Comorbid Neurodegeneration in Primary Progressive Aphasia: Clinicopathological Correlations in a Single-Center Study

Table 2

Attribution of clinical PPA subtypes based on an evaluation of language alteration and neuropathological summary. Key aphasia features respective to the PPA subtype are italicized for each patient.

Case	PPA subtype	Language impairment characteristics	Neuropathology findings
1	nfvPPA	Declining speech fluency and reduced vocabulary (marked lexical retrieval problems). Late severely impaired language production and comprehension	Combination of both AD (A3B3C3) and DLB (McKeith II, Braak 5); focal and relatively prominent vascular changes
2	nfvPPA	Initially, word-finding difficulties and comprehension difficulties for complex sentences. Progressive reduction in verbal production with anomic pauses and dysarthria	Combination of AD (A3B3C3) with marked cerebral amyloid angiopathy and DLB (McKeith III, Braak 6)
3	nfvPPA	Diminished verbal expression, impaired repetition of multisyllabic words (speech apraxia), with only monosyllabic vocalization preserved. Late severely impaired sentence comprehension, with partially preserved single-word comprehension	Combination of AD (A2B2C2) and multisystemic FTLD-tau with predominant PSP (Williams score 6-7) and hallmarks of GGT and ARTAG
4	nfvPPA	Early impaired lexical retrieval in spontaneous speech and sentence comprehension. With disease progression, there was increasingly limited speech output	Combination of AD (A3B3C3) with limbic-predominant depositions of TDP-43 (LATE)
5	nfvPPA	Severe anomia reduced syntactic complexity in production with marked agrammatism, impaired sentence comprehension, relatively preserved repetition skills. Speech apraxia	Combination of AD (A3B3C3) with marked cerebral amyloid angiopathy and FTLD-TDP type A (based on the harmonized Mackenzie classification)
6	Progressive dysarthria, later nfvPPA	Progressive dysarthria with initially only very mild language involvement (mostly decreased verbal communication). Later progressed to severe dementia near mutism	AD (A3B3C3) with variable vascular changes
7	Mixed; (nfvPPA+svPPA)	Severely reduced speech production and mild anomia. Progressively lexical retrieval problems, speech apraxia, and agrammatism during spontaneous speech. Late comprehension impairment at the single word and sentence levels. Even later lost comprehension skills and almost mutism	Combination of GGT type I with deposits of TDP-43 protein consistent with LATE
8	svPPA	Early impairment in production (anomia) and severe comprehension problems even at the single word level. Late mutism with only perseverative vocalizations	Combination of AD (A3B3C3) with multisystemic FTLD-tau: predominant PSP (Williams score 6-7), hallmarks of GGT and ARTAG; together with TDP-43 protein deposits consistent with LATE
9	lvPPA	Worsening speech fluency, word-finding difficulties, mild phonemic paraphasia; without comprehension impairment. Late impairment in production and speech comprehension	Combination of early-onset AD (A3B3C3) and DLB (McKeith III, Braak 6). Genetic analysis found a presenilin mutation (PS1 gene)