Non-Verbal Episodic Memory Deficits in Primary Progressive Aphasias are Highly Predictive of Underlying Amyloid Pathology

Ramanan, Siddharth; Flanagan, Emma; Leyton, Cristian E.; Villemagne, Victor L.; Rowe, Christopher C.; Hodges, John R.; Hornberger, Michael

doi:10.3233/jad-150752

Cited by 39 publications

(40 citation statements)

References 23 publications

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“…Our result of impairment in delayed visual recall in the lvPPA group supports the similar finding by Ramanan et al (2016) but extends the finding to include the domain of visual delayed recall; a finding that may relate to Alzheimer’s disease targeting medial temporal lobe structures (Ossenkoppele et al, 2015). …”

Section: Discussionsupporting

confidence: 88%

Visuospatial Functioning in the Primary Progressive Aphasias

Watson

Possin

Allen

et al. 2017

J Int Neuropsychol Soc

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Objectives The aim of this study was to identify whether the three main primary progressive aphasia (PPA) variants would show differential profiles on measures of visuospatial cognition. We hypothesized that the logopenic variant would have the most difficulty across tasks requiring visuospatial and visual memory abilities. Methods PPA patients (n = 156), diagnosed using current criteria, and controls were tested on a battery of tests tapping different aspects of visuospatial cognition. We compared the groups on an overall visuospatial factor; construction, immediate recall, delayed recall, and executive functioning composites; and on individual tests. Cross-sectional and longitudinal comparisons were made, adjusted for disease severity, age, and education. Results The logopenic variant had significantly lower scores on the visuospatial factor and the most impaired scores on all composites. The nonfluent variant had significant difficulty on all visuospatial composites except the delayed recall, which differentiated them from the logopenic variant. In contrast, the semantic variants performed poorly only on delayed recall of visual information. The logopenic and nonfluent variants showed decline in figure copying performance over time, whereas in the semantic variant, this skill was remarkably preserved. Conclusions This extensive examination of performance on visuospatial tasks in the PPA variants solidifies some previous findings, for example, delayed recall of visual stimuli adds value in differential diagnosis between logopenic variant PPA and nonfluent variant PPA variants, and illuminates the possibility of common mechanisms that underlie both linguistic and non-linguistic deficits in the variants. Furthermore, this is the first study that has investigated visuospatial functioning over time in the PPA variants.

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Section: Discussionsupporting

confidence: 88%

Visuospatial Functioning in the Primary Progressive Aphasias

Watson

Possin

Allen

et al. 2017

J Int Neuropsychol Soc

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“…Evaluating verbal episodic memory performance in lvPPA may pose a challenge. Indeed, reports of verbal episodic memory performance in lvPPA have been inconsistent, with some reporting impaired memory (Flanagan et al, 2014; Piguet et al, 2015; Ramanan et al, 2016) and one study observing equally impaired verbal episodic memory and recognition memory in AD and lvPPA patients who also had visual memory difficulty (Ramanan et al, 2016), while others found no deficit (Weintraub et al, 2013; Mesulam et al, 2014b). …”

Section: Discussionmentioning

confidence: 99%

Neural Correlates of Verbal Episodic Memory and Lexical Retrieval in Logopenic Variant Primary Progressive Aphasia

et al. 2017

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Objective: Logopenic variant primary progressive aphasia (lvPPA) is commonly associated with Alzheimer's disease (AD) pathology. But lvPPA patients display different cognitive and anatomical profile from the common clinical AD patients, whose verbal episodic memory is primarily affected. Reports of verbal episodic memory difficulty in lvPPA are inconsistent, and we hypothesized that their lexical retrieval impairment contributes to verbal episodic memory performance and is associated with left middle temporal gyrus atrophy.Methods: We evaluated patients with lvPPA (n = 12) displaying prominent word-finding and repetition difficulties, and a demographically-matched cohort of clinical Alzheimer's disease (AD, n = 26), and healthy seniors (n = 16). We assessed lexical retrieval with confrontation naming and verbal episodic memory with delayed free recall. Whole-brain regressions related naming and delayed free recall to gray matter atrophy. Medial temporal lobe (MTL) subfields were examined using high in-plane resolution imaging.Results: lvPPA patients had naming and delayed free recall impairments, but intact recognition memory. In lvPPA, delayed free recall was related to naming; both were associated with left middle temporal gyrus atrophy but not MTL atrophy. Despite cerebrospinal fluid evidence consistent with AD pathology, examination of MTL subfields revealed no atrophy in lvPPA. While AD patients displayed impaired delayed free recall, this deficit did not correlate with naming. Regression analyses related delayed free recall deficits in clinical AD patients to MTL subfield atrophy, and naming to left middle temporal gyrus atrophy.Conclusion: Unlike amnestic AD patients, MTL subfields were not affected in lvPPA patients. Verbal episodic memory deficit observed in lvPPA was unlikely to be due to a hippocampal-mediated mechanism but appeared to be due to poor lexical retrieval. Relative sparing of MTL volume and intact recognition memory are consistent with previous reports of hippocampal-sparing variant cases of AD pathology, where neurofibrillary tangles are disproportionately distributed in cortical areas with relative sparing of the hippocampus. This suggests that AD neuropathology in lvPPA may originate in neuronal networks outside of the MTL, which deviates from the typical Braak staging pattern of spreading pathology in clinical AD.

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“…Significant socioemotional dysfunction including loss of empathy and impaired emotion detection abilities has also been documented (Hazelton et al, 2017;Multani et al, 2017;Fittipaldi et al, 2019). Finally, LPA patients demonstrate significant verbal episodic memory difficulties (Butts et al, 2015;Casaletto et al, 2017;Win et al, 2017;Eikelboom et al, 2018) comparable to that observed in typical Alzheimer's disease (Ramanan et al, 2016).…”

Section: Introductionmentioning

confidence: 96%

“…While such deficits could manifest simply as a by-product of language and lexical retrieval difficulties in LPA, compromised performance on tasks with minimal language demands suggests otherwise. For example, LPA patients show significant impairments on nonverbal tasks of episodic memory (Ramanan et al, 2016), spatial span Foxe et al, 2016), spatial orientation (Magnin et al, 2013), and visuospatial processing (Butts et al, 2015;Watson et al, 2018), all of which circumvent language demands. Moreover, impairments on nonverbal episodic memory and emotion processing in LPA have been shown to persist when disease severity and language dysfunction are controlled for (Ramanan et al, 2016;Multani et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…For example, LPA patients show significant impairments on nonverbal tasks of episodic memory (Ramanan et al, 2016), spatial span Foxe et al, 2016), spatial orientation (Magnin et al, 2013), and visuospatial processing (Butts et al, 2015;Watson et al, 2018), all of which circumvent language demands. Moreover, impairments on nonverbal episodic memory and emotion processing in LPA have been shown to persist when disease severity and language dysfunction are controlled for (Ramanan et al, 2016;Multani et al, 2017). Clinical and carer reports further corroborate these findings, with the majority of LPA patients presenting with visible extra-linguistic general cognitive difficulties (Owens et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Establishing two principal dimensions of cognitive variation in Logopenic Progressive Aphasia

Ramanan

Roquet

Goldberg

et al. 2019

Preprint

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Running title: Distinct cognitive profiles in LPA Word count (abstract): 394 words Word count (manuscript): 6,258 words Number of tables (manuscript): 3 Number of figures (manuscript): 5 Total number of display items (manuscript): 8 Supplementary material: 1 supplementary file with supplementary methods, tables, and figures Number of tables (supplementary): 4 Number of figures (supplementary): 4ABSTRACT Logopenic Progressive Aphasia is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal brain atrophy.Mapping of the clinical phenomenology of this syndrome has largely concentrated on its language deficits. Accumulating evidence, however, points to the presence of cognitive deficits, even on cognitive tasks with minimal language demands. Traditionally, nonlinguistic cognitive deficits in Logopenic Progressive Aphasia have been thought to scale with advancing disease severity. When grouped according to the severity of language dysfunction, however, subgroups of Logopenic Progressive Aphasia frequently display overlapping cognitive profiles, suggesting individual-level systematic variation in nonlinguistic cognitive performance that may be independent of primary language dysfunction.To address this issue, we used principal component analysis to decompose variation in cognitive performance at an individual level, in a large, well-characterised cohort of Logopenic Progressive Aphasia patients (N = 43). Patients underwent detailed, standardised neuropsychological assessments of language, memory, executive and visuospatial functioning, in addition to structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected 'speech production and verbal memory' deficits which typify Logopenic Progressive Aphasia. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes -domains previously thought to be affected later in the disease stage. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable speech production and verbal memory factor scores, regardless of their severity, diverge considerably on visuoexecutive test performance, underscoring the inherent inter-individual variability in cognitive profiles in comparably 'logopenic' patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, Logopenic Progressive Aphasia patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temp...

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Non-Verbal Episodic Memory Deficits in Primary Progressive Aphasias are Highly Predictive of Underlying Amyloid Pathology

Cited by 39 publications

References 23 publications

Visuospatial Functioning in the Primary Progressive Aphasias

Visuospatial Functioning in the Primary Progressive Aphasias

Neural Correlates of Verbal Episodic Memory and Lexical Retrieval in Logopenic Variant Primary Progressive Aphasia

Establishing two principal dimensions of cognitive variation in Logopenic Progressive Aphasia

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