Lateral parietal contributions to memory impairment in posterior cortical atrophy

Ahmed, Samrah; Loane, Clare; Bartels, Sara Laureen; Zamboni, Giovanna; Mackay, Clare E.; Baker, Ian; Thompson, Sian; Hornberger, Michael; Butler, Chris

doi:10.1016/j.nicl.2018.07.005

Cited by 29 publications

(33 citation statements)

References 51 publications

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“…We found that individuals for whom the majority of their atrophy was specific to limbic regions had worse memory, executive and language scores compared to those for whom the majority of the atrophy took place in the extra-limbic factors. It has been reported in a previous study that performance on verbal learning is associated with volume of the inferior parietal lobules in posterior cortical atrophy (Ahmed et al, 2018), rather than the medial temporal lobe, which contrasts with our findings. However, individuals with atrophy that predominantly affected the limbic regions also showed worse global cognition, indicating that disproportionate limbic atrophy indicates worse cognition overall.…”

Section: Clinical and Neurobiological Heterogeneity Within The Spectrcontrasting

confidence: 99%

Data-driven detection of latent atrophy factors related to phenotypical variants of posterior cortical atrophy

Groot

Yeo

Vogel

et al. 2019

Preprint

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Posterior cortical atrophy is a clinical-radiological syndrome characterized by visual processing deficits and atrophy in posterior parts of the brain, most often caused by Alzheimer's disease pathology. Recent consensus criteria describe four distinct phenotypical variants of posterior cortical atrophy defined by clinical and radiological features; i) object perception/occipitotemporal (ventral), ii) space perception/temporoparietal (dorsal), iii) nonvisual/dominant parietal and iv) primary visual (caudal). We employed a data-driven approach to identify atrophy factors related to these proposed variants in a multi-center cohort of 119 individuals with posterior cortical atrophy (age: 64 SD 7, 38% male, MMSE: 21 SD 5, 71% amyloid-β positive, 29% amyloid-β status unknown). A Bayesian modelling framework based on latent Dirichlet allocation was used to compute four latent atrophy factors in accordance with the four proposed variants. The model uses standardized gray matter density images as input (adjusted for age, sex, intracranial volume, field strength and whole-brain gray matter volume) and provides voxelwise probabilistic maps for all atrophy factors, allowing every individual to express each factor to a degree without a priori classification. The model revealed four distinct yet partially overlapping atrophy factors; right-dorsal, right-ventral, left-ventral, and limbic. Individual participant profiles revealed that the vast majority of participants expressed multiple factors, rather than predominantly expressing a single factor. To assess the relationship between atrophy factors and cognition, neuropsychological test scores covering four posterior cortical atrophy-specific cognitive domains were assessed (object perception, space perception, non-visual parietal functions and primary visual processing) and we used general linear models to examine the association between atrophy factor expression and cognition. We found that object perception and primary visual processing were associated with atrophy that predominantly reflects the rightventral factor. Furthermore, space perception was associated with atrophy that predominantly represents the right-ventral and right-dorsal factors. Similar to the atrophy factors, most participants had mixed clinical profiles with impairments across multiple domains. However, when selecting four participants with an isolated impairment, we observed atrophy patterns and factor expressions that were largely in accordance with the hypothesized variants. Taken together, our results indicate that variants of posterior cortical atrophy exist but these constitute phenotypical extremes and most individuals fall along a broad clinical-radiological spectrum, indicating that classification into four mutually exclusive variants is unlikely to be clinically useful.

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Section: Clinical and Neurobiological Heterogeneity Within The Spectrcontrasting

confidence: 99%

Data-driven detection of latent atrophy factors related to phenotypical variants of posterior cortical atrophy

Groot

Yeo

Vogel

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Though defined by the salient visual impairment, a recent consensus framework highlights the need for clarity on episodic memory impairments(Crutch et al, 2017). Such impairments are noted in the majority of cases at initial clinical assessment (Crutch et al, 2017), and we have previously provided objective evidence for the frequency of episodic memory impairments early in PCA (Ahmed et al, 2016; Ahmed et al, 2018). Our study showed deficits in encoding and retrieval of verbal information at clinical presentation, equivalent to those seen in typical amnestic AD (Ahmed et al, 2016; Ahmed et al, 2018).…”

Section: Introductionmentioning

confidence: 74%

“…Such impairments are noted in the majority of cases at initial clinical assessment (Crutch et al, 2017), and we have previously provided objective evidence for the frequency of episodic memory impairments early in PCA (Ahmed et al, 2016; Ahmed et al, 2018). Our study showed deficits in encoding and retrieval of verbal information at clinical presentation, equivalent to those seen in typical amnestic AD (Ahmed et al, 2016; Ahmed et al, 2018). In support, a recent examination of verbal episodic memory function found evidence of impairment in 65% of PCA patients (Putcha et al, 2018).…”

Section: Introductionmentioning

confidence: 74%

Attention network dysfunction underlies memory impairment in posterior cortical atrophy

Veldsman

Zamboni

Butler

et al. 2019

NeuroImage: Clinical

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Accumulating evidence suggests that memory is impaired in posterior cortical atrophy (PCA), alongside the early and defining visual disorder. The posterior parietal cortex is a key region of pathology in PCA and memory impairment may be the result of dysfunction of parietally dependent network function rather than the medial temporal lobe dependent dysfunction that defines the storage deficits in typical Alzheimer's disease. We assessed episodic memory performance and network function in16 PCA patients and 19 healthy controls who underwent structural and resting-state functional MRI and neuropsychological testing. Memory was assessed using the Free and Cued Selective Reminding Test (FCSRT), a sensitive test of episodic memory storage and retrieval. We examined correlations between memory performance and functional connectivity in the dorsal attention (DAN) and default mode network (DMN). Immediate recall on the FCSRT was relatively preserved in PCA patients. Total recall performance was impaired in patients relative to healthy controls and performance benefitted from retrieval cues. In patients only, disrupted connectivity in the DAN, but not the DMN, was associated with total recall. Memory impairment may arise from disruption to the dorsal attention network, subserved by the dorsal posterior parietal cortex, a key region of pathology in PCA, rather than classic medial temporal lobe memory circuitry.We propose that functional dysconnectivity in attentional circuits underpins memory impairment in PCA.

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“…Memory scores and, in particular, attention/orientation were predictive of overall DAD score. We have recently demonstrated that attention and memory may be impaired early on in PCA [19-21], perhaps related to the crucial role of the parietal lobes in these cognitive functions. Such cognitive changes would intuitively interfere with a person’s ability to undertake everyday tasks.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Pronounced Impairment of Activities of Daily Living in Posterior Cortical Atrophy

Ahmed

Culley

Blanco‐Duque

et al. 2020

Dement Geriatr Cogn Disord

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Introduction: The impact of several dementia syndromes on activities of daily living (ADLs) has been well documented, but no study has yet investigated functional ability in posterior cortical atrophy (PCA). The primarily visual nature of deficits in this condition is likely to have a pronounced impact on ADLs. Objective: The aim of this study was to profile functional change in PCA and identify predictors of change. Method: Twenty-nine PCA patients and 25 patients with typical Alzheimer's disease (AD) and their caregivers were included in this cross-sectional study. ADLs were assessed using the Disability Assessment for Dementia (DAD), administered to caregivers, assessing basic ADLs (e.g., eating, dressing) and instrumental ADLs (e.g., managing finances, meal preparation). The predictive utility of cognitive domains (Addenbrooke's Cognitive Examination), behavioural impairment (Cambridge Behavioural Inventory-Revised) and demographic variables on ADL ability was also examined. Results: PCA patients showed significantly reduced total ADL scores compared to AD patients (medium effect size, d =-0.7; p < 0.05), with significantly more impairment on basic ADLs (large effect size, d =-0.8; p < 0.05) but similar impairment on instrumental ADLs (medium effect size, d =-0.5; p > 0.05). A model combining patient mood, disinhibition, apathy, symptom duration, and memory and attention/orientation scores explained the variance of scores in functional decline (61.2%), but the key factor predicting ADL scores was attention/orientation (p = 0.048). Conclusion: This study shows the profound impact of PCA on ADLs and factors underpinning patients' disability. Attention/orientation deficits were found to correlate and contribute to variance in ADL scores. Future work to develop tailored interventions to manage ADL impairment in PCA should take these findings into account.

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Lateral parietal contributions to memory impairment in posterior cortical atrophy

Cited by 29 publications

References 51 publications

Data-driven detection of latent atrophy factors related to phenotypical variants of posterior cortical atrophy

Data-driven detection of latent atrophy factors related to phenotypical variants of posterior cortical atrophy

Attention network dysfunction underlies memory impairment in posterior cortical atrophy

Pronounced Impairment of Activities of Daily Living in Posterior Cortical Atrophy

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