Kirsty Lu

Females typically perform slightly better than males on memory tests, but this may be partially explained by gender-related biases in remembering the test content. Sex/gender-related differences are underexplored on tests designed to detect subtle Alzheimer's disease-related memory impairment. We studied sex differences on memory tests among older adults, particularly focusing on the Face-Name test (FNAME-12). Specifically, we investigated whether participants were biased toward remembering stimuli that matched their own sex. Cognitively normal participants (n = 452) completed cognitive tests including FNAME-12 at baseline (aged ∼70 years) and follow-up (aged ∼73). FNAME-12 stimuli comprise male and female faces, with names and occupations. Recall and recognition were tested with delays of up to 7 days. We investigated how FNAME-12 outcomes were affected by stimulus gender and participant sex. We examined correlations between "gender bias scores" at baseline and follow-up. Women outperformed men on memory tests including FNAME-12. Men and women recalled more male than female stimuli, with this discrepancy being two to three times greater among men (baseline: men d = 0.52, women d = 0.15; follow-up: men d = 0.58, women d = 0.25). Seven-day retention rates for male stimuli were higher (recall d = 0.32; recognition d = 0.41). Baseline and follow-up "gender bias scores" were weakly to moderately correlated. We observed a gender bias on FNAME-12-particularly among male participants-where male stimuli were better remembered than female stimuli. This bias showed some consistency over ∼2.5 years. Sex differences on memory tests require careful interpretation, as they may be partially explained by gender-related bias in the learning and recall of test content. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

In Alzheimer’s disease (AD), accelerated long-term forgetting (ALF), where information is retained normally over 10–30 min but lost at an accelerated rate over subsequent days to weeks, develops several years before symptom onset. However, the neuroanatomical changes underpinning ALF remain undetermined. Eighteen presymptomatic autosomal dominant AD mutation carriers and 12 non-carriers underwent ALF assessment with a list, a story, and visual figure, testing 30-min and 7-day recall of each, separately. T1 and diffusion-weighted MRI were acquired. Cortical thickness was estimated for 13 pre-defined grey matter regions, with streamline tractography assessing associated structural connectivity. In mutation carriers, lower verbal ALF performance (list and story) was strongly associated with thinner prefrontal cortex (PFC) across four contiguous regions bilaterally. This association was absent in non-carriers. No associations were found between ALF and the thickness/volume of medial temporal lobe (MTL) structures. The association between ALF and PFC connectivity was weaker than for cortical thickness. Our results suggest that early subtle pathological change in PFC underpins ALF development, highlighting the central role of PFC dysfunction in very early AD-related cognitive decline. ALF may represent a qualitatively different (non-MTL driven) form of forgetting compared with the short interval forgetting that develops at later disease stages.

Background In Alzheimer’s disease (AD), sensitive measures of cognitive decline prior to overt symptoms are urgently needed. Accelerated long-term forgetting (ALF), where new information is retained normally over conventional testing intervals but is then lost at an accelerated rate over the following days and weeks, has been identified cross-sectionally in presymptomatic autosomal dominant and sporadic AD cohorts. We aimed to assess whether ALF testing is predictive of proximity to future symptom onset. Methods 20 asymptomatic autosomal dominant AD mutation carriers who performed normally on standard cognitive testing underwent ALF assessment with (1) a list, (2) a story and (3) a visual figure, with the testing of 30-min recall and 7-day recall. Participants were followed up annually for a median of 7 years and assessed each time with the Clinical Dementia Rating (CDR) scale. Results 9/20 participants developed symptoms (CDR global>0) during follow-up. Those who became symptomatic had lower baseline ALF scores for both the list (progressors=30 (IQR, 30–36.4) and non-progressors=58.3 (IQR, 33–66.7), p=0.03) and story (progressors=58.8 (IQR, 44–66) and non-progressors=81.2 (IQR, 69.1–87.8), pConclusions Severity of ALF is not only associated with the presence of AD pathology but also predictive of clinical onset, identifying those at the highest risk of imminent decline. ALF testing offers promise in aiding presymptomatic trial recruitment, as a presymptomatic cognitive endpoint and potentially as a screening tool in the wider population.

Sleep and circadian disturbances are associated with increased dementia risk. The mechanism remains poorly understood. We aimed to examine the relationship between night/shift working at age 31 and biomarkers of late-life brain health and to estimate the extent to which these relationships are mediated by unhealthy lifestyle behaviours. A prospective longitudinal cohort study, Insight 46, recruited participants from the Medical Research Council National Survey of Health and Development (NSHD) 1946 British Birth cohort. All born in the same week in 1946, participants were assessed at age 70 with multi-modal structural and molecular brain imaging and fluid biomarkers, from which whole-brain and hippocampal volumes, white matter hyper-intensity volume (WMHV), 18F-florbetapir amyloid-β PET Centiloids and plasma phosphorylated tau (p-tau)217 were derived. Prospective data collection included night/shift working at age 31, alongside smoking, alcohol intake, body mass index, exercise, blood pressure, Framingham risk score (FRS) at multiple timepoints from age 20 to 70 and dementia diagnosis or death by age 78. Analyses were adjusted for sex, age, education, socioeconomic position and, where appropriate, total intracranial volume or apolipoprotein E (APOE) genotype. Night/shift working data were available for 431 Insight 46 participants {50% female, mean age 70.7 years [standard deviation (SD) 0.6]}. Night/shift workers had lower whole-brain volume [−19.9 mL, 95% confidence interval (CI) −31.9, −7.9, P = 0.001], lower amyloid PET Centiloids (−9.45, 95% CI −14.7, −4.1, P = 0.0008) and lower plasma p-tau217 concentration (−0.05 pg/mL, 95% CI −0.10, −0.001, P = 0.04), without significant difference in hippocampal volume or WMHV. p-tau217 concentrations were also lower in night/shift workers from a wider sample from the NSHD cohort [n = 1067, mean age 69.9 (SD 0.7), −0.05 pg/mL, 95% CI −0.08, −0.02, P = 0.004]. By age 78, night/shift workers in the NSHD cohort (n = 3040) had lower rates of all-cause (excluding vascular) dementia (hazard ratio 0.33, 95% CI 0.12, 0.92, P = 0.03). Night/shift workers had 0.6% higher FRS (P = 0.01) at age 36, smoked 5.9 more pack-years by age 53 (P = 0.005), consumed 10.7 g/day more alcohol by age 63 (P = 0.006) and had higher rates of APOE ɛ4 allele carriage. Lifestyle behaviours mediated 28% of the lower brain volume in night/shift workers. Despite less healthy lifestyles, higher rates of APOE ɛ4 allele carriage and smaller brains, night/shift workers had lower levels of Alzheimer’s disease pathology as measured by amyloid PET and plasma p-tau217 and approximately one-third of the risk of dementia by age 78 compared with non-night/shift workers. Lower brain volume in night/shift workers was partially mediated by unhealthy behaviours. Reduced dementia risk in night/shift workers is unexpected and will require further study.

Higher HbA1c in mid-to-later life has been associated with smaller whole brain volume (WBV) in older women but not men. We explored whether this association was replicated using different markers of (i) glycaemic health [fasting glucose, insulin resistance (HOMA2-IR), and β-cell function (HOMA-%B)] and (ii) brain structure (white or grey matter volume). 453 participants (51% men) from the 1946 British Birth Cohort had glycaemic measures (at age 60–64) and MRI measures (at age ∼70). In women, higher fasting glucose and insulin resistance at age ∼60 were weakly associated with lower WBV at age ∼70 [eg, fasting glucose: β* = −0.07 (95% CI: −0.13, −0.01), P = .02]. No associations emerged for men for any glycaemic marker. HOMA-%B was not associated with brain outcomes in either sex. Women's later-life brain health may be more vulnerable to midlife hyperglycaemia.

We assessed the association between leisure time physical activity patterns across 30 years of adulthood with a range of in vivo Alzheimer’s disease-related neurodegenerative markers and cognition, and their interplay, at age 70. Participants from the 1946 British birth cohort study prospectively reported leisure time physical activity five times between ages 36 and 69 and were dichotomized into (i) not active (no participation/month) and (ii) active (participated once or more/month) and further derived into: (0) never active (not active); (1) active before 50’s only (≤43 years); (2) active from 50’s onwards only (≥53 years); (3) always active (active throughout). Participants underwent 18F-florbetapir Aβ and magnetic resonance imaging at age 70. Regression analyses were conducted to assess the direct and the moderating relationship between leisure time physical activity metrics, Alzheimer’s disease-related neurodegeneration markers (including Aβ status, hippocampal and whole-brain volume, and cortical thickness in Alzheimer’s disease signature regions) and cognition. All models were adjusted for childhood cognition, education and childhood socioeconomic position, and examined by sex. Findings drawn from 468 participants (49% female) demonstrated a direct association between being active before 50 years old (≤43 years) and throughout life (up to age 69 years), with larger hippocampal volume at age 70 (P < 0.05). There was little evidence that leisure time physical activity had direct effects on other brain health measures (all P > 0.05). However, leisure time physical activity patterns modified and attenuated the association between poorer cognitive functioning at age 70 and a range of Alzheimer’s disease-related neurodegenerative markers (Aβ status; hippocampal and whole-brain volume; cortical thickness in Alzheimer’s disease regions) (all P < 0.05). We found suggestive evidence that women with early markers of Alzheimer’s disease-related neurodegeneration were most sensitive to leisure time physical activity patterns: a lifetime of inactivity in women exacerbated the manifestation of early Alzheimer’s disease markers (Aβ and cortical thickness-related cognition), yet, if women were active across life or early in life, it mostly buffered these negative relationships. Engagement in leisure time physical activity in the life course is associated with better cognitive functioning at age 70, even in those with early markers of Alzheimer’s disease. If causal, this is likely via multiple pathways, potentially through the preservation of hippocampal volume, as well as via cognitive resilience pathways delaying cognitive manifestations of early markers of Alzheimer’s disease, particularly in women. Our findings warrant further research to shed light on the mechanisms of physical activity as a potential disease-modifying intervention of brain health and cognitive resilience.

Accelerated long-term forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (e.g. minutes) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer’s disease pathology, and how memory selectivity may influence which material is forgotten. We assessed ALF in ‘Insight 46’, a sub-study of the MRC National Survey of Health and Development (a population-based cohort born during one week in 1946) (n=429; 47% female; assessed aged ∼73 years). ALF assessment comprised visual and verbal memory tests: Complex Figure Drawing and the Face-Name Associative Memory Exam (FNAME). ALF scores were calculated as the percentage of material retained after 7 days, relative to 30 minutes. In 306 cognitively-normal participants, we investigated effects on ALF of β-amyloid pathology (quantified using 18F-Florbetapir-PET, classified as positive/negative) and whole-brain and hippocampal atrophy rate (quantified from serial T1-MRI over ∼2.4 years preceding the ALF assessment), as well as interactions between these pathologies. We categorized Complex Figure Drawing items as ‘outline’ or ‘detail’, to test our hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. We also investigated associations between ALF and Subjective Cognitive Decline, measured with the MyCog questionnaire. Complex Figure ‘outline’ items were better retained than ‘detail’ items (mean retention over 7 days = 94% vs 72%). Amyloid-positive participants showed greater forgetting of the Complex Figure outline, compared to amyloid-negatives (90% vs 95%; PPP<0.05). These results provide evidence of associations between some measures of ALF and biomarkers of brain pathologies and subjective cognitive decline in cognitively-normal older adults. On Complex Figure Drawing, ‘outline’ items were better remembered than ‘detail’ items – illustrating the strategic role of memory selectivity – but ‘outline’ items were also relatively more vulnerable to ALF in individuals with amyloid pathology. Overall, our findings suggest that ALF may be a sensitive marker of cognitive changes in preclinical Alzheimer’s disease.

INTRODUCTION: Online assessments are scalable and cost-effective for detecting cognitive changes, especially in elderly cohorts with limited mobility and higher vulnerability to neurological conditions. However, determining the uptake, adherence, and usability of these assessments in older adults, who may have less experience with mobile devices is crucial. METHODS: 1,776 members (aged 77) of the MRC National Survey of Health and Development (NSHD) were invited to complete 13 online cognitive tasks. Adherence was measured through task compliance, while uptake (consent, attempt, completion) was linked to health and sociodemographic factors. Usability was evaluated through qualitative feedback. RESULTS: This study’s consent (56.9%), attempt (80.5%), and completion (88.8%) rates are comparable to supervised NSHD sub-studies. Significant predictors of uptake included education, sex, handedness, cognitive scores, weight, smoking, alcohol consumption, and disease burden. DISCUSSION: With key recommendations followed, online cognitive assessments are feasible, with good adherence, and usability in older adults.

Background Hearing loss has been proposed as a modifiable risk factor for dementia. However, the relationship between hearing, neurodegeneration, and cognitive change, and the extent to which pathological processes such as Alzheimer’s disease and cerebrovascular disease influence these relationships, is unclear. Methods Data from 287 adults born in the same week of 1946 who underwent baseline pure tone audiometry (mean age=70.6 years) and two time point cognitive assessment/multimodal brain imaging (mean interval 2.4 years) were analysed. Hearing impairment at baseline was defined as a pure tone average of greater than 25 decibels in the best hearing ear. Rates of change for whole brain, hippocampal and ventricle volume were estimated from structural MRI using the Boundary Shift Integral. Cognition was assessed using the Pre-clinical Alzheimer’s Cognitive Composite. Regression models were performed to evaluate how baseline hearing impairment associated with subsequent brain atrophy and cognitive decline after adjustment for a range of confounders including baseline β-amyloid deposition and white matter hyperintensity volume. Results 111 out of 287 participants had hearing impairment. Compared with those with preserved hearing, hearing impaired individuals had faster rates of whole brain atrophy, and worse hearing (higher pure tone average) predicted faster rates of hippocampal atrophy. In participants with hearing impairment, faster rates of whole brain atrophy predicted greater cognitive change. All observed relationships were independent of β-amyloid deposition and white matter hyperintensity volume. Conclusions Hearing loss may influence dementia risk via pathways distinct from those typically implicated in Alzheimer’s and cerebrovascular disease in cognitively unimpaired older adults.

Background Consistent patterns of reduced cortical thickness have been identified in early Alzheimer’s disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. Methods Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral β-amyloid (Aβ) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). Results In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aβ status did not. Among Aβ positive participants (n=56), there was some evidence that greater global Aβ standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). Conclusions Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aβ-positivity, robust Aβ-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.