Publications

Brown et al. Association of increase in white matter hyperintensity volume with rate of hippocampal atrophy in a population-based study of aging. Neurology. 2025 Sep 9;105(5):e213975.

Canning et al. Associations between life course exposure to ambient air pollution with cognition and later-life brain structure: a population-based study of the 1946 British Birth Cohort. Lancet Healthy Longev. 2025 Jul 16:100724.

Research has shown that air pollution may contribute to dementia and thinking problems in older adults, but it's less clear what happens during midlife. We studied over 1,500 people who took memory and thinking speed tests between ages 43-69. At age 69, participants completed detailed cognitive tests, and some had brain scans. We measured their exposure to different air pollutants (nitrogen dioxide, coarse particles, finer particles, and nitrogen oxides) - accounting for early-life exposure to black smoke and sulfur dioxide. Lastly, we looked at how this may have affected memory and thinking performance and brain structures.

• People exposed to higher levels of nitrogen dioxide and coarse particles had slower thinking speeds (but not worse verbal memory) between ages 43-69
• Higher exposure to all types of pollution was linked to lower scores on cognitive tests at age 69
• Brain scans showed that pollution exposure was associated with enlarged brain ventricles (fluid-filled spaces) and smaller memory centers
• These effects remained even after accounting for earlier pollution exposure, suggesting that reducing air pollution now could help protect older adults' brain health. Future studies will track these brain changes over time.

King-Robson et al. Associations between night/shoft working and late-life brain health. Brain Commun. 2025 Jul 4;7(4):fcaf264.

Cai et al. Online46: Online cognitive assessments in elderly cohorts - The British 1946 birth cohort case study. Alzheimers Dement (Amst). 2025. June 9;17(2):e70098.

As we age, keeping track of our brain health becomes increasingly important—especially for spotting early signs of conditions like Alzheimer’s disease. However, travelling to clinics for regular assessments can be inconvenient for older adults, particularly those with limited mobility. Online tests could be a practical and cost-effective alternative, but how well do they work for this age group, and who is most likely to take part? In this study, we invited 1,776 participants from the British 1946 birth cohort to complete 13 online thinking and memory tests from home. We looked at who took part from start to finish, how well they followed the instructions, and what they thought of the experience. We found that:

• Most participants were willing and able to take part in the tests.
• People with higher education, better previous cognitive scores, and moderate alcohol consumption were more likely to consent to the study.
• Alcohol consumption and body weight were linked to starting a test.
• Whether participants completed the tests was related to sex, smoking habits, and the presence of health conditions.
• Participants’ feedback also highlighted some challenges in the testing process, leading to recommendations for making future online tests easier and more engaging.

Fatih et al. Sex differences between mid-life glycaemic traits and brain volume at age 70: a population-based study. Eur J Endocrinol. 2025 Apr 30; 192(5):K44-K49.

Lu et al. Associations between accelerated forgetting, amyloid deposition and brain atrophy in older adults. Brain. 2025 Apr 3;148(4):1302-1315.

Our researchers studied "accelerated long-term forgetting" (ALF), where people remember things normally short-term but forget them unusually quickly long-term. They wanted to see if this could signal early Alzheimer’s Disease. The study involved 73-year-olds from the British 1946 birth cohort. Participants completed two memory tests: drawing a complex figure and recalling faces with names and occupations. They were tested after 30 minutes and again after 7 days.

• Participants remembered the figure’s basic outline better (94%) than its details (72%).
• Those with higher amyloid (a protein linked to Alzheimer’s) had more trouble remembering the outline.
• Elevated amyloid levels were also linked to brain shrinkage and faster forgetting.
• Faster forgetting of face-name pairs was associated with more shrinkage in the hippocampus, a brain region crucial for memory.
• Those with memory concerns in daily life also showed more forgetting on the drawing test.
• This study suggests faster forgetting over time is linked to brain changes and self-reported memory concerns, even in people without a formal diagnosis of memory problems. The pattern of accelerated forgetting could help identify those at risk for Alzheimer’s before obvious symptoms emerge.

Giovane et al. Remote cognitive tests predict neurodegenerative biomarkers in the Insight 46 cohort. Alzheimers Dementia. 2025 Feb;21(2):e14572.

Alzheimer’s disease can begin silently in the brain many years before any noticeable memory or thinking problems appear. Researchers want to catch these early changes because that’s when treatments may help the most. One way to do this is through simple “thinking tests” that people can complete from home using any electronic device. In this study, 255 members of the Insight 46 cohort (all born within the same week of 1946) took 13 online memory and thinking tests from home. By comparing their test results to detailed brain scans, we found that:

• Slower speed and reduced accuracy on memory tasks were associated with protein build-up in the brain linked to Alzheimer’s disease.
• Better performance on tasks measuring memory and spatial abilities corresponded to slower brain shrinkage over time.
• Scores on the online tests closely matched those from standard paper-and-pencil tests.
• These findings suggest that at-home computerised testing can help identify early memory problems associated with Alzheimer’s disease, offering a way to flag individuals who might benefit from early treatment or closer monitoring.

James et al. The relationship between leisure time physical activity patterns, Alzheimer's disease markers and cognition. Brain communications. 2025 Jan 31;7(1):fcae431.

Dijsselhof et al. Associations of life-course cardiovascular risk factors with late-life cerebral haemodynamics. J Cereb Blood Flow Metab. 2025 Apr;45(4):765-778. Epub 2024 Nov 17. 

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Subramaniapillai et al. Sex-Dependent Effects of Cardiometabolic Health and APOE4 on Brain Age: A Longitudinal Cohort Study. Neurology. 2024 Sep 24;103(6):e209744. Epub 2024 Aug 22.

Parker et al. Peripheral hearing loss at age 70 predicts brain atrophy and associated cognitive change. J Neurol Neurosurg Psychiatry. 2024 Aug 16;95(9):829-832.

While hearing loss has been known to raise the risk of dementia, it's still uncertain how hearing issues contribute to brain changes and memory decline. It is also unclear if this link is tied to typical dementia causes or blood vessel problems in the brain. Our researchers studied 287 people all born in the same week of 1946. They tested everyone’s hearing, took brain scans at two different time points (2.4 years apart), gave memory and thinking tests, and finally, looked for signs of Alzheimer’s disease and blood vessel problems in the brain.
111 out of the 287 participants had hearing problems

• People with hearing problems showed faster brain shrinkage than those with normal hearing
• The worse someone’s hearing was, the faster the hippocampus (a brain region crucial for memory) shrank
• In people with hearing problems, faster brain shrinkage was linked to bigger declines in memory and thinking
• These relationships, however, were not explained by signs of Alzheimer’s disease or blood vessel problems in the brain
• These findings suggest that hearing loss may increase dementia risk through different pathways than those usually linked to Alzheimer's Disease or blood vessel problems in the brain.

Keuss et al. Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with β -amyloid status in cognitively normal adults at age 70. J Neurol Neurosurg Psychiatry. 2024 Jul 15;95(8):748-752.

Scientists know that in early Alzheimer’s disease, certain areas of the brain’s outer layer (cortex) become thinner. However, we aren’t sure what exactly causes these specific areas to thin more quickly. Our researchers studied 337 adults from the 1946 British birth cohort and used brain scans to look at levels of amyloid (a protein which builds up in Alzheimer’s disease), white matter damage (a marker of blood vessel health) and changes in cortex thickness.

• Greater white matter damage was associated with faster rates of cortex thinning in brain areas typically affected in Alzheimer’s Disease.
• Having significant amyloid in the brain was not related to rates of cortex thinning.
• This research highlights that poorer blood vessel health may be related to faster cortical thinning in areas of the brain typically affected in Alzheimer’s disease. Future research plans include continuing to follow members of this study to see how these relationships might change as they get older and closer to the age dementia typically develops.

Green et al. Common infections and neuroimaging markers of dementia in three UK cohort studies. Alzheimers Dement. 2024 Mar;20(3):2128-2142. Epub 2024 Jan 22. 

Murray-Smith et al. Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3. BMC Neurol. 2024 Jan 23;24(1):40.

Participants in this cohort are now at an important age for studying healthy ageing and brain changes. By combining detailed information about their entire lives with new brain scans and health measurements, this research could help us better understand what influences healthy ageing and dementia risk. Researchers are also planning to add new elements like sleep studies and online memory tests.
While we know ageing is the biggest risk factor for dementia, we still aren’t sure what specific factors through a person's life might affect their risk of memory problems later in life. The Insight46 study aims to help fill in these gaps by following a group of people who have been studied since their birth in 1946. This research paper outlines this study’s protocol. This study has 3 phases:

• Phase 1 (2015-2018): They studied 502 people, collecting detailed information about brain health, thinking abilities, physical health, heart health, and sensory functions.
• Phase 2 (2018-2021): 442 people returned for follow-up visits, though some had to participate remotely due to COVID-19.
• Phase 3 (2021-ongoing): We are aiming to follow 250 people who participated in both earlier phases and add 500 new participants who haven’t participated yet.

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James et al. Adulthood cognitive trajectories over 26 years and brain health at age 70: Findings from the 1946 British Birth Cohort. Neurobiol Aging. 2023 Feb122:22-32. Epub 2022 Oct 18.

Green et al. Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease. Alzheimer’s Res Ther. 2023 Feb 22;15(1):38.

James et al. Timing of physical activity across adulthood on later-life cognition: 30 years follow-up in the 1946 British birth cohort. J Neurol Neurosurg Psychiatry. 2023 May;94(5):349-356.

Coath et al. Operationalizing the centiloid scale for [18F]florbetapir PET studies on PET/MRI. Alzheimers Dement (Amst). 2023 May 16;15(2):e12434.

Needham et al. A comprehensive assessment of age at menopause with well-characterized cognition at 70 years: A population-based British birth cohort. Maturitas. 2023 Apr; 1701:31-38.

James et al. Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds: A population-based study. Brain Commun. 2023 Aug 18;5(5):fcad225.

Bollack et al. Evaluation of novel data-driven metrics of amyloid β depoisition for longitudinal PET studies. Neuroimage. 2023 Oct 15:280:120313.

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Keuss et al. Associations of amyloid-β and vascular burden with rates of neurodegeneration in cognitively normal members of the 1946 British birth cohort. Neurology. 2022 July 12;99(2):e129-e141.

Fatih et al. Sex-related differences in whole brain volumes at age 70 in association with hyperglycemia during adult life. Neurobiol Aging. 2022 Apr;112:161-169.

Sliz et al. Circulating metabolome and white matter hyperintensities in women and men. Circulation. 2022 Apr 5;145(14):1040-1052.

Dercon et al. Grip strength from midlife as an indicator of later-life brain health and cognition: evidence from a British birth cohort. BMC Geriatr. 2022 Aug 21;21(1):475.

Mason et al. Association between carotid atherosclerosis and brain activation patterns during the Stroop task in older adults: an fNIRS investigation. Neuroimage. 2022 Aug 15;257:119302.

Wagen et al. Life course, genetic and neuropathological associations with brain age: a study of the British 1946 Birth Cohort. Lancet Healthy Longev. 2022 Sep;3(9):e6-7-e616.

Richards et al. Straight and Divergent Pathways to Cognitive State: Seven Decades of Follow-Up in the British 1946 Birth Cohort. J Alzheimers Dis. 2022;89(2):659-667.

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Keshavan et al. Population-based blood screening for pre-clinical Alzheimer’s disease in a British birth cohort at age 70. Brain. 2021 Mar 3;144(2):434-449.

Lu et al. Visuomotor integration deficits are common to familial and sporadic preclinical Alzheimer’s disease. Brain Commun. 2021 Jan 25;3(1):fcab003.

James et al. A population-based study of head injury, cognitive function and pathological markers. Ann Clin Transl Neurol. 2021 Apr;8(4):842-856.

Keshavan et al. Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays. Alzheimers Dement (Amst). 2021 Feb 6;13(1):e12131. 

Lane et al. Investigating the relationship between BMI across adulthood and late life brain pathologies. Alzheimers Res Ther. 2021 Apr 30;13(1):91.

Belloy et al. KL*VS heterozygosity reduces brain amyloid in asymptomatic at-risk APOE*4 carriers. Neurobiol Aging. 2021 May:101:123-129.

Pavisic et al. Subjective cognitive complaints at age 70: Associations with amyloid and mental health. J Neurol Neurosurg Psychiatry. 2021 Nov;92(11):1215-1221.

Dercon et al. Grip strength from midlife as an indicator of later-life brain health and cognition: evidence from a British birth cohort. BMC Geriat. 2021 Sep 29;21(1):518.

Lu et al. Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory. Nat Aging. 2021 Nov;1(11):1002-1009.

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Lu et al. Increased variability in reaction time is associated with amyloid beta pathology at age 70. Alzheimers Dement. 2020 Aug 10;12(1):e12076. 

Buchanan et al. Olfactory testing does not predict β‑amyloid, MRI measures of neurodegeneration or vascular pathology in the British 1946 birth cohort. J Neurol. 2020 June 24;267(11):3329-3336.

Tektonidis et al. Diet quality in late midlife is associated with faster walking speed in later life in women, but not men: findings from a prospective British birth cohort. Br J Nutr. 2020 Apr 28;123(8):913-921. Epub 2019 Dec 16.

Mason et al. Study Protocol - Insight 46 Cardiovascular: A sub-study of the MRC National Survey of Health and Development. Artery Res. 2020 Sep;26(3):170-179. Epub 2020 Apr 24.

Parker et al. Amyloid B influences the relationship between cortical thickness and vascular load. Alzheimers Dement. 2020 Apr 17;12(1):e12022. 

Parker et al. Pure tone audiometry and cerebral pathology in healthy older adults. J Neurol Neurosurg Psychiatry. 2020 Feb;91(2):172-176. Epub 2019 Nov 7.

Lane et al. Associations between vascular risk across adulthood and brain pathology in late life - evidence from a British birth cohort. JAMA Neurol. 2020 Feb 1;77(2):175-183.

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Keuss et al. Incidental findings on brain imaging and blood tests: results from the first phase of Insight 46, a prospective observational substudy of the 1946 British birth cohort. BMJ Open. 2019 Jul;9(7):e029502.

Parker et al. Hippocampal subfield volumes and pre-clinical Alzheimer’s disease in 408 cognitively normal adults born in 1946. PLoS One. 2019 Oct 17;14(10):e0224030.

Lane et al. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. Lancet Neurol. 2019 Oct;18(10):942-952. Epub 2019 Aug 20.

Lu et al. Cognition at age 70: Life course predictors and associations with brain pathologies. Neurology. 2019 Dec 3;93(23):e2144-e2156. Epub 2019 Oct 30.

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James et al. Using a birth cohort to study brain health and preclinical dementia: recruitment and participation rates in Insight 46. BMC Res Notes. 2018 Dec 13;11(1):885.

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Lane, Parker, et al. Study protocol: Insight 46 – a neuroscience sub-study of the MRC National Survey of Health and Development. BMC Neurol. 2017 Apr 18;17(1):75.

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