Diagnosing non-fluent/agrammatic variant primary progressive aphasia (nfvPPA) relies primarily on apraxia of speech (AOS) and agrammatism. However, differentiating phonetic-level (articulatory) from phonemic-level (phonological) impairments remains clinically challenging, especially in advanced stages. We report a 65-year-old Japanese male with nfvPPA who had become virtually speechless (ἀφημί). Leveraging the Kana writing system's one-to-one correspondence to morae, we designed a cross-modal experiment to isolate his underlying deficit. Speech production was evaluated across four conditions: picture naming, Kanji word reading, Kana word reading, and character-by-character Kana reading. Statistical analysis was performed using Fisher's exact test and adjusted residual analysis. Speech intelligibility significantly improved during character-by-character Kana reading compared to other modalities. Residual analysis confirmed that explicit moraic cues markedly reduced error rates. These findings indicate that our approach effectively unmasked superimposed phonemic-level retrieval deficits contributing to speechlessness in nfvPPA. This study highlights the utility of Japanese orthography in disentangling underlying mechanisms and demonstrates that moraic assistance can serve as a potent facilitation strategy in severe cases.
To assess the possibility that individualized duration of donanemab treatment might enable early pausing of therapy, and to explore the possible utility of plasma P-tau217 as a biomarker for treatment response monitoring in real-time, two unrelated patients with early-stage Alzheimer's disease were treated with donanemab at the Icahn School of Medicine at Mount Sinai. Clinical progress was monitored via medical chart review, including serial brain MRI, amyloid PET scans, and blood-based biomarker assays (Quanterix Simoa® and Fujirebio Lumipulse®). Both patients achieved complete amyloid clearance as judged by amyloid PET prior to their 6th and 9th infusions, which were significantly earlier than the 12-month mark typically recommended for follow-up amyloid assessment. In agreement with the amyloid PET, concurrently measured plasma P-tau217 levels fell within a low range. Treatment was discontinued for both patients. These patients highlight the possibility of individualized treatment durations for anti-amyloid therapy with donanemab, guided by biomarker response. Early cessation following rapid plaque clearance could reduce healthcare costs and minimize exposure to the risk of amyloid-related imaging abnormalities and the generation of neutralizing antibodies. Plasma P-tau217 warrants further investigation as a reliable, cost-effective surrogate for PET scans to monitor real-time treatment response and guide the timing of discontinuation.
Hereditary spastic paraplegia (HSP) is a group of genetic disorders caused by >80 genes that can be described as either pure or complex forms.We report a case of a patient with a complex form of SPG7 with significant cognitive impairment.A 42-year-old man presented with a 10-year history of dysarthria, 5 years of gait difficulties, and 3 years of cognitive symptoms. Neuropsychological analysis showed deficits involving speed of information processing, mental flexibility, ideational fluency, verbal concept formation, visual working memory, and visual-spatial perception. Next-generation sequencing on whole blood revealed 2 heterozygous pathogenic variants in SPG7 (c. 1049_1077del, p. Pro350Glnfs*36 and c. 1529C>T, p. Ala510Val).There are emerging reports of complex forms of SPG7 presenting with impairments in memory, executive dysfunction, language, visuospatial processing, social functioning, and emotional communication. In this report, we describe a complex SPG7 patient who underwent formal neuropsychological testing to assess cognitive status in depth. This revealed deficits in speed of processing, visuospatial working memory and perception, impaired non-verbal intellect, and overall lack of insight, which have not yet been described in the literature.
Choroid plexus xanthogranulomas are rare, typically incidental intraventricular lesions that infrequently become symptomatic. When symptomatic, they most often present with headache or hydrocephalus, whereas cognitive sequelae and postoperative neuropsychological outcomes remain poorly characterized. A 63-year-old right-handed man with bilateral trigonal intraventricular lesions, larger on the right, presented with headaches and a history of subjective progressive memory complaints. He underwent resection of the right-sided lesion through a right temporoparietal approach. Immediately after surgery, he developed a severe and persistent amnestic-cognitive syndrome with profound inability to retain new information, confabulation, reduced insight, and marked remote-memory disturbance. Neuropsychological evaluation 3 months postoperatively demonstrated severe anterograde impairment in verbal learning and delayed visuospatial recall, together with substantial retrograde memory impairment involving autobiographical episodic recollection, personal semantic memory, and public semantic knowledge. This case suggests that bilateral trigonal xanthogranulomas and their surgical treatment may place distributed memory networks at substantial risk. Because formal preoperative neuropsychological testing and direct review of the original preoperative MRI were unavailable, the relative contributions of preexisting bilateral disease burden and postoperative network disruption cannot be fully separated. The case supports broader baseline cognitive assessment, precise laterality-specific surgical description, and structured postoperative neuropsychological follow-up for lesions near posterior medial and limbic white-matter pathways.
Alexander disease (AxD) is a rare progressive astrogliopathy and leukodystrophy caused by heterozygous pathogenic variants in the gene encoding glial fibrillary acidic protein (GFAP). Cognitive problems in AxD have long been recognized, but domain-specific neuropsychological descriptions of adult-onset Alexander disease (AO-AxD) remain sparse. We report a genetically confirmed 53-year-old man with AO-AxD who underwent comprehensive neuropsychological assessment because of progressive cognitive and behavioral complaints. The profile was characterized by deficient verbal episodic memory retrieval and reduced set-shifting efficiency, with relatively preserved recognition memory, language, visuospatial abilities, and most attentional measures. Structural MRI showed characteristic medullary and upper cervical cord involvement but only limited supratentorial white matter abnormalities. To contextualize the case, we reviewed published AO-AxD reports with domain-specific neuropsychological testing. The available literature remains limited and heterogeneous, but suggests that cognitive manifestations in AO-AxD may include retrieval-based memory deficits, executive inefficiency, and visuospatial difficulties. We discuss these findings in relation to white matter dementia, fronto-subcortical and fronto-hippocampal network dysfunction, and potential astrocyte-mediated mechanisms.
