@article{2f857e7dfe174d238e74faf4dc155ad8,
title = "Straight and Divergent Pathways to Cognitive State: Seven Decades of Follow-Up in the British 1946 Birth Cohort",
abstract = "BACKGROUND: Using the British 1946 birth cohort we previously estimated life course paths to the Addenbrooke's Cognitive Examination (ACE-III). OBJECTIVE: We now compared those whose ACE-III scores were expected, worse and better than predicted from the path model on a range of independent variables including clinical ratings of cognitive impairment and neuroimaging measures. METHODS: Predicted ACE-III scores were categorized into three groups: those with Expected (between -1.5 and 1.5 standard deviation; SD); Worse (< -1.5 SD); and Better (>1.5 SD) scores. Differences in the independent variables were then tested between these three groups. RESULTS: Compared with the Expected group, those in the Worse group showed independent evidence of progressive cognitive impairment: faster memory decline, more self-reported memory difficulties, more functional difficulties, greater likelihood of being independently rated by experienced specialist clinicians as having a progressive cognitive impairment, and a cortical thinning pattern suggestive of preclinical Alzheimer's disease. Those in the Better group showed slower verbal memory decline and absence of independently rated progressive cognitive impairment compared to the Expected group, but no differences in any of the other independent variables including the neuroimaging variables. CONCLUSION: The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective.",
keywords = "Addenbrooke{\textquoteright}s Cognitive Examination-III, birth cohort, cognitive state, life course, residuals",
author = "Marcus Richards and James, {Sarah N.} and Kirsty Lu and Gill Livingston and Schott, {Jonathan M.} and Lane, {Christopher A.} and Josephine Barnes and Parker, {Thomas D.} and Sudre, {Carole H.} and Cash, {David M.} and William Coath and Nicholas Fox and Davis, {Daniel H. J.}",
note = "Funding Information: We thank MRC National Survey of Health and Development (NSHD) individuals for their lifelong participation and past and present members of the NSHD study team who helped to collect the data. The UK Medical Research Council provides core funding for the NSHD and supports MR and SNJ by grants MC_UU_12019/1 (Enhancing NSHD) and /3 (Mental Ageing). SNJ is additionally funded by Alzheimer{\textquoteright}s Research UK (ARUK-PG2014-1946, ARUK- PG2017-1946). Insight 46 is principally funded by grants from Alzheimer{\textquoteright}s Research UK (ARUK-PG2014-1946, ARUK-PG2017-1946), the Medical Research Council Dementias Platform UK (CSUB19166), and the Wolfson Foundation (PR/ylr/ 18575). Florbetapir amyloid tracer is kindly provided by Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly). JS acknowledges the support of the National Institute for Health Research University College London Hospitals Biomedical Research Centre and the Alzheimer{\textquoteright}s Association (SG-666374). GL is supported by University College London Hospitals{\textquoteright} National Institute for Health Research (NIHR) Biomedical Research Centre, the National Institute for Health Research ARC North Thames and as an NIHR Senior Investigator. CS is supported by an Alzheimer{\textquoteright}s Society Junior Fellowship (AS-JF-17-011). TP is funded by a Wellcome Trust Fellowship (200109/Z/15/Z). DD is funded through a Wellcome Intermediate Clinical Fellowship (WT107467). The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. The funders had no role in the study or the decision to submit this paper for publication. Publisher Copyright: {\textcopyright} 2022-IOS Press. All rights reserved.",
year = "2022",
month = aug,
day = "9",
doi = "https://doi.org/10.3233/JAD-220296",
language = "English",
volume = "89",
pages = "659--667",
journal = "Journal of Alzheimer's disease : JAD",
issn = "1387-2877",
publisher = "IOS Press",
number = "2",
}