

OBJECTIVES: Autobiographical memory dysfunction is a marker of vulnerability to depression. Patients with obstructive sleep apnea (OSA) experience high rates of depression and memory impairment, and autobiographical memory impairments have been observed compared to healthy controls; however, these groups were not age-matched. This study aimed to determine whether individuals with untreated OSA have impaired autobiographical memory when compared to age-matched controls, and to assess the quality of autobiographical memories from three broad time points. METHODS: A total of 44 participants with OSA (M age=49.4±13.0) and 44 age-matched controls (M age=50.0±13.1) completed the Autobiographical Memory Interview (AMI) to assess semantic and episodic memories from three different life stages, and 44 OSA participants and 37 controls completed the Autobiographical Memory Test (AMT) to assess overgeneral memory recall (an inability to retrieve specific memories). RESULTS: OSA participants had significantly poorer semantic recall of early adult life on the AMI (p<.001), and more overgeneral autobiographical memories recalled on the AMT (=.001), than controls. Poor semantic recall from early adult life was significantly correlated with more depressive symptoms (p=0.006) and lower education (p<0.02), while higher overgeneral memory recall was significantly associated with older age (p=.001). CONCLUSIONS: A specific deficit in semantic autobiographical recall was observed in individuals with OSA. OSA patients recalled more overgeneral memories, suggesting that aspects of the sleep disorder affect their ability to recollect specific details of events from their life. These cognitive features of OSA may contribute to the high incidence of depression in this population. (JINS 2019, 25, 266-274).

Neuropathological investigation of cell layer thickness and myelination in the hippocampus of people with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is commonly associated with memory impairments. Although MRI studies have found volumetric differences in the hippocampus of people with OSA compared with controls, MRI lacks the spatial resolution to detect changes in the specific regions of the hippocampus that process different types of memory. The present study performed histopathological investigations on autopsy brain tissue from 32 people with OSA (17 females and 15 males) to examine whether the thickness and myelination of the hippocampus and entorhinal cortex (EC) vary as a function of OSA severity. Increasing OSA severity was found to be related to cortical thinning in the molecular layer of the dentate gyrus (r2 = 0.136, p = 0.038), the CA1 (overall, r2 = 0.135, p = 0.039; layer 1, r2 = 0.157, p = 0.025; layer 2, r2 = 0.255, p = 0.003; and layer 3, r2 = 0.185, p = 0.014) and in some layers of the EC (layer 1, r2 = 0.186, p = 0.028; trend in layer 3, r2 = 0.124, p = 0.078). OSA severity was also related to decreased myelin in the deep layers but not the superficial layers of the EC (layer 6, r2 = 0.282, p = 0.006; deep white matter, r2 = 0.390, p = 0.001). Patients known to have used continuous positive airway pressure (CPAP) treatment showed no significant reductions in cortical thickness when compared with controls, suggesting that CPAP had a protective effect. However, CPAP did not protect against myelin loss. The regions of decreased cortical thickness and demyelination are locations of synaptic connections in both the polysynaptic (episodic and spatial) and direct (semantic) memory pathways and may underpin the impairments observed in episodic, semantic, and spatial memory in people with OSA.

The Physiological Roles of Amyloid-ß Peptide Hint at New Ways to Treat Alzheimer's Disease.

Amyloid-ß (Aß) is best known as the misfolded peptide that is involved in the pathogenesis of Alzheimer's disease (AD), and it is currently the primary therapeutic target in attempts to arrest the course of this disease. This notoriety has overshadowed evidence that Aß serves several important physiological functions. Aß is present throughout the lifespan, it has been found in all vertebrates examined thus far, and its molecular sequence shows a high degree of conservation. These features are typical of a factor that contributes significantly to biological fitness, and this suggestion has been supported by evidence of functions that are beneficial for the brain. The putative roles of Aß include protecting the body from infections, repairing leaks in the blood-brain barrier, promoting recovery from injury, and regulating synaptic function. Evidence for these beneficial roles comes from in vitro and in vivo studies, which have shown that the cellular production of Aß rapidly increases in response to a physiological challenge and often diminishes upon recovery. These roles are further supported by the adverse outcomes of clinical trials that have attempted to deplete Aß in order to treat AD. We suggest that anti-Aß therapies will produce fewer adverse effects if the known triggers of Aß deposition (e.g., pathogens, hypertension, and diabetes) are addressed first.