Modeling the Association between 43 Different Clinical and Pathological Variables and the Severity of Cognitive Impairment in a Large Autopsy Cohort of Elderly Persons

被引:183
作者
Nelson, Peter T. [1 ]
Abner, Erin L.
Schmitt, Frederick A.
Kryscio, Richard J.
Jicha, Gregory A.
Smith, Charles D.
Davis, Daron G.
Poduska, John W.
Patel, Ela
Mendiondo, Marta S.
Markesbery, William R.
机构
[1] Univ Kentucky, Dept Pathol, Div Neuropathol, Lexington, KY 40536 USA
关键词
ApoE; cognition; human; stroke; DLB; hippocampal sclerosis; MENTAL-STATE-EXAMINATION; FRONTOTEMPORAL LOBAR DEGENERATION; HIPPOCAMPAL SCLEROSIS DEMENTIA; ALZHEIMER-DISEASE PATHOLOGY; ARGYROPHILIC GRAIN DISEASE; NEUROFIBRILLARY TANGLES; NEURITIC PLAQUES; RISK-FACTORS; LATE-LIFE; TDP-43; IMMUNOREACTIVITY;
D O I
10.1111/j.1750-3639.2008.00244.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We evaluated the association between mini-mental status examination (MMSE) scores proximal to death and the values of 43 different clinical and pathological parameters. Studies were performed using data from 334 elderly, longitudinally evaluated research subjects who had undergone autopsy and satisfied inclusion criteria from an initial study group of 501. Interindividual variance in MMSE scores was used as a surrogate for the severity of cognitive impairment linked to aging (CILA). A statistical linear regression-based model provided a framework for assessing the parameters with significant, direct impact on CILA severity. Strong association between CILA and Alzheimer's disease (AD) pathology, especially isocortical neurofibrillary tangles, was evident. The pattern of association between AD lesion densities with cognitive impairment severity was biologically informative, with neuritic plaques having more impact in relatively high-functioning individuals. Abundant isocortical Lewy bodies tended to be an additive pathology correlating with final MMSE scores approximately 10 points lower. In a subset of cases we found evidence for association between TDP-43-related pathology and CILA severity, independent of AD or hippocampal sclerosis. There was no support for independent association between CILA severity and most evaluated indices including diffuse plaques, argyrophilic grains, heart disease, education level, apolipoprotein E alleles or diabetes.
引用
收藏
页码:66 / 79
页数:14
相关论文
共 131 条
[1]   Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field:: Relationship with the progression of Alzheimer's disease [J].
Akram, Afia ;
Christoffel, Daniel ;
Rocher, Anne B. ;
Bouras, Constantin ;
Koevari, Enikoe ;
Perl, Daniel P. ;
Morrison, John H. ;
Herrmann, Francois R. ;
Haroutunian, Vahram ;
Giannakopoulos, Panteleimon ;
Hof, Patrick R. .
NEUROBIOLOGY OF AGING, 2008, 29 (09) :1296-1307
[2]   TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease [J].
Amador-Ortiz, Catalina ;
Lin, Wen-Lang ;
Ahmed, Zeshan ;
Personett, David ;
Davies, Peter ;
Dara, Ranjan ;
Graff-Radford, Neill R. ;
Hutton, Michael L. ;
Dickson, Dennis W. .
ANNALS OF NEUROLOGY, 2007, 61 (05) :435-445
[3]   Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration [J].
Amador-Ortiz, Catalina ;
Ahmed, Zeshan ;
Zehr, Cynthia ;
Dickson, Dennis W. .
ACTA NEUROPATHOLOGICA, 2007, 113 (03) :245-252
[4]   TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis [J].
Arai, Tetsuaki ;
Hasegawa, Masato ;
Akiyama, Haruhiko ;
Ikeda, Kenji ;
Nonaka, Takashi ;
Mori, Hiroshi ;
Mann, David ;
Tsuchiya, Kuniaki ;
Yoshida, Marl ;
Hashizume, Yoshio ;
Oda, Tatsuro .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 351 (03) :602-611
[5]   Quantifying the pathology of neurodegenerative disorders: quantitative measurements, sampling strategies and data analysis [J].
Armstrong, RA .
HISTOPATHOLOGY, 2003, 42 (06) :521-529
[6]   NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE [J].
ARRIAGADA, PV ;
GROWDON, JH ;
HEDLEYWHYTE, ET ;
HYMAN, BT .
NEUROLOGY, 1992, 42 (03) :631-639
[7]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER LESIONS AND INTELLECTUAL STATUS IN ALZHEIMERS AND PARKINSONS-DISEASE PATIENTS [J].
BANCHER, C ;
BRAAK, H ;
FISCHER, P ;
JELLINGER, KA .
NEUROSCIENCE LETTERS, 1993, 162 (1-2) :179-182
[8]   Correlations between mental state and quantitative neuropathology in the Vienna longitudinal study on dementia [J].
Bancher, C ;
Jellinger, K ;
Lassmann, H ;
Fischer, P ;
Leblhuber, F .
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, 1996, 246 (03) :137-146
[9]   Clinical dementia rating performed several years prior to death predicts regional Alzheimer's neuropathology [J].
Beeri, Michal Schnaider ;
Silverman, Jeremy M. ;
Schmeidler, James ;
Wysocki, Michael ;
Grossman, Hillel Z. ;
Purohit, Dushyant P. ;
Perl, Daniel P. ;
Haroutunian, Vahram .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2008, 25 (05) :392-398
[10]   Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people [J].
Bennett, DA ;
Schneider, JA ;
Wilson, RS ;
Bienias, JL ;
Berry-Kravis, E ;
Arnold, SE .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2005, 76 (09) :1194-1199