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Lung cancer screening (LCS) reduces lung cancer-related mortality; however, uptake remains low compared with other cancer screening programmes. In this observational study, we report the impact of timed appointments and reminders on participation in our regional LCS programme.Initial uptake of timed appointments was 53.0% (n=17 274/32 593), higher than previously reported in the UK, while initial uptake of open invitations was 29.8% (n=10 246/34 371). Among initial non-responders, 17.5% (n=4263/24 400) completed triage following a reminder. The increased participation following reminders only partially offset the significant difference in initial uptake between the two appointment types.Timed appointments and reminders are strongly advocated to increase participation in national LCS programmes.

Infants form basic expectations about their physical and social environment, as indicated by their attention toward events that violate their expectations. Yet little is known about the neuronal processing of unexpected events in the infant brain. Here, we used rhythmic visual brain stimulation in 9-month-olds (N = 38) to elicit oscillations of the theta (4 Hz) and the alpha (6 Hz) rhythms while presenting events with unexpected or expected outcomes. We found that visually entrained theta oscillations sharply increased for unexpected outcomes, in contrast to expected outcomes, in the scalp-recorded electroencephalogram. Visually entrained alpha oscillations did not differ between conditions. The processing of unexpected events at the theta rhythm may reflect learning processes such as the refinement of infants’ basic representations. Visual brain-stimulation techniques provide new ways to investigate the functional relevance of neuronal oscillatory dynamics in early brain development.

INTRODUCTION Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS Using an α‐synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α‐synuclein seeding activity in CSF in vivo. DISCUSSION Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala‐ or olfactory‐predominant LBP, for which CSF α‐synuclein SAA has low sensitivity. Highlights Cerebrospinal fluid (CSF) real‐time quaking‐induced conversion (RT‐QuIC) detects misfolded α‐synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT‐QuIC does not detect α‐synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala‐predominant variants. LBP develops late in the disease course in ADAD. CSF α‐synuclein RT‐QuIC has low sensitivity for focal, low‐burden LBP.

Introduction South Africa (SA) has the highest number of people living with HIV (PLWH) globally, and a significant burden of alcohol and other drug use (AOD). Although integrating AOD treatment into HIV care may improve antiretroviral therapy (ART) adherence, this is not typically routine practice in SA or other low‐resource settings. Identifying interventions that are feasible and acceptable for implementation is critical to improve HIV and AOD outcomes. Methods A pilot randomized hybrid type 1 effectiveness‐implementation trial (N = 61) was conducted to evaluate the feasibility and acceptability of Khanya, a task‐shared, peer‐delivered behavioral intervention to improve ART adherence and reduce AOD in HIV care in SA. Khanya was compared to enhanced treatment as usual (ETAU), a facilitated referral to on‐site AOD treatment. Implementation outcomes, defined by Proctor’s model, included feasibility, acceptability, appropriateness and fidelity. Primary pilot effectiveness outcomes were ART adherence at post‐treatment (three months) measured via real‐time electronic adherence monitoring, and AOD measured using biomarker and self‐report assessments over six months. Data collection was conducted from August 2018 to April 2020. Results and discussion Ninety‐one percent of participants (n = 56) were retained at six months. The intervention was highly feasible, acceptable, appropriate and delivered with fidelity (>90% of components delivered as intended by the peer). There was a significant treatment‐by‐time interaction for ART adherence (estimate = −0.287 [95% CI = −0.507, −0.066]), revealing a 6.4 percentage point increase in ART adherence in Khanya, and a 22.3 percentage point decline in ETAU. Both groups evidenced significant reductions in alcohol use measured using phosphatidylethanol (PEth) (F(2,101) = 4.16, p = 0.01), significantly decreased likelihood of self‐reported moderate or severe AOD (F(2,104) = 7.02, p = 0.001), and significant declines in alcohol use quantity on the timeline follow‐back (F(2,102) = 21.53, p < 0.001). Among individuals using drugs and alcohol, there was a greater reduction in alcohol use quantity in Khanya compared to ETAU over six months (F(2,31) = 3.28, p = 0.05). Conclusions Results of this pilot trial provide initial evidence of the feasibility and acceptability of the Khanya intervention for improving adherence in an underserved group at high risk for ongoing ART non‐adherence and HIV transmission. Implementation results suggest that peers may be a potential strategy to extend task‐sharing models for behavioral health in resource‐limited, global settings.

INTRODUCTION Apolipoprotein E4 (APOE4) carriers’ tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood‐brain barrier. METHODS Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment. RESULTS Levels of 24(S)‐hydroxycholesterol (24‐OHC), 27‐hydroxycholesterol (27‐OHC), and 24‐OHC/27‐OHC ratio did not differ by APOE status (p’s > 0.05). Higher 24‐OHC and 27‐OHC were associated with higher total, low density lipoprotein (LDL), non‐high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides (p’s < 0.05). Higher 24‐OHC/27‐OHC was associated with greater dementia risk (hazard ratio = 1.51, 95% confidence interval:1.02‐2.22), which interaction analyses revealed as significant for APOE3 and APOE4+, but not APOE2+ carriers. DISCUSSION Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24‐OHC/27‐OHC may contribute to dementia risk in APOE3 and APOE4+ carriers.

INTRODUCTION Platelets serve as the primary peripheral reservoir of amyloid beta (Aβ). However, there is limited research on platelet markers in routine blood examinations, particularly with regard to the large platelet ratio (P‐LCR) in Alzheimer's disease (AD). METHODS This study included 512 AD patients and 205 healthy controls (HCs). Platelet markers and apolipoprotein E (APOE) 4 status were assessed in all participants. RESULTS The study revealed that P‐LCR was significantly elevated in AD patients compared to HCs. In AD patients carrying APOE4, P‐LCR significantly negatively correlated with Montreal Cognitive Assessment scores. There was an observed increasing trend in the rate of change in P‐LCR with disease progression. Binary logistic regression analysis indicated that P‐LCR may constitute a risk factor for AD, after adjusting for age, sex, APOE4, and body mass index. DISCUSSION P‐LCR is associated with disease severity in AD patients carrying APOE4. P‐LCR may be a promising marker to reflect platelet activity in AD patients. Highlights P‐LCR significantly negatively correlated with MoCA scores in AD patients with APOE4. The rate of change in P‐LCR showed an increasing trend with disease progression. P‐LCR may be a risk factor for AD.

INTRODUCTION We assessed a genetic risk score for Alzheimer's disease (AD‐GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial. METHODS 1260 at‐risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N = 126 participants underwent magnetic resonance imaging (MRI), and N = 47 positron emission tomography (PET) scans (Pittsburgh Compund B [PiB], Fluorodeoxyglucose) at baseline; N = 107 and N = 38 had repeated 2‐year scans. RESULTS The APOE4 allele, but not AD‐GRS, was associated with baseline lower hippocampus volume (β = −0.27, p = 0.001), greater amyloid deposition (β = 0.48, p = 0.001), 2‐year decline in hippocampus (β = −0.27, p = 0.01), total gray matter volume (β = −0.25, p = 0.01), and cortical thickness (β = −0.28, p = 0.003). In analyses stratified by AD‐GRS (below vs above median), the PiB composite score increased less in intervention versus control in the higher AD‐GRS group (β = −0.60, p = 0.03). DISCUSSION AD‐GRS and APOE4 may have different impacts on potential intervention effects on amyloid, that is, less accumulation in the higher‐risk group (AD‐GRS) versus lower‐risk group (APOE). Highlights First study of neuroimaging and AD genetics in a multidomain lifestyle intervention. Possible intervention effect on brain amyloid deposition may rely on genetic risk. AD‐GRS and APOE4 allele may have different impacts on amyloid during intervention.

INTRODUCTION Glial fibrillary acidic protein (GFAP) in plasma is a proxy for astrocytic activity and is elevated in amyloid‐β (Aβ)‐positive individuals, making GFAP a potential blood‐based biomarker for Alzheimer's disease (AD). METHODS We assessed plasma GFAP in 72 Aβ‐positive participants diagnosed with the visual or language variant of AD who underwent Aβ‐ and tau‐PET. Fifty‐nine participants had follow‐up imaging. Linear regression was applied on GFAP and imaging quantities. RESULTS GFAP did not correlate with Aβ‐ or tau‐PET cross‐sectionally. There was a limited positive correlation between GFAP and rates of tau accumulation, particularly in the language variant of AD, although associations were weaker after removing one outlier patient with the highest GFAP level. DISCUSSION Among Aβ‐positive AD participants with atypical presentations, plasma GFAP did not correlate with levels of AD pathology on PET, suggesting that the associations between GFAP and AD pathology might plateau during the advanced phase of the disease.

Introduction Ethnoracial differences in cerebrospinal fluid (CSF; amyloid beta 42 [Aβ42], total tau [t‐tau], phosphorylated tau 181 [p‐tau181], and plasma (p‐tau181, neurofilament light [NfL]) biomarkers of Alzheimer's disease (AD) are incompletely understood. Methods We performed cross‐sectional analyses with and without adjustment for covariates comparing baseline CSF (Aβ42, t‐tau, p‐tau181) and plasma (p‐tau181, NfL) values in 47 African Americans (AAs) matched to 141 non‐Hispanic Whites (NHWs) and 43 Latinos (LAs) matched to 129 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results Unadjusted comparisons revealed no significant differences in plasma or CSF biomarkers between AAs and NHWs. A trend toward a lower CSF t‐tau and p‐tau181 in LAs compared to NHWs was observed, without significant differences in plasma biomarkers. After adjusting for covariates, there were no significant differences in CSF or plasma biomarkers between AAs and NHWs or between LAs and NHWs. Discussion Plasma and CSF AD biomarkers may perform similarly across diverse populations but future studies in large, diverse cohorts are needed.