Background: Primary Progressive Aphasia (PPA) is a syndrome characterized by an isolated impairment of language function at disease onset. The cholinergic system is implicated in language function and cholinergic deficits are seen in the brains of individuals with PPA. One major source of cholinergic innervation of the cerebral cortex is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). This nucleus is postulated to be involved in language function. We compared the abundance of cholinergic neurons in the NBM and NSP of controls and individuals with PPA. Also explored was whether the individuals presenting with PPA, who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Methods: Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n = 5) and PPA (n = 5) brains. Choline acetyltransferase (ChAT) immunohistochemical staining labeled cholinergic neurons were quantified using Neurolucida software. Results: In comparison to matched controls, PPA showed reduction of cholinergic neurons in the NBM (t(8) = 4.04, p = 0.0037; Cohen’s effect size value d = 2.62) and the NSP (t(6) = 4.62, p = 0.0042; Cohen’s d effect size d = 2.92). The average percent of cholinergic neuronal loss was relatively higher in the NSP (64.7%) compared to the NBM (47.7%). Conclusion: Regardless of underlying pathology, all cases presenting with PPA showed a marked loss of cholinergic neurons in the NSP, providing further evidence for the importance of this nucleus in language function.

The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer’s disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype. (JINS, 2010, 16, 278–286.)