Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia

被引:364
作者
Mesulam, Marsel [1 ,2 ]
Wicklund, Alissa [1 ]
Johnson, Nancy [1 ,2 ]
Rogalski, Emily [1 ]
Leger, Gabriel C. [1 ]
Rademaker, Alfred [1 ,3 ]
Weintraub, Sandra [1 ,2 ]
Bigio, Eileen H. [1 ,4 ]
机构
[1] Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL USA
[2] Northwestern Univ, Feinberg Sch Med, Dept Psychiat, Chicago, IL 60611 USA
[3] Northwestern Univ, Feinberg Sch Med, Dept Publ Hlth, Chicago, IL 60611 USA
[4] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA
关键词
D O I
10.1002/ana.21388
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype. Methods: Neuropsychological and neuropathological analyses of 23 consecutive PPA autopsies. All had qualitative determination of neurofibrillary tangle (NFT) density. Additional quantitation was done in four of the PPA/AD cases and four AD cases with the typical amnestic dementia of the Alzheimer type. Results: The sample contained mostly logopenic, agrammatic, and mixed forms of PPA. All six agrammatics had frontotemporal lobar degeneration (five of six with tauopathy). Seven of the 11 logopenics had AD. In logopenics, lower memory scores increased the probability of AD, but there were exceptions. The PPA/AD group showed predominance of entorhinal NFT typical of the amnestic dementia of the Alzheimer type. In the small subgroup examined quantitatively, neocortical NFTs were more numerous in the left hemisphere of PPA/AD. However, the asymmetry was low and inconsistent. Neuritic plaques did not display consistent asymmetry. Apolipoprotein E4, a major risk factor for typical AD, did not predict AD pathology in PPA. Interpretation: Subtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level. However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients. The inconsistent concordance of NFT distribution with the asymmetric atrophy and the nonamnestic phenotype also raises the possibility that the AD markers encountered at autopsy in PPA may not always reflect the nature of the initiating neurodegenerative process.
引用
收藏
页码:709 / 719
页数:11
相关论文
共 57 条
[41]   The uniform data set (UDS): Clinical and cognitive variables and descriptive data from Alzheimer disease centers [J].
Morris, John C. ;
Weintraub, Sandra ;
Chui, Helena C. ;
Cummings, Jeffrey ;
DeCarli, Charles ;
Ferris, Steven ;
Foster, Norman L. ;
Galasko, Douglas ;
Graff-Radford, Neill ;
Peskind, Elaine R. ;
Beekly, Duane ;
Ramos, Erin M. ;
Kukull, Walter A. .
ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2006, 20 (04) :210-216
[42]   Argyrophilic thorny astrocyte clusters in association with Alzheimer's disease pathology in possible primary progressive aphasia [J].
Munoz, David G. ;
Woulfe, John ;
Kertesz, Andrew .
ACTA NEUROPATHOLOGICA, 2007, 114 (04) :347-357
[43]   Frontotemporal lobar degeneration - A consensus on clinical diagnostic criteria [J].
Neary, D ;
Snowden, JS ;
Gustafson, L ;
Passant, U ;
Stuss, D ;
Black, S ;
Freedman, M ;
Kertesz, A ;
Robert, PH ;
Albert, M ;
Boone, K ;
Miller, BL ;
Cummings, J ;
Benson, DF .
NEUROLOGY, 1998, 51 (06) :1546-1554
[44]   Aβ amyloid deposition in the language system and how the brain responds [J].
Nelissen, Natalie ;
Vandenbulcke, Mathieu ;
Fannes, Katrien ;
Verbruggen, Alfons ;
Peeters, Ronald ;
Dupont, Patrick ;
Van Laere, Koen ;
Borman, Guy ;
Vandenberghe, Rik .
BRAIN, 2007, 130 :2055-2069
[45]   An update on primary progressive aphasia [J].
Rogalski, Emily ;
Mesulam, Marsel .
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2007, 7 (05) :388-392
[46]   Semantic dementia with ubiquitin-positive tau-negative inclusion bodies [J].
Rossor, MN ;
Revesz, T ;
Lantos, PL ;
Warrington, EK .
BRAIN, 2000, 123 :267-276
[47]   Frontotemporal lobar degeneration: clinical and pathological relationships [J].
Snowden, Julie ;
Neary, David ;
Mann, David .
ACTA NEUROPATHOLOGICA, 2007, 114 (01) :31-38
[48]   Primary Progressive Aphasia: PPA and the language network [J].
Sonty, SP ;
Mesulam, MM ;
Thompson, CK ;
Johnson, NA ;
Weintraub, S ;
Parrish, TB ;
Gitelman, DR .
ANNALS OF NEUROLOGY, 2003, 53 (01) :35-49
[49]  
Strauss E., 2006, COMPENDIUM NEUROPSYC, DOI DOI 10.1080/09084280701280502
[50]   Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy [J].
Tang-Wai, DF ;
Graff-Radford, NR ;
Boeve, BF ;
Dickson, DW ;
Parisi, JE ;
Crook, R ;
Caselli, RJ ;
Knopman, DS ;
Petersen, RC .
NEUROLOGY, 2004, 63 (07) :1168-1174