Cerebrospinal fluid (CSF) orexin levels are higher in MCI and AD and associated with sleep deterioration, increasing risk of cognitive decline and Alzheimer's disease (AD) progression. Orexin-A is a key sleep-wake cycle regulator. Dual orexin receptor antagonists improve sleep in AD and insomnia and may reduce tau and Aβ deposition in older adults. However, little research has investigated associations between sleep microarchitecture, orexin, neurodegeneration biomarkers, cognitive decline, or mental health in AD. Using data from a prospective cohort study of mild-to-moderate AD ( n  = 60, 30-female, mean age-74.7), we analysed non-REM sleep spindles, slow oscillations (SO), and their associations with CSF orexin, AD biomarkers, cognition, and mental health over three years. Participants underwent polysomnography (PSG) and CSF draws at baseline, neuropsychological assessment with the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) at baseline and 12 months, and Mini-Mental Status Examination (MMSE) at baseline, 12, 24, and 36 months. PSG was scored along American Academy of Sleep Medicine guidelines. Spindle and SO detection were performed using in-house, open-source software packages developed at Concordia University, following Moelle (2011) recommendations for spindles and Staresina's (2015) recommendations for SO. Associations between SO and spindle characteristics (duration, density, power, amplitude) and orexin, Aβ42 and tau at baseline, and baseline orexin and cognition from baseline to 36 months were investigated with false discovery rate-adjusted generalised linear models, controlling for age, sex, apnea-hypopnea index. We found previously unreported, predictive associations between SO, duration, density, amplitude, and CSF orexin. Orexin also predicted increased ptau181, total-tau, ptau/Aβ42, total-tau/Aβ42. Increased orexin predicted worse cognitive performance (higher ADAS-cog, lower MMSE) from baseline to 36-months and increased neuropsychiatric symptom severity (NPI) from baseline to 12 months. Orexin also moderates relationships between spindles, SO, cognition, and mental health. Orexin levels are associated with neurodegeneration biomarkers and cognitive deterioration in AD and moderate relationships between sleep microarchitecture and cognitive changes over time. Orexin may thus constitute a potential target for sleep-related interventions for cognition in neurodegenerative disorders.

Sleep is essential for brain-health, including clearance of β-amyloid (Aβ), tau, and otherpromising diagnostic markers of neurodegeneration and progression in Alzheimer's Disease (AD): cerebrospinal fluid neurofilament-light chain (NfL), neurogranin-36 (NG-36), and Chitinase-3-like protein-1 (YKL-40). However, it remains unclear which sleep characteristics predict these biomarkers or whether the biomarkers predict cognitive or neuropsychiatric decline after AD onset. Using data from a prospective cohort study of mild-to-moderate AD ( n  = 60, 30-female, mean age 74.7), we analysed non-rapid eye-movement sleep spindles and slow oscillations (SO) at baseline and their associations with baseline NfL, YKl-40, NG-36, NfL/Aβ42, YKl-40/Aβ42, and whether these biomarkers predict cognition and mental health from baseline to three-years follow-up. Participants underwent baseline polysomnography (PSG) and cerebrospinal fluid draws for amyloid and tau, and neuropsychological assessment at baseline, 12, 24 and 36 months with the Mini-Mental Status Examination (MMSE), and the Alzheimer's Disease AssessmentScale-Cognitive Subscale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) at baseline and 12 months. Spindle and SO detection were performed using in-house, open-source software packages developed at Concordia University. Associations between SO and spindle characteristics (duration, density, power, amplitude), biomarkers, and cognition from baseline to 36 months were investigated with false discovery rate-adjusted robust regression controlling for age, sex, apnea-hypopnea index. We found previously unreported associations between spindle and SO characteristics, NfL, YKl-40, NG-36, NfL/Aβ42 (β=-.0029, p  = 0.001), YKl-40/Aβ42 (β=0.0004, p  = 0.003) and cognition in persons with AD. These biomarkers predicted worse cognitive performance (higher ADAS-cog [β=2.28, p  = 0.004], lower MMSE scores [β= -2.42, p  = 0.01]) from baseline to 36-months, and a significant increase in neuropsychiatric symptom severity (NPI β=16.93 p  <0.001). NfL/Aβ42 mediated the effects of spindle activity on cognitive performance on the ADAS-cog ( p  =  0.041) and MMSE ( p  = 0.0019). Biomarkers also moderated the relationships between spindle and SO activity on cognition, and spindles and SO moderated the relationships between these biomarkers and cognition. Our novel findings demonstrate that spindle and SO activity are associated with NfL, YKl-40, and NG-36, and cognitive decline, constituting predictive, non-invasive biomarkers of neurodegeneration, cognition, and mental health in AD. They may thus provide novel treatment targets for delaying AD progression.

Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer’s disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood from AD patients with severe OSA compared with those with nonsevere OSA. We included 40 AD patients diagnosed based on clinical manifestations and AD biomarker levels in cerebrospinal fluid (CSF). Severe or nonsevere OSA (apnoea–hypoapnoea index ³ 30/h and < 30/h, respectively) was diagnosed through overnight polysomnography (PSG). The expression levels of 136 inflammation-related and 84 redox-related genes were evaluated by whole blood targeted transcriptomics. We identified three inflammatory genes and six redox genes that were upregulated in AD patients with severe OSA. Of all upregulated genes, TNFSF14 and ALOX12 (inflammatory and redox genes, respectively) were positively correlated with the arousal index. GSR, a redox gene, was positively correlated with the AHI (p<0.05). Finally, we found good correlations between the three inflammatory genes and six redox genes (p<0.05). A pathway enrichment analysis showed a strong enrichment of the serotonergic synapse pathway in severe OSA AD patients. Our results show an upregulation of nine genes involved in NF-κB-mediated inflammation and redox metabolism in the blood of patients with mild AD with severe OSA. Therefore, OSA may worsen the inflammation and oxidative damage that are already altered in patients with AD.

INTRODUCTION:Changes in sleep physiology can predate cognitive symptoms by decades in persons with Alzheimer's disease (AD), but it remains unclear which sleep characteristics predict cognitive and neurodegenerative changes after AD onset. METHODS:Using data from a prospective cohort of mild to moderate AD (n = 60), we analyzed non-rapid eye movement sleep spindles and slow oscillations (SOs) at baseline and their associations with baseline amyloid beta (Aβ) and tau and with cognition from baseline to 3-year follow-up. RESULTS:Higher spindle and SO activity predicted significant changes in Aβ and tau at baseline, lower Alzheimer's Disease Assessment Scale Cognitive Subscale (better cognitive performance) score, and higher Mini-Mental State Examination score from baseline to 36 months. Spindles and SOs mediated the effect of phosphorylated tau 181 (pTau181)/Aβ42 on cognition, while pTau181/aβ42 moderated the effect of spindles and SOs on cognition. DISCUSSION:Our findings demonstrate that spindle and SO activity during sleep constitute predictive and non-invasive biomarkers of neurodegeneration and cognition in AD patients. HIGHLIGHTS:Sleep spindles predict long-term cognitive performance in AD. Sleep spindle and SOs can be predictive, non-invasive biomarkers for AD. Sleep may be one of the most important modifiable risk factors for AD progression. Sleep microarchitecture is a novel therapeutic target for preserving brain heath. Sleep physiology can provide novel therapeutic targets to slow AD progression.

In the present study we aimed to assess the cognition of post-COVID condition (PCC) participants regarding their sleep quality, and to analyse different possible moderators of this effect, such as quality of life (European Quality of Life-5 Dimensions, EQ-5D), fatigue (Chadler Fatigue Questionnaire, CFQ), cognitive reserve (Cognitive Reserve Questionnaire, CRC), and subjective cognitive complaints (Memory Failures of Everyday Questionnaire, MFE-30). We included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) that were assessed with a comprehensive neuropsychological battery and different questionnaires. We included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) that were assessed with a comprehensive neuropsychological battery and different questionnaires. We found that PCC participants with poor sleep quality have a 4.3% greater risk of having immediate verbal memory deficits the greater the MFE-30 score (Odd Ratio (OR) 1,043; Confidence Interval (CI) 1,023-1,063). Also, they multiply their risk of having immediate verbal memory disorders by 2.4 when the EQ-5D is low (OR 0,33; CI 0,145-0,748), and they have less risk of having delayed visual memory deficits the greater the CRC (OR 0,963; CI 0,929-0,999). With processing speed performance, PCC participants and poor sleep quality have a 6.7% greater risk of having deficits the greater the MFE (OR 1,059; CI 1,024-1,096) and the risk of slowing processing speed triples the lower the EQ-5D (OR 0,021; CI 0,003-0,141). These results indicate that poor subjective sleep quality plays a role as a potential trigger for cognitive deficits. Therapeutic strategies to maximize sleep quality would be reducing not only sleep disturbances, but perhaps also cognitive impairment in PCC participants.

BACKGROUND:Alzheimer's disease (AD) is the most common neurodegenerative dementia. Recent advancements in plasma biomarkers measuring phosphorylated tau (pTau), particularly pTau217, offer non-invasive, cost-effective alternatives to cerebrospinal fluid (CSF) and PET biomarkers for diagnosing AD. Plasma neurofilament light chain (NF-L) has also emerged as a potential marker of neurodegeneration. This multicenter study evaluated the utility of these biomarkers as diagnostic tools and explored their potential to facilitate implementation across multiple centers, ensuring diagnostic uniformity. METHOD:Patients with mild cognitive impairment or mild dementia were recruited in a multicenter study (seven hospitals in Catalonia). Plasma levels of pTau217 and NF-L were measured using Lumipulse G (Fujirebio). Their diagnostic accuracy was compared to established CSF biomarkers. Additionally, the influence of demographic factors such as age, sex, BMI, and glomerular filtration rate (GFR) on pTau217 levels was analyzed. RESULT:Of 212 enrolled patients, 27 were excluded due to pre-analytical complications. Therefore, 185 patients were analyzed [Table 1], including 50 non-neurodegenerative cases (SND), 119 AD cases, 5 Lewy body dementia cases (3 LBD Aβ-, 2 LBD Aβ+), and 12 frontotemporal dementia cases (9 FTD Aβ-, 3 FTD Aβ+). Plasma pTau217 detected amyloid pathology (Aβ+) with high accuracy using two cut-offs: a cut-off below 0.201 pg/mL yielded a sensitivity of 95%, with a negative predictive value of 87%. For values above 0.397 pg/mL, specificity reached 95%, with a positive predictive value of 97% [Figure 1]. These thresholds predicted β-amyloid status in 74% of cases. NF-L levels were elevated in neurodegenerative conditions with significant differences, but with low diagnostic precision (mean values: 26.434 vs 19.933 pg/mL, p = 0.01, AUC=0.634) [Figure 2]. Demographic factors, particularly BMI and GFR, had minimal effects on plasma biomarker levels, with limited impact on diagnostic performance. CONCLUSION:Plasma pTau217 showed high AD diagnostic accuracy, and may reduce the need for other procedures like CSF/PET. The use of two diagnostic thresholds appears optimal, with 26% of subjects in intermediate ranges, potentially indicating early AD changes. NF-L were elevated in neurodegeneration but showed limited clinical utility in our study. This study supports the use of pTau217 in clinical practice, promoting diagnostic uniformity across Catalonia.

Alzheimer's disease (AD) is the most common neurodegenerative dementia. Recent advancements in plasma biomarkers measuring phosphorylated tau (pTau), particularly pTau217, offer non-invasive, cost-effective alternatives to cerebrospinal fluid (CSF) and PET biomarkers for diagnosing AD. Plasma neurofilament light chain (NF-L) has also emerged as a potential marker of neurodegeneration. This multicenter study evaluated the utility of these biomarkers as diagnostic tools and explored their potential to facilitate implementation across multiple centers, ensuring diagnostic uniformity. Patients with mild cognitive impairment or mild dementia were recruited in a multicenter study (seven hospitals in Catalonia). Plasma levels of pTau217 and NF-L were measured using Lumipulse G (Fujirebio). Their diagnostic accuracy was compared to established CSF biomarkers. Additionally, the influence of demographic factors such as age, sex, BMI, and glomerular filtration rate (GFR) on pTau217 levels was analyzed. Of 212 enrolled patients, 27 were excluded due to pre-analytical complications. Therefore, 185 patients were analyzed [Table 1], including 50 non-neurodegenerative cases (SND), 119 AD cases, 5 Lewy body dementia cases (3 LBD Aβ-, 2 LBD Aβ+), and 12 frontotemporal dementia cases (9 FTD Aβ-, 3 FTD Aβ+). Plasma pTau217 detected amyloid pathology (Aβ+) with high accuracy using two cut-offs: a cut-off below 0.201 pg/mL yielded a sensitivity of 95%, with a negative predictive value of 87%. For values above 0.397 pg/mL, specificity reached 95%, with a positive predictive value of 97% [Figure 1]. These thresholds predicted β-amyloid status in 74% of cases. NF-L levels were elevated in neurodegenerative conditions with significant differences, but with low diagnostic precision (mean values: 26.434 vs 19.933 pg/mL, p  = 0.01, AUC=0.634) [Figure 2]. Demographic factors, particularly BMI and GFR, had minimal effects on plasma biomarker levels, with limited impact on diagnostic performance. Plasma pTau217 showed high AD diagnostic accuracy, and may reduce the need for other procedures like CSF/PET. The use of two diagnostic thresholds appears optimal, with 26% of subjects in intermediate ranges, potentially indicating early AD changes. NF-L were elevated in neurodegeneration but showed limited clinical utility in our study. This study supports the use of pTau217 in clinical practice, promoting diagnostic uniformity across Catalonia.

Genetic, metabolic, and clinical evidence links lipid dysregulation to an increased risk of Alzheimer’s disease (AD). However, the role of lipids in the pathophysiological processes of AD and its clinical progression is unclear. We investigated the association between cerebrospinal fluid (CSF) lipidome and the pathological hallmarks of AD, progression from mild cognitive impairment (MCI) to AD, and the rate of cognitive decline in MCI patients. The CSF lipidome was analyzed by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform for 209 participants: 91 AD, 92 MCI, and 26 control participants. The MCI patients were followed up for a median of 58 (± 12.5) months to evaluate their clinical progression to AD. Forty-eight (52.2%) MCI patients progressed to AD during follow-up. We found that higher CSF levels of hexacosanoic acid and ceramide Cer(d38:4) were associated with an increased risk of amyloid beta 42 (Aβ42) positivity in CSF, while levels of phosphatidylethanolamine PE(40:0) were associated with a reduced risk. Higher CSF levels of sphingomyelin SM(30:1) were positively associated with pathological levels of phosphorylated tau in CSF. Cholesteryl ester CE(11D3:1) and an unknown lipid were recognized as the most associated lipid species with MCI to AD progression. Furthermore, TG(O-52:2) was identified as the lipid most strongly associated with the rate of progression. Our results indicate the involvement of membrane and intracellular neutral lipids in the pathophysiological processes of AD and the progression from MCI to AD dementia. Therefore, CSF neutral lipids can be used as potential prognostic markers for AD.

Abstract Background Genetic, metabolic, and clinical evidence links lipid dysregulation to an increased risk of Alzheimer’s disease (AD). However, the role of lipids in the pathophysiological processes of AD and its clinical progression is unclear. Our objectives were to investigate the association between cerebrospinal fluid (CSF) lipidome and the pathological hallmarks of AD, progression from mild cognitive impairment (MCI) to AD, and the rate of cognitive decline in MCI patients.Methods We analysed the CSF lipidome by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform for 209 participants recruited consecutively: 91 AD, 92 MCI, and 26 control participants. Additional characteristic of the study population such as demographic data (age and sex), education, comorbidities, complete blood count, CSF AD biomarkers, MMSE scores and APOE ɛ4 allele were also collected.Results Forty-eight (52.2%) MCI patients progressed to AD during follow-up (58 ± 12.5 months). We found that higher CSF levels of hexacosanoic acid and ceramide Cer(d38:4) were associated with an increased risk of amyloid beta 42 (Aβ42) positivity in CSF, while levels of phosphatidylethanolamine PE(40:0) were associated with a reduced risk. Higher CSF levels of sphingomyelin SM(30:1) were positively associated with pathological levels of phosphorylated tau in CSF. Regarding the progression from MCI to AD, cholesteryl ester CE(11D3:1) and an unknown lipid were recognized as the most associated lipid species. Furthermore, TG(O-52:2) was identified as the lipid most strongly associated with the rate of progression.Conclusion Our results indicate the involvement of membrane and intracellular neutral lipids in the pathophysiological processes of AD and the progression from MCI to AD dementia. These data also suggest that lipid droplets may be involved, as a cause or consequence, in pathophysiological processes underlying neurodegeneration.

Diagnostic research criteria for Alzheimer’s Disease (AD) recommend the cerebrospinal fluid (CSF) as a sensible and validated biomarker to improve the accuracy of the prognosis regarding progression to dementia for people with mild cognitive impairment (MCI). Also, it has been established that episodic memory failure is a proxy for AD, while executive functions impairment could be leading to other types of dementia. One of the tests designed to simultaneously evaluate these cognitive functions with high sensitivity and specificity to discriminate between neurocognitive disorders is the Test of Memory Strategies (TMS). The main goals of the present study were 1) to assess the correlations between TMS and CSF markers (i.e., Aβ42, t-tau, and p-tau) in a sample of MCI patients, and 2) to provide additional validation for TMS as a clinical tool for Alzheimer’s Disease (AD) early detection. 135 participants were recruited from a multicenter international study in Poland and Spain, but only 47 were selected (Mean age: 68.58 ± 10.03). The sample was split according to the Erlangen Score Diagnostic Algorithm (ESA) into: CSF - (n = 11) and CSF + (n = 36). Correlations analyses between the five TMS word-list conditions and CSF biomarkers were conducted, and analysis of covariance (ANCOVA) was performed to define the effect on ESA classification in the sample, using the site of origin of the participants as covariable. Significant associations between the TMS-3 condition and Aβ42, t-tau, and p-tau were observed for the whole sample. Also, the CSF- obtained a higher cognitive performance in the TMS-3 than the possible AD group (CSF+). Our results revealed that combining CSF biomarker measures and TMS scores could contribute to a better characterization and a more precise approach to AD. Furthermore, considering that the TMS-3 condition is mostly associated with executive functions, future interventions should focus on this cognitive construct and how it could affect the patient’s ability to encode and organize the information in memory.

Aberrant lipid metabolism has been strongly linked to Alzheimer's disease (AD) pathogenesis. However, the role of lipids in the pathophysiological processes of AD and their clinical progression is unclear. We hypothesized that plasma lipids are associated with the pathological hallmarks of AD, progression from mild cognitive impairment (MCI) to AD, and the rate of cognitive decline in MCI patients. To evaluate our hypotheses, we analysed the plasma lipidome profile by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform for 213 subjects recruited consecutively: 104 AD, 89 MCI, and 20 control subjects. Forty-seven (52.8%) MCI patients progressed to AD during follow-up (58 ± 12.5 months). We found that higher plasma levels of sphingomyelin SM(36:0) and diglyceride DG(44:3) were associated with an increased risk of amyloid beta 42 (Aβ42) positivity in CSF, while levels of SM(40:1) were associated with a reduced risk. Higher plasma levels of ether-linked triglyceride TG(O-60:10) were negatively associated with pathological levels of phosphorylated tau in CSF. Plasma levels of fatty acid ester of hydroxy fatty acid FAHFA(34:0) and ether-linked phosphatidylcholine PC(O-36:1) were positively associated with pathological levels of total tau in CSF. Regarding the plasma lipids most associated with progression from MCI to AD, our analysis detected phosphatidyl-ethanolamine plasmalogen PE(P-36:4), TG(59:12), TG(46:0), and TG(O-62:7). Furthermore, TG(O-62:7) was the lipid that was most strongly associated with the rate of progression. In conclusion, our results indicate that neutral and ether-linked lipids are involved in the pathophysiological processes of AD and the progression from MCI to AD dementia, suggesting the involvement of lipid-mediated antioxidant mechanisms in AD.

Background Obstructive sleep apnoea (OSA) has a high prevalence in patients with Alzheimer’s disease (AD). Both conditions have been shown to be associated with lipid dysregulation. However, the relationship between OSA severity and alterations in lipid metabolism in the brains of patients with AD has yet to be fully elucidated. In this context, we examined the cerebrospinal fluid (CSF) lipidome of patients with suspected OSA to identify potential diagnostic biomarkers and to provide insights into the pathophysiological mechanisms underlying the effect of OSA on AD. Methods The study included 91 consecutive AD patients who underwent overnight polysomnography (PSG) to diagnose severe OSA (apnoea-hypopnea index ≥ 30/h). The next morning, CSF samples were collected and analysed by liquid chromatography coupled to mass spectrometry in an LC-ESI-QTOF-MS/MS platform. Results The CSF levels of 11 lipid species were significantly different between AD patients with ( N = 38) and without ( N = 58) severe OSA. Five lipids (including oxidized triglyceride OxTG(57:2) and four unknown lipids) were significantly correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Our analyses revealed a 4-lipid signature (including oxidized ceramide OxCer(40:6) and three unknown lipids) that provided an accuracy of 0.80 (95% CI: 0.71–0.89) in the detection of severe OSA. These lipids increased the discriminative power of the STOP-Bang questionnaire in terms of the area under the curve (AUC) from 0.61 (0.50–0.74) to 0.85 (0.71–0.93). Conclusions Our results reveal a CSF lipidomic fingerprint that allows the identification of AD patients with severe OSA. Our findings suggest that an increase in central nervous system lipoxidation may be the principal mechanism underlying the association between OSA and AD.

Background Obstructive sleep apnoea (OSA) is the most frequent form of sleep-disordered breathing in patients with Alzheimer’s disease (AD). Available evidence demonstrates that both conditions are independently associated with alterations in lipid metabolism. However, it is unknown whether the expression of lipids is different between AD patients with and without severe OSA. In this context, we examined the plasma lipidome of patients with suspected OSA, aiming to identify potential diagnostic biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Methods The study included 103 consecutive patients from the memory unit of our institution with a diagnosis of AD. The individuals were subjected to overnight polysomnography (PSG) to diagnose severe OSA (apnoea-hypopnea index ≥30/h), and blood was collected the following morning. Untargeted plasma lipidomic profiling was performed using liquid chromatography coupled with mass spectrometry. Results We identified a subset of 44 lipids (mainly phospholipids and glycerolipids) that were expressed differently between patients with AD and severe and nonsevere OSA. Among the lipids in this profile, 30 were significantly correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses revealed a 4-lipid signature (phosphatidylcholine PC(35:4), cis-8,11,14,17-eicosatetraenoic acid and two oxidized triglycerides (OxTG(58:5) and OxTG(62:12)) that provided an accuracy (95% CI) of 0.78 (0.69–0.86) in the detection of OSA. These same lipids improved the predictive power of the STOP-Bang questionnaire in terms of the area under the curve (AUC) from 0.61 (0.50–0.74) to 0.80 (0.70–0.90). Conclusion Our results show a plasma lipidomic fingerprint that allows the identification of patients with AD and severe OSA, allowing the personalized management of these individuals. The findings suggest that oxidative stress and inflammation are potential prominent mechanisms underlying the association between OSA and AD.

Study Objectives: To investigate the association between sleep and cognitive decline of patients with mild-moderate Alzheimer's disease. Methods: Observational, prospective study, including consecutive patients diagnosed with mild-moderate Alzheimer's disease. Cerebrospinal fluid was collected for amyloid-beta, total-tau, and phospho-tau levels determination. Also, overnight polysomnography was performed, followed by neuropsychological evaluations at baseline and after 12 months of follow-up. Principal component analysis revealed two profiles of patients in terms of sleep: one with a propensity to deepen the sleep (deep sleepers) and the other with a propensity to spend most of the time in the lighter sleep stage (light sleepers). Results: The cohort included 125 patients with a median [IQR] of 75.0[72.0;80.0] years. Deep and light sleepers did not present differences in relation to the cerebrospinal fluid pathological markers and to the cognitive function at the baseline. However, there was a significant difference of -1.51 (95% CI: -2.43 to -0.59) in the Mini-mental state examination after 12 months of follow-up. Accordingly, sleep depth and cognitive decline presented a dose-response relationship (p-for-trend = 0.02). Similar outcomes were observed in relation to the processing speed (Stroop words test, p-value = 0.016) and to the executive function (Verbal fluency test, p-value = 0.023). Conclusions: Considering the increased cognitive decline presented by light sleepers, the sleep profile may have a predictive role in relation to the cognitive function of patients with mild-moderate Alzheimer's disease. The modifiable nature of sleep sets this behavior as a possible useful intervention to prevent a marked cognitive decline.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized, at the neuropathological level, by the accumulation of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles formed by hyperphosphorylated tau protein. A key aspect of AD’s is focused on its early detection. In recent years, cerebrospinal fluid (CSF) has been established as a sensible and validated biomarker that could help to provide an accurate diagnosis of the disease. It is known that lower CSF Aβ-42 concentrations and higher CSF levels of total and phosphorylated tau (t-tau and p-tau respectively), have been extensively replicated parameters among AD patients. Similarly, electrophysiological signatures, as analyzed by the electroencephalography (EEG) technique, seem to be a non-invasive useful tool for evaluating the progressive loss of efficiency of neuronal networks. Given that, the purpose of this study was to explore the correlation between power EEG values derived from clusters of sensors and CSF markers in a sample of mild cognitive impairment (MCI) patients. 7 MCI participants (aged from 61 to 85) were recruited from the Cognitive Disorders Unit of the Hospital Universitari Santa Maria (Lleida, Spain). All of them underwent a neuropsychological evaluation, CSF lumbar puncture, and EEG recordings. Amyloid . Male population showed a significant negative correlation (rho = -0.754, p < 0.003) between amyloid load and theta power in antero-posterior regions of the brain. The average power of the cluster correlated significatively with ADAS (rho = 0.562, p < 0.037), total tau (rho = 0.538, p < 0.049) and delayed recall (rho = -0.612, p < 0.020). Total tau . A widespread alpha power cluster was found in the male population whose oscillatory activity correlated negatively with t-tau CSF load (rho = -0.653, p < 0.014). When assessing the female population, we found a relationship (rho = -0.864, p < 0.001) between total-tau and beta power in a widespread cluster. Additionally, the beta cluster average power significatively correlated with p-tau load (rho = -0.800, p < 0.005) and age (rho = -0.621, p < 0.041). Electrophysiological activity seems to be depicting a clear sex-based pattern of associations with neuropathological markers of AD.

Background Alzheimer’s disease (AD) is the most frequent cause of cognitive impairment. Community knowledge of the disease has proven to be a very important aspect of the development of interventions and the evaluation of their effectiveness. However, it is necessary to have standardized and recognized tools in different languages. The aim of the current study was to develop a cross-cultural adaptation of the Spanish Dementia Knowledge Assessment Scale (DKAS-S) and to assess their psychometric properties with cohorts of health students and professional and non-professional caregivers of AD patients from several regions of Spain. Methods We developed and translated the DKAS into Spanish following the forward-back-forward translation procedure. Then, we performed a cross-sectional study to assess the validity, reliability and feasibility of the DKAS-S. We also performed an analysis to obtain test-retest reliability measures. The study was performed in four medical centres across three regions in Spain. From May to September 2019, we administered the scale to students, professional and non-professional caregivers; including a subgroup of non-professional caregivers of patients with early-onset AD (< 65 years). Results Eight hundred forty-six volunteer participants completed the DKAS-S: 233 students (mean age 26.3 ± 9.2 years), 270 professional caregivers (mean age 42.5 ± 11.7 years) and 343 non-professional caregivers of AD patients. (mean age was 56.4 ± 13.16). The DKAS-S showed good internal consistency (Cronbach’s α = 0.819) and good test-retest reliability (time 1: 28.1 ± 8.09 vs time 2: 28.8 ± 7.96; t = − 1.379; p = 0.173). Sensitivity to change was also significant in a subgroup of 31 students who received education related to AD and dementias between each administration (time 1: 25.6 ± 6.03) to (time 2: 32.5 ± 7.12; t = − 5.252, p = 0.000). The validity of the construct was verified by confirmatory factor analysis, although there were challenges in the inclusion of some items in the original 4 factors. Conclusions The 25-item DKAS-S showed good psychometric properties for validity and reliability and the factorial analysis when it was administered to a population of students and professional and non-professional caregivers. It was a useful instrument for measuring levels of knowledge about dementia in Spanish population.

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease. In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography. The mean± sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of −3.36 (95% CI 0.19–0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI −1.26–4.64; p=0.445). No significant differences were found among different OSA severity groups. We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.