{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:33:34Z","timestamp":1780061614716,"version":"3.54.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,29]],"date-time":"2020-03-29T00:00:00Z","timestamp":1585440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Memory is known to be the most common first symptom in Alzheimer\u2019s disease (AD). Assessing non\u2010memory cognitive symptom development in AD is important for understanding disease progression and the potential identification of treatment\u2010responsive subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from the National Alzheimer\u2019s Coordinating Center were examined. Logistic regression models were fitted evaluating the development of judgement, language, visuospatial and attention symptoms at first and second visits to Alzheimer\u2019s Disease Centers. Predictors were age and prior symptoms, adjusting for symptom length and sex. The models were then refitted assessing apolipoprotein E \u03b54 (APOE\u2010\u03b54) effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Each decade reduction in presentation age increased the odds of language, visuospatial and attention symptom development at both visits by 8%\u201318% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05, all tests), and judgement symptoms at the second visit by 13% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Prior symptoms were not equally predictive of symptom development. For example, having first predominant language symptoms carried the lowest risk of developing other first\u2010visit symptoms and having memory symptoms was a stronger predictor of developing judgement than other symptoms. The APOE\u2010\u03b54 gene showed little impact on symptom development when included as a predictor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings provide support for the concept that younger\u2010onset AD is associated with the progressive development of more non\u2010memory symptoms beyond the first time point. Associations between symptoms were evident, which may reflect that pathology can remain isolated in a network for some time. APOE\u2010\u03b54 status had little influence on cognitive symptom development which may indicate that the effect it has occurs very early in the disease course.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.14185","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T15:54:19Z","timestamp":1582214059000},"page":"995-1002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Non\u2010memory cognitive symptom development in Alzheimer's disease"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-8671","authenticated-orcid":false,"given":"A.","family":"Blenkinsop","sequence":"first","affiliation":[{"name":"Institute of Clinical Trials and Methodology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Department of Neurology Alzheimer Center Neuroscience Campus Amsterdam VU University Medical Center Amsterdam The Netherlands"},{"name":"Department of Epidemiology and Biostatistics Neuroscience Campus Amsterdam VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Wolk","sequence":"additional","affiliation":[{"name":"Department of Neurology Penn Memory Center University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease Dementia Research Centre UCL Institute of Neurology National Hospital for Neurology and Neurosurgery London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Howard","sequence":"additional","affiliation":[{"name":"Division of Psychiatry University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Frost","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics London School of Hygiene and Tropical Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease Dementia Research Centre UCL Institute of Neurology National Hospital for Neurology and Neurosurgery London 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