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Introduction/Aims: Sporadic inclusion body myositis (IBM) is a degenerative and inflammatory acquired myopathy characterized by muscle deposition of various proteins typically associated with Alzheimer disease and other neurodegenerative diseases. Although cognitive impairment is not noted as a clinical feature of IBM, evidence is lacking. In this study we investigated whether cognitive performance of patients with IBM differs from population norms, focusing on cognitive domains affected in early Alzheimer disease (memory, executive function), and to test whether disease duration and the level of disability of IBM are associated with cognitive function. Methods: Twenty‐four patients with IBM (mean [standard deviation]: age, 62.0 [7.2] years; disease duration, 9.6 [4.8] years) were assessed cross‐sectionally on neuropsychological tests covering multiple cognitive domains, including the Preclinical Alzheimer Cognitive Composite (PACC). Performance was compared with published normative data adjusted for age, sex, and education (National Alzheimer's Coordinating Center; N = 3268). Associations were examined between PACC score, disease duration, and level of disability (assessed using the IBM Functional Rating Scale [IBMFRS]). Results: Across all cognitive tests, group performance was within ±1 standard deviation of the normative mean. There was no evidence of associations between PACC score and either disease duration (ρ = −0.04, P =.87) or IBMFRS total score (ρ = 0.14, P =.52). Discussion: Memory and executive function in patients with IBM did not differ from normative data, and we observed no evidence of associations between the cognitive composite and disease duration or level of disability. This addresses a question frequently asked by patients and will be of value for clinicians and patients alike. [ABSTRACT FROM AUTHOR]

Background: Understanding the earliest manifestations of Alzheimer's disease (AD) is key to realising disease-modifying treatments. Advances in neuroimaging and fluid biomarkers have improved our ability to identify AD pathology in vivo. The critical next step is improved detection and staging of early cognitive change. We studied an asymptomatic familial Alzheimer's disease (FAD) cohort to characterise preclinical cognitive change. Methods: Data included 35 asymptomatic participants at 50% risk of carrying a pathogenic FAD mutation. Participants completed a multi-domain neuropsychology battery. After accounting for sex, age and education, we used event-based modelling to estimate the sequence of cognitive decline in presymptomatic FAD, and uncertainty in the sequence. We assigned individuals to their most likely model stage of cumulative cognitive decline, given their data. Linear regression of estimated years to symptom onset against model stage was used to estimate the timing of preclinical cognitive decline. Results: Cognitive change in mutation carriers was first detected in measures of accelerated long-term forgetting, up to 10 years before estimated symptom onset. Measures of subjective cognitive decline also revealed early abnormalities. Our data-driven model demonstrated subtle cognitive impairment across multiple cognitive domains in clinically normal individuals on the AD continuum. Conclusions: Data-driven modelling of neuropsychological test scores has potential to differentiate cognitive decline from cognitive stability and to estimate a fine-grained sequence of decline across cognitive domains and functions, in the preclinical phase of Alzheimer's disease. This can improve the design of future presymptomatic trials by informing enrichment strategies and guiding the selection of outcome measures. [ABSTRACT FROM AUTHOR]

While the associations of mid-life cardiovascular risk factors with late-life white matter lesions (WMH) and cognitive decline have been established, the role of cerebral haemodynamics is unclear. We investigated the relation of late-life (69–71 years) arterial spin labelling (ASL) MRI-derived cerebral blood flow (CBF) with life-course cardiovascular risk factors (36–71 years) and late-life white matter hyperintensity (WMH) load in 282 cognitively healthy participants (52.8% female). Late-life (69–71 years) high systolic (B = −0.15) and diastolic (B = −0.25) blood pressure, and mean arterial pressure (B = −0.25) were associated with low grey matter (GM) CBF (p < 0.03), and white matter CBF (B = −0.25; B = −0.15; B = −0.13, p < 0.03, respectively). The association between systolic blood pressure and GM CBF differed between sexes (male/female B = −0.15/0.02, p = 0.04). No associations were found with early- or mid-life cardiovascular risk factors. Furthermore, WMHs were associated with cerebral haemodynamics but not cardiovascular risk factors. These findings suggest that cerebral blood flow autoregulation is able to maintain stable global cerebral haemodynamics until later in life. Future studies are encouraged to investigate why cardiovascular risk factors have differential effects on haemodynamics and WMH, and their implications for cognitive decline. [ABSTRACT FROM AUTHOR]

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%; P<0.01). There were interactions between amyloid pathology and cerebral atrophy, such that whole-brain and hippocampal atrophy predicted greater ALF on Complex Figure Drawing among amyloid-positives only (e.g. 1.9 percentage-points lower retention per ml/year of whole-brain atrophy [95% confidence intervals 0.5, 3.7]; P<0.05). Greater ALF on FNAME was associated with increased rate of hippocampal atrophy. ALF on Complex Figure Drawing also correlated with subjective cognitive decline (-0.45 percentage-points per MyCog point [-0.85, -0.05], P<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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: The BRAIN Study was established to assess the associations between self-reported concussions and cognitive function among retired rugby players., Methods: Former elite-level male rugby union players (50+ years) in England were recruited. Exposure to rugby-related concussion was collected using the BRAIN-Q tool. The primary outcome measure was the Preclinical Alzheimer Cognitive Composite (PACC). Linear regressions were conducted for the association between concussion and PACC score, adjusting for confounders., Results: A total of 146 participants were recruited. The mean (standard deviation) length of playing career was 15.8 (5.4) years. A total of 79.5% reported rugby-related concussion(s). No association was found between concussion and PACC (β -0.03 [95% confidence interval (CI): -1.31, 0.26]). However, participants aged 80+ years reporting 3+ concussions had worse cognitive function than those without concussion (β -1.04 [95% CI: -1.62, -0.47])., Conclusions: Overall there was no association between concussion and cognitive function; however, a significant interaction with age revealed an association in older participants., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We investigated whether life-course factors and neuroimaging biomarkers of Alzheimer's disease pathology predict reaction time (RT) performance in older adults., Methods: Insight 46 study participants, all born in the same week in 1946 (n = 501; ages at assessment = 69 to 71 years), completed a 2-choice RT task and amyloid beta (Aβ) positron emission tomography and MR imaging. We tested for associations between task outcomes (RT; error rate; intra-individual variability in RT) and life-course predictors including childhood cognitive ability and education. In a subsample of 406 cognitively normal participants, we investigated associations between task outcomes and biomarkers including Aβ-positivity., Results: Cognitively normal Aβ-positive participants had 10% more variable RTs than Aβ-negative participants, despite having similar mean RTs. Childhood cognitive ability and education independently predicted task performance., Discussion: This study provides novel evidence that Aβ pathology is associated with poorer consistency of RT in cognitively normal older adults, at an age when dementia prevalence is still very low., Competing Interests: Kirsty Lu reports no disclosures. Jennifer M. Nicholas reports no disclosures. Sarah‐Naomi James reports no disclosures. Thomas D. Parker is supported by a Wellcome Trust Clinical Research Fellowship (200109/Z/15/Z). Christopher A. Lane reports no disclosures. Ashvini Keshavan is supported by a Clinical Research Fellowship funded by the Wolfson Foundation. Sarah E. Keuss reports no disclosures. Sarah M. Buchanan reports no disclosures. Heidi Murray‐Smith reports no disclosures. David M. Cash is supported by an Alzheimer's Society Project Grant (AS‐PG‐205). Carole H. Sudre is supported by an Alzheimer's Society Junior Fellowship (AS‐JF‐17‐011). Ian B. Malone reports no disclosures. William Coath reports no disclosures. Andrew Wong reports no disclosures. Susie M.D. Henley reports no disclosures. Nick C. Fox is supported by the UCL/UCLH NIHR Biomedical Research Centre and the UK Dementia Research Institute at UCL. Marcus Richards reports no disclosures. Jonathan M. Schott is supported by the UCL/UCLH NIHR Biomedical Research Centre, UCL Hospitals Biomedical Research Centre, and Leonard Wolfson Experimental Neurology Centre and acknowledges the EPSRC (EP/J020990/1) and European Union's Horizon 2020 research and innovation programme (Grant 666992). Sebastian J. Crutch is supported by an Alzheimer's Research UK Senior Research Fellowship (ARUK‐SRF2013‐8)., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.)

Introduction: Cortical thickness has been proposed as a biomarker of Alzheimer's disease (AD)- related neurodegeneration, but the nature of its relationship with amyloid beta (Aβ) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear., Methods: We investigated the influences of Aβ status (negative/positive) and WMHV on cortical thickness in 408 cognitively normal adults aged 69.2 to 71.9 years who underwent 18 F-Florbetapir positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Two previously defined Alzheimer's disease (AD) cortical signature regions and the major cortical lobes were selected as regions of interest (ROIs) for cortical thickness., Results: Higher WMHV, but not Aβ status, predicted lower cortical thickness across all participants, in all ROIs. Conversely, when Aβ-positive participants were considered alone, higher WMHV predicted higher cortical thickness in a temporal AD-signature region., Discussion: WMHV may differentially influence cortical thickness depending on the presence or absence of Aβ, potentially reflecting different pathological mechanisms., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.)