RARE DISEASE
Posterior cortical atrophy
Posterior cortical atrophy
Posterior cortical atrophy
Synonyms: Benson syndrome, Biparietal Alzheimer disease, PCA
Synonyms: Benson syndrome, Biparietal Alzheimer disease, PCA
Synonyms: Benson syndrome, Biparietal Alzheimer disease, PCA
Drug discovery
0
drugs
With orphan designations
Overview
Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by progressive visuospatial and visuoperceptual deficits due to posterior brain atrophy. Most cases (70–94%) are linked to Alzheimer’s pathology, though Lewy body disease or corticobasal degeneration may also underlie it [1][5][7][12]. Symptoms include simultanagnosia, optic ataxia, alexia, and apraxia, with onset typically between ages 50–65 [2][7][12]. Diagnosis relies on neuroimaging (posterior-predominant atrophy/hypometabolism) and exclusion of ocular pathology [5][10][16].
Therapies
Categories: rare genetic diseases, rare neurological diseases
Research Papers
134 drug discovery papers about Posterior cortical atrophy, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
134 drug discovery papers about Posterior cortical atrophy, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-05 | Eligibility for Anti-Amyloid Therapies in Patients With Biomarker-Confirmed Atypical Alzheimer Disease Phenotypes.
Clinical trials of anti-amyloid therapies (AATs) for Alzheimer disease (AD) primarily enrolled patients with mildly symptomatic, amnestic predominant presentations. The applicability of eligibility criteria to atypical AD phenotypes, including posterior cortical atrophy (PCA), logopenic variant primary progressive aphasia (lvPPA), dysexecutive AD (dAD), and corticobasal syndrome because of AD (CBS-AD), is unknown. We conducted a retrospective eligibility analysis of patients with atypical AD evaluated at Mayo Clinic. Theoretical eligibility for AAT was assessed at initial clinical evaluation by applying inclusion and exclusion criteria from landmark clinical trials (Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease [CLARITY-AD] and the Study of LY3002813 (Donanemab) in Participants With Early Symptomatic Alzheimer's Disease [TRAILBLAZER-ALZ2]) and appropriate use criteria for lecanemab and donanemab. Eligibility percentages and reasons for exclusion were compared across phenotypes. The cohort included 184 patients (61.4% female) with biomarker-confirmed atypical AD: PCA (n = 98, 53.3%), lvPPA (n = 42, 22.8%), dAD (n = 37, 20.1%), and CBS-AD (n = 7, 3.8%). Age at onset (p = 0.039) and presentation (p < 0.001) differed, with patients with lvPPA oldest (median age at onset, presentation: 63.1, 66.9 years) and patients with dAD youngest (onset, presentation: 55.1, 57.3). Functional impairment differed by phenotype (p = 0.005), with lvPPA more often diagnosed at the mild cognitive impairment/very mild stage (Clinical Dementia Rating [CDR] 0.5; 71.4%), whereas PCA and dAD more frequently presented with mild dementia, although time from symptom onset to diagnosis did not differ (p = 0.634). Mini-Mental State Examination (MMSE) scores differed (p = 0.036), with lower scores in PCA and lvPPA (median 21 and 21, respectively) compared with CBS-AD (median 27). Depending on the eligibility framework applied, 70%-85% of patients would not meet treatment criteria. Bedside cognitive thresholds were the primary drivers of ineligibility (50%-67% of exclusions), despite most patients having early symptomatic disease (global CDR 0.5-1; 82%). Imaging-based exclusions (22%-27%) and severity thresholds (moderate or severe dementia, 19%-23%) were also frequent. Reasons for ineligibility were similar across phenotypes. Most patients with atypical AD would not meet eligibility criteria for AAT, typically because of MMSE-based exclusion rather than measures of cognitive function. Eligibility rates are broadly similar across atypical phenotypes. These findings highlight the need for phenotype-sensitive staging and patient selection for treatment in atypical AD.
2026-04-13 | Posterior Cortical Atrophy Presenting with Psychotic Delirium
An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
2026-02-06 | Pharmacological interventions in patients with posterior cortical atrophy: a systematic review
Background: Posterior Cortical Atrophy (PCA) is a rare dementia syndrome, typically caused by an atypical variant of Alzheimer’s disease, and is characterized by progressive visuospatial decline. Cholinesterase inhibitors (AChEIs), used in typical Alzheimer’s disease, are sometimes prescribed for PCA, but evidence supporting their efficacy in this population remains limited. Objective: To summarize current clinical evidence on pharmacological treatments for PCA. Methods: A systematic review was conducted according to PRISMA guidelines. Searches were performed in PubMed, EMBASE, Scopus, and Web of Science for studies published between January 2010 and May 2025. Keywords included “posterior cortical atrophy,” “pharmacological treatment,” and related terms. Studies were excluded if they addressed other causes of cognitive decline, focused solely on non-pharmacological approaches, were case reports, preclinical studies, or lacked full-text access. Results: Only one study met inclusion criteria: a randomized, double-blind, placebo-controlled trial (Ridha et al., 2018) involving 18 PCA patients treated with donepezil. MMSE scores improved significantly at six weeks (difference of 2.5 points; p<0.05), but not at 12 weeks. No improvements were observed in visuospatial tests. Adverse effects were frequent, especially gastrointestinal symptoms (72%) and vivid dreams (44%). Discussion: The study highlighted recruitment challenges and a high rate of side effects, which may have affected blinding. The small sample limits the generalizability of findings. No other neuropsychological outcomes improved. Conclusion: Evidence on pharmacological treatment for PCA is scarce. High-quality clinical trials are needed to guide therapeutic strategies.
2026-01-31 | Alzheimer's Disease Continuum: Evaluating the Relationship between Fluid Biomarkers and Patients' Phenotype and Profile.
The measurement of fluid biomarkers such as phosphorylated tau at threonine 181 (pTAU181), amyloid-β 40 (Aβ40), and Aβ42 is a routine medical examination that contributes to achieving an accurate diagnosis within the Alzheimer's disease (AD) clinical continuum. The aim of this study is to compare the concentration of these biomarkers in CSF and plasma and determine their relationship with the patients' clinical variant and profile. Patients were diagnosed following the NIA-AA criteria. Plasma and CSF were obtained from healthy controls (HC), mild cognitive impairment (MCI non-AD), MCI displaying positive AD markers (MCI-AD), and AD patients. Biomarker levels were assessed using the LUMIPULSE® G600II instrument (Fujirebio, Japan). Data showed a significant increase in pTAU181 concentration, specifically in the progression from MCI non-AD to AD conditions. The opposite trend was observed for Aβ42 and Aβ42/Aβ40. Furthermore, these biomarker trends appeared to change consistently with variations in the MMSE score, highlighting the relevance of plasma in detecting changes in patients' cognitive function. Considering the clinical variant, atypical patients displayed the highest pTAU181 and lowest Aβ42 levels, consistent with their lower MMSE scores. Lastly, the posterior cortical atrophy (PCA) profile showed higher pTAU181 and lower Aβ42 levels when compared to other profiles. Nevertheless, these last results are to be cautiously interpreted given the limited number of samples included in the analysis. Hence, further analyses on larger cohorts are needed to better define the role of these biomarkers in distinguishing between patients' clinical variants.
2025-12-01 | Unravelling Posterior Cortical Atrophy: Clinico‐Imaging Insights from a Tertiary Care Cohort in India
BACKGROUND: Posterior Cortical Atrophy (PCA), first described by Benson et al., is a progressive neurodegenerative disorder affecting visual and posterior cognitive functions, while sparing memory and language in early stages. Although Alzheimer's Disease (AD) pathology underlies most cases, alternative etiologies like Dementia with Lewy Bodies (DLB), Corticobasal Degeneration (CBD), and Prion disease have also been reported. This study examines the clinical, etiological, and imaging profiles of PCA patients evaluated at a tertiary care center in India, using Crutch et al. 2017 consensus criteria. METHOD: Eight PCA patients diagnosed at a tertiary hospital in India between 2021 and 2024 were included in this prospective case series. Demographic data, neuropsychological profiles, imaging findings, and biomarker studies were analyzed. Patients were assessed for visual and posterior cognitive impairments. RESULT: PCA predominantly presented as early-onset cognitive decline in the 5th to 6th decade, with equal gender distribution. All patients exhibited initial visuospatial, visuoperceptual, or praxis impairments. Based on Crutch et al.'s classification, 6 patients (75%) were categorized as Pure PCA, and 2 (25%) as PCA Plus, including PCA-CBS and PCA-AD/DLB mixed. Phenotypically, 3 patients were dorsal variant, 3 ventral, and 2 biparietal. CSF AD biomarkers were positive in 2 Pure PCA patients and 1 PCA-AD/DLB patient. MRI revealed posterior cortical atrophy in all cases. FDG-PET showed parieto-temporo-occipital hypometabolism, with frontal involvement in dorsal/ventral subtypes, while biparietal subtypes showed occipital sparing. Tau-PET in selected cases demonstrated increased uptake in affected regions, matching FDG-PET findings. CONCLUSION: PCA remains underrecognized due to its atypical presentation and early onset. This series highlights the clinical and imaging heterogeneity of PCA in Indian subjects. Advanced imaging, like FDG/Tau-PET, can aid in distinguishing phenotypes. Greater research is needed to explore phenotypic variations, identify biomarkers, and develop targeted therapies.
2026-08-05 | Eligibility for Anti-Amyloid Therapies in Patients With Biomarker-Confirmed Atypical Alzheimer Disease Phenotypes.
Clinical trials of anti-amyloid therapies (AATs) for Alzheimer disease (AD) primarily enrolled patients with mildly symptomatic, amnestic predominant presentations. The applicability of eligibility criteria to atypical AD phenotypes, including posterior cortical atrophy (PCA), logopenic variant primary progressive aphasia (lvPPA), dysexecutive AD (dAD), and corticobasal syndrome because of AD (CBS-AD), is unknown. We conducted a retrospective eligibility analysis of patients with atypical AD evaluated at Mayo Clinic. Theoretical eligibility for AAT was assessed at initial clinical evaluation by applying inclusion and exclusion criteria from landmark clinical trials (Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease [CLARITY-AD] and the Study of LY3002813 (Donanemab) in Participants With Early Symptomatic Alzheimer's Disease [TRAILBLAZER-ALZ2]) and appropriate use criteria for lecanemab and donanemab. Eligibility percentages and reasons for exclusion were compared across phenotypes. The cohort included 184 patients (61.4% female) with biomarker-confirmed atypical AD: PCA (n = 98, 53.3%), lvPPA (n = 42, 22.8%), dAD (n = 37, 20.1%), and CBS-AD (n = 7, 3.8%). Age at onset (p = 0.039) and presentation (p < 0.001) differed, with patients with lvPPA oldest (median age at onset, presentation: 63.1, 66.9 years) and patients with dAD youngest (onset, presentation: 55.1, 57.3). Functional impairment differed by phenotype (p = 0.005), with lvPPA more often diagnosed at the mild cognitive impairment/very mild stage (Clinical Dementia Rating [CDR] 0.5; 71.4%), whereas PCA and dAD more frequently presented with mild dementia, although time from symptom onset to diagnosis did not differ (p = 0.634). Mini-Mental State Examination (MMSE) scores differed (p = 0.036), with lower scores in PCA and lvPPA (median 21 and 21, respectively) compared with CBS-AD (median 27). Depending on the eligibility framework applied, 70%-85% of patients would not meet treatment criteria. Bedside cognitive thresholds were the primary drivers of ineligibility (50%-67% of exclusions), despite most patients having early symptomatic disease (global CDR 0.5-1; 82%). Imaging-based exclusions (22%-27%) and severity thresholds (moderate or severe dementia, 19%-23%) were also frequent. Reasons for ineligibility were similar across phenotypes. Most patients with atypical AD would not meet eligibility criteria for AAT, typically because of MMSE-based exclusion rather than measures of cognitive function. Eligibility rates are broadly similar across atypical phenotypes. These findings highlight the need for phenotype-sensitive staging and patient selection for treatment in atypical AD.
2026-04-13 | Posterior Cortical Atrophy Presenting with Psychotic Delirium
An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
2026-02-06 | Pharmacological interventions in patients with posterior cortical atrophy: a systematic review
Background: Posterior Cortical Atrophy (PCA) is a rare dementia syndrome, typically caused by an atypical variant of Alzheimer’s disease, and is characterized by progressive visuospatial decline. Cholinesterase inhibitors (AChEIs), used in typical Alzheimer’s disease, are sometimes prescribed for PCA, but evidence supporting their efficacy in this population remains limited. Objective: To summarize current clinical evidence on pharmacological treatments for PCA. Methods: A systematic review was conducted according to PRISMA guidelines. Searches were performed in PubMed, EMBASE, Scopus, and Web of Science for studies published between January 2010 and May 2025. Keywords included “posterior cortical atrophy,” “pharmacological treatment,” and related terms. Studies were excluded if they addressed other causes of cognitive decline, focused solely on non-pharmacological approaches, were case reports, preclinical studies, or lacked full-text access. Results: Only one study met inclusion criteria: a randomized, double-blind, placebo-controlled trial (Ridha et al., 2018) involving 18 PCA patients treated with donepezil. MMSE scores improved significantly at six weeks (difference of 2.5 points; p<0.05), but not at 12 weeks. No improvements were observed in visuospatial tests. Adverse effects were frequent, especially gastrointestinal symptoms (72%) and vivid dreams (44%). Discussion: The study highlighted recruitment challenges and a high rate of side effects, which may have affected blinding. The small sample limits the generalizability of findings. No other neuropsychological outcomes improved. Conclusion: Evidence on pharmacological treatment for PCA is scarce. High-quality clinical trials are needed to guide therapeutic strategies.
2026-01-31 | Alzheimer's Disease Continuum: Evaluating the Relationship between Fluid Biomarkers and Patients' Phenotype and Profile.
The measurement of fluid biomarkers such as phosphorylated tau at threonine 181 (pTAU181), amyloid-β 40 (Aβ40), and Aβ42 is a routine medical examination that contributes to achieving an accurate diagnosis within the Alzheimer's disease (AD) clinical continuum. The aim of this study is to compare the concentration of these biomarkers in CSF and plasma and determine their relationship with the patients' clinical variant and profile. Patients were diagnosed following the NIA-AA criteria. Plasma and CSF were obtained from healthy controls (HC), mild cognitive impairment (MCI non-AD), MCI displaying positive AD markers (MCI-AD), and AD patients. Biomarker levels were assessed using the LUMIPULSE® G600II instrument (Fujirebio, Japan). Data showed a significant increase in pTAU181 concentration, specifically in the progression from MCI non-AD to AD conditions. The opposite trend was observed for Aβ42 and Aβ42/Aβ40. Furthermore, these biomarker trends appeared to change consistently with variations in the MMSE score, highlighting the relevance of plasma in detecting changes in patients' cognitive function. Considering the clinical variant, atypical patients displayed the highest pTAU181 and lowest Aβ42 levels, consistent with their lower MMSE scores. Lastly, the posterior cortical atrophy (PCA) profile showed higher pTAU181 and lower Aβ42 levels when compared to other profiles. Nevertheless, these last results are to be cautiously interpreted given the limited number of samples included in the analysis. Hence, further analyses on larger cohorts are needed to better define the role of these biomarkers in distinguishing between patients' clinical variants.
2025-12-01 | Unravelling Posterior Cortical Atrophy: Clinico‐Imaging Insights from a Tertiary Care Cohort in India
BACKGROUND: Posterior Cortical Atrophy (PCA), first described by Benson et al., is a progressive neurodegenerative disorder affecting visual and posterior cognitive functions, while sparing memory and language in early stages. Although Alzheimer's Disease (AD) pathology underlies most cases, alternative etiologies like Dementia with Lewy Bodies (DLB), Corticobasal Degeneration (CBD), and Prion disease have also been reported. This study examines the clinical, etiological, and imaging profiles of PCA patients evaluated at a tertiary care center in India, using Crutch et al. 2017 consensus criteria. METHOD: Eight PCA patients diagnosed at a tertiary hospital in India between 2021 and 2024 were included in this prospective case series. Demographic data, neuropsychological profiles, imaging findings, and biomarker studies were analyzed. Patients were assessed for visual and posterior cognitive impairments. RESULT: PCA predominantly presented as early-onset cognitive decline in the 5th to 6th decade, with equal gender distribution. All patients exhibited initial visuospatial, visuoperceptual, or praxis impairments. Based on Crutch et al.'s classification, 6 patients (75%) were categorized as Pure PCA, and 2 (25%) as PCA Plus, including PCA-CBS and PCA-AD/DLB mixed. Phenotypically, 3 patients were dorsal variant, 3 ventral, and 2 biparietal. CSF AD biomarkers were positive in 2 Pure PCA patients and 1 PCA-AD/DLB patient. MRI revealed posterior cortical atrophy in all cases. FDG-PET showed parieto-temporo-occipital hypometabolism, with frontal involvement in dorsal/ventral subtypes, while biparietal subtypes showed occipital sparing. Tau-PET in selected cases demonstrated increased uptake in affected regions, matching FDG-PET findings. CONCLUSION: PCA remains underrecognized due to its atypical presentation and early onset. This series highlights the clinical and imaging heterogeneity of PCA in Indian subjects. Advanced imaging, like FDG/Tau-PET, can aid in distinguishing phenotypes. Greater research is needed to explore phenotypic variations, identify biomarkers, and develop targeted therapies.
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