Automated analysis of written language in the three variants of primary progressive aphasia.

Despite the important role of written language in everyday life, abnormalities in functional written communication have been sparsely investigated in primary progressive aphasia. Prior studies have analysed written language separately in each of the three variants of primary progressive aphasia-but have rarely compared them to each other or to spoken language. Manual analysis of written language can be a time-consuming process. We therefore developed a program that quantifies content units and total units in written or transcribed language samples. We analysed written and spoken descriptions of the Western Aphasia Battery picnic scene, based on a predefined content unit corpus. We calculated the ratio of content units to units as a measure of content density. Our cohort included 115 participants (20 controls for written, 20 controls for spoken, 28 participants with nonfluent variant primary progressive aphasia, 30 for logopenic variant and 17 for semantic variant). Our program identified content units with a validity of 99.7% (95%CI 99.5-99.8). All patients wrote fewer units than controls (P < 0.001). Patients with the logopenic variant (P = 0.013) and the semantic variant (0.004) wrote fewer content units than controls. The content unit-to-unit ratio was higher in the nonfluent and semantic variants than controls (P = 0.019), but no difference in the logopenic variant (P = 0.962). Participants with the logopenic (P < 0.001) and semantic (P = 0.04) variants produced fewer content units in written compared to spoken descriptions. All variants produced fewer units in written samples compared to spoken (P < 0.001). However, due to a relatively smaller decrease in written content units, we observed a larger content unit-to-unit ratio in writing over speech (P < 0.001). Written and spoken content units (r = 0.5, P = 0.009) and total units (r = 0.64, P < 0.001) were significantly correlated in patients with nonfluent variant, but this was not the case for logopenic or semantic. Considering all patients with primary progressive aphasia, fewer content units were produced in those with greater aphasia severity (Progressive Aphasia Severity Scale Sum of Boxes, r = -0.24, P = 0.04) and dementia severity (Clinical Dementia Rating scale Sum of Boxes, r = -0.34, P = 0.004). In conclusion, we observed reduced written content in patients with primary progressive aphasia compared to controls, with a preference for content over non-content units in patients with the nonfluent and semantic variants. We observed a similar 'telegraphic' style in both language modalities in patients with the nonfluent variant. Lastly, we show how our program provides a time-efficient tool, which could enable feedback and tracking of writing as an important feature of language and cognition.

Feasibility of multidisciplinary telehealth evaluations in atypical dementia.

INTRODUCTION: While cognitive assessment by videoconference has become possible over the past decade, the COVID-19 pandemic underscores the critical need for expansion and examination of these methods, their appropriateness for various patient populations, and their benefits and limitations. Validity and reliability studies of tele-neuropsychological testing have been conducted in MCI or mild AD dementia patients (e.g., MMSE=25+); few studies have assessed the feasibility of neurologic examination by video, and none in atypical dementias, assuming that patients with some types (e.g., language, comportment) or greater severity of cognitive-behavioral impairment would be unable to participate. Here we report the feasibility of telehealth services for a multi-disciplinary dementia subspecialty clinic that include cognitive-behavioral and neurologic assessment with patients with atypical neurodegenerative syndromes. METHODS: 104 patient-carepartner (P-C) dyads met with providers in the MGH FTD Unit by videoconference (March-December, 2020) for routine clinical care. P-Cs completed validated questionnaires assessing cognition-mood/behavior/function on REDCap prior to video clinical interview and cognitive assessment, including the MoCA and Boston Cognitive Exam (BCE2.0), a newly revised brief cognitive assessment battery adapted for telehealth. P-Cs met with a neurologist for a basic neurologic examination (including eye-movement examination), review of assessment results, and discussion of care plan. P-Cs completed a satisfaction survey. RESULTS: The 104 P-Cs included a range of atypical neurodegenerative disorders (bvFTD, PCA, PPA, CBS, PSP, eoAD, Multidomain syndrome) mild-to-severe impairment (CDR range: 0-3). 76% completed the MoCA (25% had CDR=2). 36% also completed the BCEv2. Comparison of remote assessment data to previous in-person testing is ongoing. Of P-Cs who completed a satisfaction survey, all reported being "very satisfied" with the appointment, with 93% open to participating in a remote visit again. 87% found the telehealth visit comparable to an in-person visit. 66% preferred a future combination of remote and in-person visits. CONCLUSIONS: Multi-disciplinary telehealth visits appear to be feasible with patients with atypical cognitive-behavioral syndromes of across the severity spectrum. P-Cs report a high degree of satisfaction with the telehealth visit and an openness to ongoing telehealth visits. Results have implications for increasing accessibility of multidisciplinary medical services for patients and families living with complex forms of dementia.

Associations of MAP2K3 Gene Variants With Superior Memory in SuperAgers.

Introduction: SuperAgers are adults age 80+ with episodic memory performance that is at least as good as that of average middle-aged adults. Understanding the biological determinants of SuperAging may have relevance to preventing age-related cognitive decline and dementia. This study aimed to identify associations between genetic variations and the SuperAging phenotype using Whole Exome Sequencing (WES). Methods: Sequence Kernel Association Combined (SKAT-C) test was conducted at the gene level including both rare and common variants in 56 SuperAgers and 22 cognitively-average controls from the Alzheimer's disease Neuroimaging Initiative (ADNI). Results: The SuperAging phenotype was associated with variants in the Mitogen-Activated Protein Kinase Kinase 3 (MAP2K3) gene. Three single nucleotide polymorphisms (SNPs) contributed to the significance (rs2363221 [intron 1], rs2230435 [exon 5], rs736103 [intron 7]). Conclusions: MAP2K3 resides in a biological pathway linked to memory. It is in a signaling cascade associated with beta-amyloid mediated apoptosis and has enriched expression in microglia. This preliminary work suggests MAP2K3 may represent a novel therapeutic target for age-related memory decline and perhaps Alzheimer's disease (AD).

Psychological well-being in elderly adults with extraordinary episodic memory.

OBJECTIVES: The Northwestern University SuperAging Program studies a rare cohort of individuals over age 80 with episodic memory ability at least as good as middle-age adults to determine what factors contribute to their elite memory performance. As psychological well-being is positively correlated with cognitive performance in older adults, the present study examined whether aspects of psychological well-being distinguish cognitive SuperAgers from their cognitively average-for-age, same-age peers. METHOD: Thirty-one SuperAgers and 19 cognitively average-for-age peers completed the Ryff 42-item Psychological Well-Being questionnaire, comprised of 6 subscales: Autonomy, Positive Relations with Others, Environmental Mastery, Personal Growth, Purpose in Life, and Self-Acceptance. RESULTS: The groups did not differ on demographic factors, including estimated premorbid intelligence. Consistent with inclusion criteria, SuperAgers had better episodic memory scores. Compared to cognitively average-for-age peers, SuperAgers endorsed greater levels of Positive Relations with Others. The groups did not differ on other PWB-42 subscales. DISCUSSION: While SuperAgers and their cognitively average-for-age peers reported similarly high levels of psychological well-being across multiple dimensions, SuperAgers endorsed greater levels of positive social relationships. This psychological feature could conceivably have a biological relationship to the greater thickness of the anterior cingulate gyrus and higher density of von Economo neurons previously reported in SuperAgers.