BACKGROUND: Subjective memory complaints are common in aged persons, indicating an increased, but incompletely understood, risk for dementia. OBJECTIVE: To compare cognitive trajectories and autopsy results of individuals with subjective complaints after stratifying by whether a subsequent clinical dementia occurred. DESIGN: Observational study. SETTING: University of Kentucky cohort with yearly longitudinal assessments and eventual autopsies. PARTICIPANTS: Among 516 patients who were cognitively intact and depression-free at enrollment, 296 declared a memory complaint during follow-up. Among those who came to autopsy, 118 died but never developed dementia, while 36 died following dementia diagnosis. MEASUREMENTS: Cognitive domain trajectories were compared using linear mixed models adjusted for age, gender, years of education and APOE status. Neuropathological findings were compared cross-sectionally after adjustment for age at death. RESULTS: While the groups had comparable cognitive test scores at enrollment and the time of the first declaration of a complaint, the group with subsequent dementia development had steeper slopes of decline in episodic memory and naming but not fluency or sequencing. Autopsies showed the dementia group had more severe Alzheimer pathology and a higher proportion of subjects with hippocampal sclerosis of aging and arteriolosclerosis, whereas the non-demented group had a higher proportion expressing primary age related tauopathy (PART). CONCLUSIONS: While memory complaints are common among the elderly, not all individuals progress to dementia. This study indicates that biomarkers are needed to predict whether a complaint will lead to dementia if this is used as enrollment criteria in future clinical trials.
BACKGROUND: Subjective memory complaints are common in aged persons, indicating an increased, but incompletely understood, risk for dementia. OBJECTIVE: To compare cognitive trajectories and autopsy results of individuals with subjective complaints after stratifying by whether a subsequent clinical dementia occurred. DESIGN: Observational study. SETTING: University of Kentucky cohort with yearly longitudinal assessments and eventual autopsies. PARTICIPANTS: Among 516 patients who were cognitively intact and depression-free at enrollment, 296 declared a memory complaint during follow-up. Among those who came to autopsy, 118 died but never developed dementia, while 36 died following dementia diagnosis. MEASUREMENTS: Cognitive domain trajectories were compared using linear mixed models adjusted for age, gender, years of education and APOE status. Neuropathological findings were compared cross-sectionally after adjustment for age at death. RESULTS: While the groups had comparable cognitive test scores at enrollment and the time of the first declaration of a complaint, the group with subsequent dementia development had steeper slopes of decline in episodic memory and naming but not fluency or sequencing. Autopsies showed the dementia group had more severe Alzheimer pathology and a higher proportion of subjects with hippocampal sclerosis of aging and arteriolosclerosis, whereas the non-demented group had a higher proportion expressing primary age related tauopathy (PART). CONCLUSIONS: While memory complaints are common among the elderly, not all individuals progress to dementia. This study indicates that biomarkers are needed to predict whether a complaint will lead to dementia if this is used as enrollment criteria in future clinical trials.
Authors: Frederick A Schmitt; Peter T Nelson; Erin Abner; Stephen Scheff; Gregory A Jicha; Charles Smith; Gregory Cooper; Marta Mendiondo; Deborah D Danner; Linda J Van Eldik; Allison Caban-Holt; Mark A Lovell; Richard J Kryscio Journal: Curr Alzheimer Res Date: 2012-07 Impact factor: 3.498
Authors: Frank Jessen; Birgitt Wiese; Cadja Bachmann; Sandra Eifflaender-Gorfer; Franziska Haller; Heike Kölsch; Tobias Luck; Edelgard Mösch; Hendrik van den Bussche; Michael Wagner; Anja Wollny; Thomas Zimmermann; Michael Pentzek; Steffi G Riedel-Heller; Heinz-Peter Romberg; Siegfried Weyerer; Hanna Kaduszkiewicz; Wolfgang Maier; Horst Bickel Journal: Arch Gen Psychiatry Date: 2010-04
Authors: Li Wang; Gerald van Belle; Paul K Crane; Walter A Kukull; James D Bowen; Wayne C McCormick; Eric B Larson Journal: J Am Geriatr Soc Date: 2004-12 Impact factor: 5.562
Authors: Katherine A Gifford; Dandan Liu; Zengqi Lu; Yorghos Tripodis; Nicole G Cantwell; Joseph Palmisano; Neil Kowall; Angela L Jefferson Journal: Alzheimers Dement Date: 2013-07-16 Impact factor: 21.566
Authors: David S Knopman; Samantha Budd Haeberlein; Maria C Carrillo; James A Hendrix; Geoff Kerchner; Richard Margolin; Paul Maruff; David S Miller; Gary Tong; Maria B Tome; Melissa E Murray; Peter T Nelson; Mary Sano; Niklas Mattsson; David L Sultzer; Thomas J Montine; Clifford R Jack; Hartmuth Kolb; Ronald C Petersen; Prashanthi Vemuri; Megan Zoschg Canniere; Julie A Schneider; Susan M Resnick; Gary Romano; Argonde Corien van Harten; David A Wolk; Lisa J Bain; Eric Siemers Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Lilah M Besser; Charles Mock; Merilee A Teylan; Jason Hassenstab; Walter A Kukull; John F Crary Journal: J Neuropathol Exp Neurol Date: 2019-03-01 Impact factor: 3.685
Authors: Lilah M Besser; Walter A Kukull; Merilee A Teylan; Eileen H Bigio; Nigel J Cairns; Julia K Kofler; Thomas J Montine; Julie A Schneider; Peter T Nelson Journal: J Neuropathol Exp Neurol Date: 2018-08-01 Impact factor: 3.685
Authors: Peter T Nelson; Erin L Abner; Ela Patel; Sonya Anderson; Donna M Wilcock; Richard J Kryscio; Linda J Van Eldik; Gregory A Jicha; Zsombor Gal; Ruth S Nelson; Bela G Nelson; Jozsef Gal; Md Tofial Azam; David W Fardo; Matthew D Cykowski Journal: J Neuropathol Exp Neurol Date: 2018-01-01 Impact factor: 3.685
Authors: Vanessa D Smith; Adam D Bachstetter; Eseosa Ighodaro; Kelly Roberts; Erin L Abner; David W Fardo; Peter T Nelson Journal: Brain Pathol Date: 2017-03-24 Impact factor: 6.508
Authors: Keith A Josephs; Melissa E Murray; Nirubol Tosakulwong; Jennifer L Whitwell; David S Knopman; Mary M Machulda; Stephen D Weigand; Bradley F Boeve; Kejal Kantarci; Leonard Petrucelli; Val J Lowe; Clifford R Jack; Ronald C Petersen; Joseph E Parisi; Dennis W Dickson Journal: Acta Neuropathol Date: 2017-02-03 Impact factor: 17.088
Authors: Jacob W Vogel; Monika Varga Doležalová; Renaud La Joie; Shawn M Marks; Henry D Schwimmer; Susan M Landau; William J Jagust Journal: Neurology Date: 2017-10-06 Impact factor: 9.910