Structures of the Hepaci-, Pegi-, and Pestiviruses envelope proteins suggest a novel membrane fusion mechanism.

Enveloped viruses encode specialised glycoproteins that mediate fusion of viral and host membranes. Discovery and understanding of the molecular mechanisms of fusion have been achieved through structural analyses of glycoproteins from many different viruses, and yet the fusion mechanisms of some viral genera remain unknown. We have employed systematic genome annotation and AlphaFold modelling to predict the structures of the E1E2 glycoproteins from 60 viral species in the Hepacivirus, Pegivirus, and Pestivirus genera. While the predicted structure of E2 varied widely, E1 exhibited a very consistent fold across genera, despite little or no similarity at the sequence level. Critically, the structure of E1 is unlike any other known viral glycoprotein. This suggests that the Hepaci-, Pegi-, and Pestiviruses may possess a common and novel membrane fusion mechanism. Comparison of E1E2 models from various species reveals recurrent features that are likely to be mechanistically important and sheds light on the evolution of membrane fusion in these viral genera. These findings provide new fundamental understanding of viral membrane fusion and are relevant to structure-guided vaccinology.

Removing independent noise in systems neuroscience data using DeepInterpolation.

Progress in many scientific disciplines is hindered by the presence of independent noise. Technologies for measuring neural activity (calcium imaging, extracellular electrophysiology and functional magnetic resonance imaging (fMRI)) operate in domains in which independent noise (shot noise and/or thermal noise) can overwhelm physiological signals. Here, we introduce DeepInterpolation, a general-purpose denoising algorithm that trains a spatiotemporal nonlinear interpolation model using only raw noisy samples. Applying DeepInterpolation to two-photon calcium imaging data yielded up to six times more neuronal segments than those computed from raw data with a 15-fold increase in the single-pixel signal-to-noise ratio (SNR), uncovering single-trial network dynamics that were previously obscured by noise. Extracellular electrophysiology recordings processed with DeepInterpolation yielded 25% more high-quality spiking units than those computed from raw data, while DeepInterpolation produced a 1.6-fold increase in the SNR of individual voxels in fMRI datasets. Denoising was attained without sacrificing spatial or temporal resolution and without access to ground truth training data. We anticipate that DeepInterpolation will provide similar benefits in other domains in which independent noise contaminates spatiotemporally structured datasets.

The Mediterranean dietary pattern for optimising health and performance in competitive athletes: a narrative review.

Nutrition plays a key role in training for, and competing in, competitive sport, and is essential for reducing risk of injury and illness, recovering and adapting between bouts of activity, and enhancing performance. Consumption of a Mediterranean diet (MedDiet) has been demonstrated to reduce risk of various non-communicable diseases and increase longevity. Following the key principles of a MedDiet could also represent a useful framework for good nutrition in competitive athletes under most circumstances, with potential benefits for health and performance parameters. In this review, we discuss the potential effects of a MedDiet, or individual foods and compounds readily available in this dietary pattern, on oxidative stress and inflammation, injury and illness risk, vascular and cognitive function, and exercise performance in competitive athletes. We also highlight potential modifications which could be made to the MedDiet (whilst otherwise adhering to the key principles of this dietary pattern) in accordance with contemporary sports nutrition practices, to maximise health and performance effects. In addition, we discuss potential directions for future research.

Addressing health disparities in hispanic communities through an innovative team-based medical spanish program at the medical school level - a single-institution study.

BACKGROUND: There are insufficient Spanish-speaking physicians to effectively serve a large and rapidly growing Spanish-speaking patient population. METHODS: A team-based hybrid medical Spanish program was designed and implemented at a single medical school in Southern California. This pilot program consisted of a weekly in-person portion where students reviewed Spanish vocabulary and grammar and practiced clinical encounters in teams through active role play. Students supplemented in-class learning with online coursework. Program success was measured through physician-evaluated clinical encounters with Spanish-speaking standardized patients, a 100-question multiple-choice exam, and pre- and post-program surveys. RESULTS: 97% of students in the program (n = 32) received a passing grade at program completion. Student surveys demonstrated enthusiasm and engagement in weekly sessions (95% overall attendance, 97% reported feeling either excited or ready to learn prior to class). In a post-program survey, 100% of students felt better suited and increased desire to treat Hispanic patients. Additionally, all students indicated an interest in the continued use of Spanish in both their schooling and future practice. In a follow-up survey after three months of clinical experience in their 3rd year of medical school, 100% of students reported that medical Spanish is "very beneficial" in patient care and that students with medical Spanish proficiency have advantages over non-speaking students when it comes to patient care opportunities. 100% felt that time spent learning medical Spanish during pre-clinical years was time well spent and that the medical Spanish program enhanced their care of Spanish-speaking students. CONCLUSIONS: The results of the pilot program show a significant increase in the ability of students to engage in clinical interaction in Spanish. The results of our study demonstrate a significant increase in the knowledge, clinical skills, and self-reported confidence of students to treat Hispanic patients. Furthermore, all students not only felt better equipped and more confident to treat Hispanic patients, but they also had an increased desire to do so moving forward in their careers. We conclude that an effective medical Spanish program can be executed simultaneously with a pre-clinical medical school curriculum.

Relationship between urinary nitrate concentrations and cognitive function in older adults: findings from the NHANES survey.

This study evaluated the association of urinary nitrate concentrations with cognition in older subjects enrolled in the NHANES study. We also explored whether associations between urinary nitrate and cognition were modified by cardiovascular risk, vitamin D status and vitamin C intake. Two NHANES cycles were merged (2011-2012 and 2013-2014) and a total of 1,015 adults aged 60-80 (69.4 ± 0.3) years were included. Cognition was assessed using the Word List Learning, Word List Recall, Animal Fluency and the Digit Symbol Substitution tests. Urinary nitrate was analysed using electrospray tandem mass spectrometry. Urinary nitrate concentrations were not associated with cognitive performance on any of the cognitive tests. Associations were also not significant in subjects at greater risk for cognitive impairment (i.e. high cardiovascular risk and non-optimal vitamin D status). Longitudinal analyses are needed to explore the associations of urinary nitrate concentrations with dietary nitrate intake and cognitive function.

Structure-function analyses of two plant meso-diaminopimelate decarboxylase isoforms reveal that active-site gating provides stereochemical control.

meso-Diaminopimelate decarboxylase catalyzes the decarboxylation of meso-diaminopimelate, the final reaction in the diaminopimelate l-lysine biosynthetic pathway. It is the only known pyridoxal-5-phosphate-dependent decarboxylase that catalyzes the removal of a carboxyl group from a d-stereocenter. Currently, only prokaryotic orthologs have been kinetically and structurally characterized. Here, using complementation and kinetic analyses of enzymes recombinantly expressed in Escherichia coli, we have functionally tested two putative eukaryotic meso-diaminopimelate decarboxylase isoforms from the plant species Arabidopsis thaliana We confirm they are both functional meso-diaminopimelate decarboxylases, although with lower activities than those previously reported for bacterial orthologs. We also report in-depth X-ray crystallographic structural analyses of each isoform at 1.9 and 2.4 Å resolution. We have captured the enzyme structure of one isoform in an asymmetric configuration, with one ligand-bound monomer and the other in an apo-form. Analytical ultracentrifugation and small-angle X-ray scattering solution studies reveal that A. thaliana meso-diaminopimelate decarboxylase adopts a homodimeric assembly. On the basis of our structural analyses, we suggest a mechanism whereby molecular interactions within the active site transduce conformational changes to the active-site loop. These conformational differences are likely to influence catalytic activity in a way that could allow for d-stereocenter selectivity of the substrate meso-diaminopimelate to facilitate the synthesis of l-lysine. In summary, the A. thaliana gene loci At3g14390 and At5g11880 encode functional. meso-diaminopimelate decarboxylase enzymes whose structures provide clues to the stereochemical control of the decarboxylation reaction catalyzed by these eukaryotic proteins.

Differences in circulating appetite-related hormone concentrations between younger and older adults: a systematic review and meta-analysis.

Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.

Tissue segmentation-based electron density mapping for MR-only radiotherapy treatment planning of brain using conventional T1-weighted MR images.

PURPOSE: Magnetic resonance imaging (MRI) is the primary modality for targeting brain tumors in radiotherapy treatment planning (RTP). MRI is not directly used for dose calculation since image voxel intensities of MRI are not associated with EDs of tissues as those of computed tomography (CT). The purpose of the present study is to develop and evaluate a tissue segmentation-based method to generate a synthetic-CT (sCT) by mapping EDs to corresponding tissues using only T1-weighted MR images for MR-only RTP. METHODS: Air regions were contoured in several slices. Then, air, bone, brain, cerebrospinal fluid (CSF), and other soft tissues were automatically segmented with an in-house algorithm based on edge detection and anatomical information and relative intensity distribution. The intensities of voxels in each segmented tissue were mapped into their CT number range to generate a sCT. Twenty-five stereotactic radiosurgery and stereotactic ablative radiotherapy patients' T1-weighted MRI and coregistered CT images from two centers were retrospectively evaluated. The CT was used as ground truth. Distances between bone contours of the external skull of sCT and CT were measured. The mean error (ME) and mean absolute error (MAE) of electron density represented by standardized CT number was calculated in HU. RESULTS: The average distance between the contour of the external skull in sCT and the contour in coregistered CT is 1.0 ± 0.2 mm (mean ± 1SD). The ME and MAE differences for air, soft tissue and whole body voxels within external body contours are -4 HU/24 HU, 2 HU/26 HU, and -2 HU/125 HU, respectively. CONCLUSIONS: A MR-sCT generation technique was developed based on tissue segmentation and voxel-based tissue ED mapping. The generated sCT is comparable to real CT in terms of anatomical position of tissues and similarity to the ED assignment. This method provides a feasible method to generate sCT for MR-only radiotherapy treatment planning.

Physiological and performance effects of nitrate supplementation during roller-skiing in normoxia and normobaric hypoxia.

The present study examined the effects of acute nitrate (NO3-) supplementation ingested in the form of concentrated beetroot juice on cross-country roller-ski performance in normoxia (N) and normobaric hypoxia (H). Eight competitive cross-country skiers (five males: age 22 ± 3 years, V·O2max 71.5 ± 4.7 mL kg-1·min-1; three females: age 21 ± 1 years, V·O2max 58.4 ± 2.5 mL kg-1·min-1) were supplemented with a single dose of NO3--rich beetroot juice (BRJ, ∼13 mmol NO3-) or a NO3--depleted placebo (PL, ∼0 mmol NO3-) and performed 2 x 6-min submaximal exercise bouts and a 1000-m time-trial (TT) on a treadmill in N (20.9% O2) or H (16.8% O2). The four experimental trials were presented in a randomised, counter-balanced order. Plasma NO3- and nitrite concentrations were significantly higher following BRJ compared to PL (both p < 0.001). However, respiratory variables, heart rate, blood lactate concentration, ratings of perceived exertion, and near-infrared spectroscopy-derived measures of muscle tissue oxygenation during submaximal exercise were not significantly different between BRJ and PL (all p > 0.05). Likewise, time to complete the TT was unaffected by supplementation in both N and H (p > 0.05). In conclusion, an acute dose of ∼13 mmol NO3- does not affect physiological or performance responses to submaximal or maximal treadmill roller-skiing in competitive cross-country skiers exercising in N and H.

Dietary nitrate supplementation enhances short but not longer duration running time-trial performance.

PURPOSE: This study evaluated the effects of dietary nitrate (NO3-) supplementation on physiological functioning and exercise performance in trained runners/triathletes conducting short and longer-distance treadmill running time-trials (TT). METHOD: Eight trained male runners or triathletes completed four exercise performance tests comprising a 10 min warm up followed by either a 1500 or 10,000 m treadmill TT. Exercise performance tests were preceded 3 h before the exercise by supplementation with either 140 ml concentrated nitrate-rich (~12.5 mmol nitrate) (BRJ) or nitrate-deplete (~0.01 mmol nitrate) (PLA) beetroot juice. RESULTS: BRJ supplementation significantly elevated plasma [NO2-] (P < 0.05). Resting blood pressure and exercise [Formula: see text] were not significantly different between BRJ and PLA (P > 0.05). However, post-exercise blood [lactate] was significantly greater in BRJ following the 1500 m TT (6.6 ± 1.2 vs. 6.1 ± 1.5 mM; P < 0.05), but not significantly different between conditions in the 10,000 m TT (P > 0.05). Performance in the 1500 m TT was significantly faster in BRJ vs. PLA (319.6 ± 36.2 vs. 325.7 ± 38.8 s; P < 0.05). Conversely, there was no significant difference in 10,000 m TT performance between conditions (2643.1 ± 324. 1 vs. 2649.9 ± 319.8 s, P > 0.05). CONCLUSION: Acute BRJ supplementation significantly enhanced 1500 m, but not 10,000 m TT performance. These findings suggest that BRJ might be ergogenic during shorter distance TTs which allow for a high work rate, but not during longer distance TTs, completed at a lower work rate.

Effect of Dietary Nitrate Supplementation on Swimming Performance in Trained Swimmers.

Nitrate supplementation appears to be most ergogenic when oxygen availability is restricted and subsequently may be particularly beneficial for swimming performance due to the breath-hold element of this sport. This represents the first investigation of nitrate supplementation and swimming time-trial (TT) performance. In a randomized double-blind repeated-measures crossover study, ten (5 male, 5 female) trained swimmers ingested 140ml nitrate-rich (~12.5mmol nitrate) or nitrate-depleted (~0.01mmol nitrate) beetroot juice. Three hours later, subjects completed a maximal effort swim TT comprising 168m (8 × 21m lengths) backstroke. Preexercise fractional exhaled nitric oxide concentration was significantly elevated with nitrate compared with placebo, Mean (SD): 17 (9) vs. 7 (3)p.p.b., p = .008. Nitrate supplementation had a likely trivial effect on overall swim TT performance (mean difference 1.22s; 90% CI -0.18-2.6s; 0.93%; p = .144; d = 0.13; unlikely beneficial (22.6%), likely trivial (77.2%), most unlikely negative (0.2%)). The effects of nitrate supplementation during the first half of the TT were trivial (mean difference 0.29s; 90% CI -0.94-1.5s; 0.46%; p = .678; d = 0.05), but there was a possible beneficial effect of nitrate supplementation during the second half of the TT (mean difference 0.93s; 90% CI 0.13-1.70s; 1.36%; p = .062; d = 0.24; possibly beneficial (63.5%), possibly trivial (36.3%), most unlikely negative (0.2%)). The duration and speed of underwater swimming within the performance did not differ between nitrate and placebo (both p > .30). Nitrate supplementation increased nitric oxide bioavailability but did not benefit short-distance swimming performance or the underwater phases of the TT. Further investigation into the effects of nitrate supplementation during the second half of performance tests may be warranted.

Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness.

Nitrate-rich beetroot juice (BRJ) increases plasma nitrite concentrations, lowers the oxygen cost (V⋅O2) of steady-state exercise and improves exercise performance in sedentary and moderately-trained, but rarely in well-trained individuals exercising at sea-level. BRJ supplementation may be more effective in a hypoxic environment, where the reduction of nitrite into nitric oxide (NO) is potentiated, such that well-trained and less well-trained individuals may derive a similar ergogenic effect. We conducted a randomised, counterbalanced, double-blind placebo controlled trial to determine the effects of BRJ on treadmill running performance in moderate normobaric hypoxia (equivalent to 2500 m altitude) in participants with a range of aerobic fitness levels. Twelve healthy males (V⋅O2max ranging from 47.1 to 76.8 ml kg(-1) min(-1)) ingested 138 ml concentrated BRJ (∼15.2 mmol nitrate) or a nitrate-deplete placebo (PLA) (∼0.2 mmol nitrate). Three hours later, participants completed steady-state moderate intensity running, and a 1500 m time-trial (TT) in a normobaric hypoxic chamber (FIO2 âˆ¼ 15%). Plasma nitrite concentration was significantly greater following BRJ versus PLA 1 h post supplementation, and remained higher in BRJ throughout the testing session (p < 0.01). Average V⋅O2 was significantly lower (BRJ: 18.4 ± 2.0, PLA: 20.4 ± 12.6 ml kg(-1) min(-1); p = 0.002), whilst arterial oxygen saturation (SpO2) was significantly greater (BRJ: 88.4 ± 2.7, PLA: 86.5 ± 3.3%; p < 0.001) following BRJ. BRJ improved TT performance in all 12 participants by an average of 3.2% (BRJ: 331.1 ± 45.3 vs. PL: 341.9 ± 46.1 s; p < 0.001). There was no apparent relationship between aerobic fitness and the improvement in performance following BRJ (r(2) = 0.05, p > 0.05). These findings suggests that a high nitrate dose in the form of a BRJ supplement may improve running performance in individuals with a range of aerobic fitness levels conducting moderate and high-intensity exercise in a normobaric hypoxic environment.

Fatty acids and the risk of death during acute myocardial ischaemia.

Plasma free fatty acids (non-esterified fatty acids) increase in the first hour of the onset of acute myocardial ischaemia. This results from catecholamine stimulation of adipose tissue lipolysis. It can lead to a metabolic crisis in the injured myocardium with the development of ventricular arrhythmias and increased early mortality. Preconditioning, ß-adrenergic blockade and glucose-insulin-potassium are possible therapeutic approaches, but anti-lipolytic agents, such as some nicotinic acid derivatives, can reduce plasma free fatty acid concentrations within minutes and have untried potential. A clinical trial of their effectiveness is needed from the first moment when a patient with an acute coronary syndrome is seen by paramedics.

Quantitative, three-dimensional imaging of aluminum drop combustion in solid propellant plumes via digital in-line holography.

Burning aluminized propellants eject reacting molten aluminum drops with a broad size distribution. Prior to this work, in situ measurement of the drop size statistics and other quantitative flow properties was complicated by the narrow depth-of-focus of microscopic videography. Here, digital in-line holography (DIH) is demonstrated for quantitative volumetric imaging of the propellant plume. For the first time, to the best of our knowledge, in-focus features, including burning surfaces, drop morphologies, and reaction zones, are automatically measured through a depth spanning many millimeters. By quantifying all drops within the line of sight, DIH provides an order of magnitude increase in the effective data rate compared to traditional imaging. This enables rapid quantification of the drop size distribution with limited experimental repetition.

Beyond Hypertension: Examining Variable Blood Pressure's Role in Cognition and Brain Structure.

OBJECTIVES: Hypertension or high blood pressure (BP) is one of the twelve modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although hypertension is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain changes. This study examined the relationship between variable BP and longitudinal cognitive, white matter hyperintensity (WMH), gray matter (GM), and white matter (WM) volume change over time and post-mortem neuropathology. METHODS: A total of 4,606 participants (32,776 follow-ups) from RADC Research Resource Sharing Hub (RUSH) and 2,114 participants (9,827 follow-ups) from Alzheimer's Disease Neuroimaging Initiative (ADNI) were included. Participants were divided into one of three groups: normal, high, or variable BP. Linear mixed models investigated the relationship between BP and cognition, brain structure, and neuropathology. RESULTS: Older adults with variable BP exhibited the highest rate of cognitive decline followed by high and then normal BP. Increased GM volume loss and WMH burden was also observed in variable compared to high and normal BP. In post-mortem neuropathology, both variable and high BP had increased rates compared to normal BP. All the results were consistent across the RUSH and ADNI participants, supporting the generalizability of the findings. DISCUSSION: Damages potentially associated with variable BP may reduce resilience to future dementia related pathology and increased risk of dementia more than that caused by high BP. Improved treatment and management of variable BP may help reduce cognitive decline in the older adult population.

Beyond Hypertension: Examining Variable Blood Pressure's Role in Cognition and Brain Structure.

Importance: Hypertension is a known risk factor for cognitive decline and structural brain changes in aging and dementia. In addition to high blood pressure (BP), individuals may also experience variable BP, meaning that their BP fluctuates between normal and high. It is currently unclear what the effects of variable BP are on cognition and brain structure. Objective: To investigate the influence of BP on cognition and brain structure in older adults. Design Setting and Participants: This longitudinal cohort study included data from the Rush Alzheimer's Disease Center Research Resource Sharing Hub (RUSH) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants from the two studies were included if they had BP measurements and either cognitive scores or MRI scans from at least one visit. Main Outcomes and Measures: Longitudinal gray matter, white matter, white matter hyperintensity volumes, postmortem neuropathology information, as well as cognitive test scores. Results: A total of 4606 participants (3429 females, mean age = 76.8) with 32776 follow-ups (mean = 7 years) from RUSH and 2114 participants (1132 females, mean age = 73.3) with 9827 follow-ups (mean = 3 years) from ADNI were included in this study. Participants were divided into one of three groups: 1) normal BP, high BP, or variable BP. Older adults with variable BP exhibited the highest rate of cognitive decline followed by high BP and then normal BP. Increased GM volume loss and WMH burden was also observed in variable BP compared to high and normal BP. With respect to post-mortem neuropathology, both variable and high BP had increased severities compared to normal BP. Importantly, results were consistent across the RUSH and ADNI participants, supporting the generalizability of the findings. Conclusion and Relevance: Limited research has examined the long-term impact of variable BP on cognition and brain structure. These findings show the importance that both high and variable BP have on cognitive decline and structural brain changes. Structural damages caused by variable BP may reduce resilience to future dementia-related pathology and increased risk of dementia. Improved treatment and management of variable BP may help reduce cognitive decline in the older adult population.

The influence of APOE status on rate of cognitive decline.

BACKGROUND: Apolipoprotein (APOE) ɛ4 positivity and subjective cognitive decline (SCD) both increase risk of Alzheimer's disease (AD) development. However, few studies have examined the relationship between SCD and APOE status, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD and mild cognitive impairment (MCI). METHODS: A sample of 3494 older adults (1990 normal controls, NC, 775 SCD, and 729 MCI) with a mean follow-up of 9.09 years were included from the Rush Alzheimer's Disease Center Research Sharing Hub. Linear mixed effects models examined the relationship between APOE status and cognitive change in older adults with SCD normal controls, and people with MCI. RESULTS: The presence of at least one ɛ2 allele in SCD and MCI results in cognitive change rates similar to a NC with the ɛ3ɛ3 genotype. Older adult SCD-ɛ4 individuals exhibited increased rate of cognitive decline compared to all groups, including NC-ɛ4 and MCI-ɛ4. CONCLUSION: People with SCD with at least one ɛ4 allele experience increased rates of cognitive decline compared to cognitively healthy older adults and people with MCI. These findings have important implications for treatments and interventions and can improve future research and clinical trials by targeting people in the preclinical AD phase (i.e., SCD) who also possess at least one APOE ɛ4 allele.

Subjective Cognitive Decline Is Associated With Lower Baseline Cognition and Increased Rate of Cognitive Decline.

OBJECTIVES: Subjective cognitive decline (SCD) is a known risk factor for Alzheimer's disease. However, little research has examined whether healthy older adults with SCD (SCD+) exhibit lower cognition and increased rates of cognitive decline compared to those without SCD (SCD-). The goal of this study was to examine if cognitive change over a 15-year period differs between SCD+ and SCD-. METHOD: 3,019 cognitively normal older adults (831 SCD+) from 3 Rush Alzheimer's Disease Center cohort studies were followed annually for up to a maximum of 15 years. Due to attrition, the average follow-up time was 5.7 years. Cognition was measured using z-scores of global cognition, episodic memory, semantic memory, perceptual speed, visuospatial ability, and working memory. Linear mixed-effects models investigated whether SCD was associated with cognitive change. RESULTS: Both baseline cognition and cognitive change over time differed between SCD+ and SCD-. People with SCD+ exhibited lower baseline scores and a steeper decline in global cognition, episodic memory, semantic memory, and perceptual speed. People with SCD+ did not differ from SCD- in baseline visuospatial ability or working memory but exhibited increased change over time in those two domains compared to SCD-. DISCUSSION: The observed results reveal that older adults with SCD+ have lower baseline cognition and steeper declines in cognition over time compared to SCD-. Older adults with SCD may be aware of subtle cognitive declines that occur over time in global cognition, episodic memory, semantic memory, perceptual speed, visuospatial ability, and working memory compared to those without SCD.