OBJECTIVE: A study was undertaken to examine the relation of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body (LB) pathology to cognition in persons without cognitive impairment. METHODS: Persons without dementia from 2 cohort studies of aging, the Religious Orders Study and the Memory and Aging Project, agreed to annual clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed 5 cognitive domains. For 296 persons without cognitive impairment who died and underwent postmortem assessment, we quantified AD pathology as a global pathology score, and as amyloid load, paired helical filament tau-positive (PHFtau) tangle density, cerebral infarcts, and LB pathology. Linear regression was used to examine the relation of neuropathology to cognitive abilities, controlling for demographics. RESULTS: Nearly all persons had AD pathology with >¾ exhibiting amyloid; 22% had macroscopic and 24% had microscopic infarctions, and 13% had LB pathology. The global measure of AD pathology was related to global cognition (p = 0.008), whereas infarcts and Lewy bodies were not. Amyloid load was related to global cognition (p < 0.05), with only a trend for tangles (p = 0.08). In analyses of cognitive domains, AD pathology (p = 0.006), PHFtau tangles (p = 0.03), and macroscopic infarctions (p = 0.02) were related to episodic memory, with a trend for amyloid load (p = 0.06); AD pathology (p = 0.02) and amyloid load (p = 0.03) were related to working memory. Findings for global cognition and episodic memory were stronger in additional analyses with neocortical amyloid and mesial temporal tangles. INTERPRETATION: AD pathology and macroscopic infarctions are common in older persons without cognitive impairment and are related to episodic and working memory.
OBJECTIVE: A study was undertaken to examine the relation of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body (LB) pathology to cognition in persons without cognitive impairment. METHODS:Persons without dementia from 2 cohort studies of aging, the Religious Orders Study and the Memory and Aging Project, agreed to annual clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed 5 cognitive domains. For 296 persons without cognitive impairment who died and underwent postmortem assessment, we quantified AD pathology as a global pathology score, and as amyloid load, paired helical filament tau-positive (PHFtau) tangle density, cerebral infarcts, and LB pathology. Linear regression was used to examine the relation of neuropathology to cognitive abilities, controlling for demographics. RESULTS: Nearly all persons had AD pathology with >¾ exhibiting amyloid; 22% had macroscopic and 24% had microscopic infarctions, and 13% had LB pathology. The global measure of AD pathology was related to global cognition (p = 0.008), whereas infarcts and Lewy bodies were not. Amyloid load was related to global cognition (p < 0.05), with only a trend for tangles (p = 0.08). In analyses of cognitive domains, AD pathology (p = 0.006), PHFtau tangles (p = 0.03), and macroscopic infarctions (p = 0.02) were related to episodic memory, with a trend for amyloid load (p = 0.06); AD pathology (p = 0.02) and amyloid load (p = 0.03) were related to working memory. Findings for global cognition and episodic memory were stronger in additional analyses with neocortical amyloid and mesial temporal tangles. INTERPRETATION:AD pathology and macroscopic infarctions are common in older persons without cognitive impairment and are related to episodic and working memory.
Authors: Joshua A Sonnen; Eric B Larson; Paul K Crane; Sebastien Haneuse; Ge Li; Gerald D Schellenberg; Suzanne Craft; James B Leverenz; Thomas J Montine Journal: Ann Neurol Date: 2007-10 Impact factor: 10.422
Authors: E C Mormino; J T Kluth; C M Madison; G D Rabinovici; S L Baker; B L Miller; R A Koeppe; C A Mathis; M W Weiner; W J Jagust Journal: Brain Date: 2008-11-28 Impact factor: 13.501
Authors: Joseph L Price; Daniel W McKeel; Virginia D Buckles; Catherine M Roe; Chengjie Xiong; Michael Grundman; Lawrence A Hansen; Ronald C Petersen; Joseph E Parisi; Dennis W Dickson; Charles D Smith; Daron G Davis; Frederick A Schmitt; William R Markesbery; Jeffrey Kaye; Roger Kurlan; Christine Hulette; Brenda F Kurland; Roger Higdon; Walter Kukull; John C Morris Journal: Neurobiol Aging Date: 2009-04-18 Impact factor: 4.673
Authors: Ira Driscoll; Susan M Resnick; Juan C Troncoso; Yang An; Richard O'Brien; Alan B Zonderman Journal: Ann Neurol Date: 2006-12 Impact factor: 10.422
Authors: Clifford R Jack; David S Knopman; William J Jagust; Leslie M Shaw; Paul S Aisen; Michael W Weiner; Ronald C Petersen; John Q Trojanowski Journal: Lancet Neurol Date: 2010-01 Impact factor: 44.182
Authors: Peter T Nelson; Erin L Abner; Frederick A Schmitt; Richard J Kryscio; Gregory A Jicha; Karen Santacruz; Charles D Smith; Ela Patel; William R Markesbery Journal: J Neuropathol Exp Neurol Date: 2009-07 Impact factor: 3.685
Authors: Jason Hassenstab; Sarah E Monsell; Charles Mock; Catherine M Roe; Nigel J Cairns; John C Morris; Walter Kukull Journal: J Neuropathol Exp Neurol Date: 2015-11 Impact factor: 3.685
Authors: Patricia A Boyle; Jingyun Yang; Lei Yu; Sue E Leurgans; Ana W Capuano; Julie A Schneider; Robert S Wilson; David A Bennett Journal: Brain Date: 2017-03-01 Impact factor: 13.501
Authors: Bin He; Sylvia E Perez; Sang H Lee; Stephen D Ginsberg; Michael Malek-Ahmadi; Elliott J Mufson Journal: J Comp Neurol Date: 2020-05-05 Impact factor: 3.215
Authors: Debra A Fleischman; Sue Leurgans; Konstantinos Arfanakis; Zoe Arvanitakis; Lisa L Barnes; Patricia A Boyle; S Duke Han; David A Bennett Journal: Brain Struct Funct Date: 2013-08-17 Impact factor: 3.270
Authors: Jingyun Yang; Lei Yu; Christopher Gaiteri; Gyan P Srivastava; Lori B Chibnik; Sue E Leurgans; Julie A Schneider; Alexander Meissner; Philip L De Jager; David A Bennett Journal: Int J Biochem Cell Biol Date: 2015-05-21 Impact factor: 5.085
Authors: Alexandra M Wennberg; Jennifer L Whitwell; Nirubol Tosakulwong; Stephen D Weigand; Melissa E Murray; Mary M Machulda; Leonard Petrucelli; Michelle M Mielke; Clifford R Jack; David S Knopman; Joseph E Parisi; Ronald C Petersen; Dennis W Dickson; Keith A Josephs Journal: Neurobiol Aging Date: 2019-01-21 Impact factor: 4.673
Authors: Lei Yu; Patricia A Boyle; Eisuke Segawa; Sue Leurgans; Julie A Schneider; Robert S Wilson; David A Bennett Journal: Neuropsychology Date: 2014-12-15 Impact factor: 3.295