biostudies-literature00580Giannini LAANIA NIH HHSNINDS NIH HHS2276-2284https://www.ebi.ac.uk/biostudies/studies/S-EPMC5567322biostudies-literatureUnknown88(24)<h4>Objective</h4>To determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA).<h4>Methods</h4>We performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data.<h4>Results</h4>A total of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13 frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%) patients with AD had a logopenic spectrum phenotype; 5 met published criteria for the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits (lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA-). Sentence repetition was impaired in 68% of patients with PPA with AD pathology; forward digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA (33%, <i>p</i> < 0.01). Lexical retrieval difficulty was common in all patients with PPA and did not discriminate between groups. Compared to non-AD, PPA with AD pathology had elevated microscopic neurodegenerative pathology in the superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (<i>p</i> < 0.01). Low DF scores correlated with high microscopic pathologic burden in superior/midtemporal and angular gyri (<i>p</i> ≤ 0.03).<h4>Conclusions</h4>Phonologic loop dysfunction is a central feature of AD-associated PPA and specifically correlates with temporoparietal neurodegeneration. Quantitative measures of phonologic loop function, combined with modified clinical lvPPA criteria, may help discriminate AD-associated PPA.NeurologyClinical marker for Alzheimer disease pathology in logopenic primary progressive aphasia.PMC5567322P30 AG010124R01 AG038490K23 NS088341K01 AG043503P01 AG017586Ash SGrossman MIrwin DJMcMillan CTVan Deerlin VMGiannini LAATrojanowski JQRascovsky KLee EBWolk DA58falseClinical marker for Alzheimer disease pathology in logopenic primary progressive aphasia.<h4>Objective</h4>To determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA).<h4>Methods</h4>We performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data.<h4>Results</h4>A total of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13 frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%) patients with AD had a logopenic spectrum phenotype; 5 met published criteria for the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits (lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA-). Sentence repetition was impaired in 68% of patients with PPA with AD pathology; forward digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA (33%, <i>p</i> < 0.01). Lexical retrieval difficulty was common in all patients with PPA and did not discriminate between groups. Compared to non-AD, PPA with AD pathology had elevated microscopic neurodegenerative pathology in the superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (<i>p</i> < 0.01). Low DF scores correlated with high microscopic pathologic burden in superior/midtemporal and angular gyri (<i>p</i> ≤ 0.03).<h4>Conclusions</h4>Phonologic loop dysfunction is a central feature of AD-associated PPA and specifically correlates with temporoparietal neurodegeneration. Quantitative measures of phonologic loop function, combined with modified clinical lvPPA criteria, may help discriminate AD-associated PPA.2017-01-01T00:00:00Z2017 Jun2024-11-13T02:05:36.246Z2019-03-26T23:41:09ZS-EPMC55673222851526510.1212/WNL.000000000000403410.1212/wnl.0000000000004034