P4‐107: Genetic risk factors for posterior cortical atrophy may be distinct from late‐onset Alzheimer's disease

Schott, Jonathan M.; Crutch, Sebastian J.; Uphill, James; Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Yong, Keir; Rossor, Martin N.; Fox, NC; Mead, Simon

doi:10.1016/j.jalz.2012.05.1810

Cited by 6 publications

(9 citation statements)

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“…The greatest selectivity of domain association in this study was within lvPPA, in which all 21 patients with LDs had language-based LDs (including 2 with a comorbid mathematical LD), raising the possibility that this domain association is largely driven by the strength of association within the lvPPA cohort; nevertheless, other investigations lend support to our claims of a selective association between mathematical and visuospatial differences in PCA. A genomewide association study 35 of PCA identified 3 novel putative gene targets, 2 of which are involved in neurodevelopment, including 1 that plays a notable role in the maturation of the visual system. Furthermore, a series that investigated LDs in AD and frontotemporal dementia examined 85 patients with typical amnestic AD and 17 with atypical AD presentations, including 3 with lvPPA and 3 with PCA, and found increased prevalence of LDs in the atypical AD group.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy

et al. 2018

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IMPORTANCE Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation. OBJECTIVE To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017. MAIN OUTCOMES AND MEASURES Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts. RESULTS A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD) were included in the study. The groups were not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3% female; lvPPA, 56.0% female; amnestic AD, 57.0% female; P = .30) but differed on non–right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3% white; lvPPA, 99.0% white; amnestic AD, 80.0% white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0% expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this rate was greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of glob...

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Section: Discussionmentioning

confidence: 99%

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy

et al. 2018

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“…However, the exact nature and cognitive basis of real world scene perception deficits in PCA remains unclear. Eye‐tracking studies have demonstrated that when viewing a scene that they are slow or unable to recognize, PCA patients' eye movements are initially well‐matched to those of controls, with differences only emerging on later fixations (Mannan, Kennard, & Husain, ; Shakespeare & Crutch, ; see Figure ). This suggests eye movements are initially driven by bottom‐up low‐level features with understanding of the scene and top‐down control subsequently playing a greater role; in PCA, the latter type of process appears more impaired.…”

Section: Cognitive Analysis Of Common and Unusual Symptoms In Pcamentioning

confidence: 99%

“…This apparent discrepancy between the ability to localize target position defined by movement versus static information is mirrored in a number of more recent patients who, despite apparently grave visual disorientation, continue to enjoy preferentially watching certain sports on TV which involve a moving target (e.g., cricket, tennis) or viewing planes in flight at air shows . This discrepancy has been quantified recently using eye‐tracking measures (saccade latency, angle and amplitude) of performance on a single‐point localization task involving a central fixation dot followed by a static or (jittered) moving dot 11˚ from fixation; PCA patients showed significantly lower saccadic angle error in the moving condition (Shakespeare & Crutch, ). The identification of areas of relative visual sparing in PCA may provide the basis for future compensatory strategies and interventions.…”

Section: Cognitive Analysis Of Common and Unusual Symptoms In Pcamentioning

confidence: 99%

“…Another common problem described by PCA patients is that items which are actually static appear to move or jump about when they look at them (e.g., letters within a word; dots on the Dot Counting subtest of the Visual Object and Space Perception [VOSP] battery: Warrington & James, ). Eye‐tracking data suggest this impression may reflect significantly greater instability of fixation control in PCA patients than controls (Crutch et al ., ; Shakespeare & Crutch, ). This fixation instability may be consistent with FDG‐PET evidence showing reduced glucose metabolism in patients with PCA not only in posterior brain regions but also in the frontal eye fields bilaterally (Nestor, Caine, Fryer, Clarke, & Hodges, ).…”

Section: Cognitive Analysis Of Common and Unusual Symptoms In Pcamentioning

confidence: 99%

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Seeing why they cannot see: Understanding the syndrome and causes of posterior cortical atrophy

Crutch

2013

Journal of Neuropsychology

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Posterior cortical atrophy (PCA) is a syndrome defined by focal neurodegeneration of the parietal, occipital, and occipito‐temporal cortices and associated with progressive dysfunction of visual processing, praxis, numeracy and reading. The condition is most commonly caused by (and viewed as an atypical presentation of) Alzheimer's disease, although can also be caused by other degenerative diseases. The current paper examines the relationship of PCA to other degenerative syndromes, and considers what comparisons of these syndromes and disease phenotypes can tell us about underlying disease mechanisms. The focus then turns to neuropsychological investigations of the cognitive basis of symptoms which, although unusual in the broader context of a dementia clinic, are particularly characteristic of the PCA syndrome, before exploring implications for clinical management and patient and carer support.

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“…Une étude pangénomique exploratoire chez 293 patients avec atrophie corticale postérieure suggère l'implication de trois gènes dont deux (SEMA3C et CNTNAP5) qui pourraient contribuer également à des processus en lien avec le développement cérébral [30]. SEMA3C est impliqué dans le développement cortical et hippocampique, ainsi que la maturation du système visuel et CNTNAP5 est associé avec le trouble du spectre de l'autisme, ayant des interactions complexes avec les troubles neurovisuels de l'enfant [26], et la maladie bipolaire, pathologie psychiatrique ayant aussi une forte composante neurodéveloppementale et des lien complexe avec les pathologies neurodégénératives [31].…”

Section: Aphasie Progressive Primaireunclassified

Neurodevelopmental disorders modify neurodegenerative diseases: a medical history to screen in memory clinic

Magnin¹,

Monnin²,

Chokron³

et al. 2021

Gériatrie Et Psychologie Neuropsychiatrie Du Viellissement

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P4‐107: Genetic risk factors for posterior cortical atrophy may be distinct from late‐onset Alzheimer's disease

Cited by 6 publications

References 0 publications

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy

Seeing why they cannot see: Understanding the syndrome and causes of posterior cortical atrophy

Neurodevelopmental disorders modify neurodegenerative diseases: a medical history to screen in memory clinic

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