Delta beta-thalassaemia in two Turkish families.

Abstract

<h3>Objective:</h3> To examine the impact of 3 pathologic groups; ‘pure’ LATE-NC, ‘pure’ ADNC, and mixed ADNC with LATE-NC, on late-life cognitive decline. <h3>Methods:</h3> Data came from 1,356 community-based older persons, who completed detailed annual cognitive testing and systematic neuropathological examination at autopsy to identify LATE-NC, ADNC, and other age-related pathologies. Persons were categorized into <b>(0)</b> a group without a pathologic diagnosis of LATE or ADNC (n=378), <b>(1)</b> LATE-NC without ADNC (n=91), <b>(2)</b> ADNC without LATE-NC (n=535), and <b>(3</b>) mixed ADNC with LATE-NC (n=352). We employed mixed-effect models to examine the group associations with rate of decline in global cognition and 5 cognitive domains, and then examined whether age modified associations. <h3>Results:</h3> Compared to those without LATE-NC or ADNC, ‘pure’ LATE-NC had a faster decline in global cognition (<i>p</i>=0.025) and episodic memory (<i>p</i>=0.002); however, compared to persons with ‘pure’ ADNC, those with ‘pure’ LATE-NC showed a slower decline. Those with mixed ADNC with LATE-NC showed the fastest decline, compared to those with either pathology alone. Persons aged 90 years and above with mixed ADNC with LATE-NC had slower cognitive decline compared to those 89 years and below. <h3>Conclusion:</h3> Persons with ‘pure’ LATE-NC follow a slower trajectory compared to those with ‘pure’ ADNC. Those with mixed LATE/ADNC have a steeper decline then either pathology alone. In addition, age may modify the effect of pathology on cognitive decline. These findings have important implications for the development of biomarkers and prognosis for late-life cognitive decline. <h3>Classification of Evidence:</h3> This study provides Class I evidence that LATE-NC and AD pathological changes are associated with different trajectories of late-life cognitive decline.