Diagnosis Of Posterior Cortical Atrophy Research Articles

Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis

Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid β in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%). These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity. None.

Posterior cortical atrophy in clinical practice

AbstractBackgroundA consensus classification framework for posterior cortical atrophy (PCA) was proposed in 2017 to define the core clinico‐pathological syndrome. Main features include a variety of visuospatial deficits associated with posterior cortex dysfunction, together with predominant posterior cortical atrophy. Additional neurological symptoms may be present in what is termed PCA‐plus. Several proteinopathies could be the underlying neuropathology, though in vivo biomarkers only allow for identification of Alzheimer’s disease (AD).MethodWe described the clinical phenotype and biomarkers in a series of patients diagnosed at our memory clinic of PCA (n = 13). Retrospective review of age at onset, family history, cognitive symptoms, neurological deficits, patterns of brain atrophy in MRI, AD biomarkers in CSF, and available genetic analyses.ResultThere were eight women and five men; five had a family history of dementia (Goldman score 3.5) while eight were apparently sporadic cases. Age at onset of symptoms ranged from 30 to 75 years (median 66) and first neurological consultation was 1 to 2 years later, though both psychiatrists and ophthalmologists had already evaluated 46% of the cases. Diagnosis of PCA was established between 5 months and 5 years (mean 2 years) of first assessment. Brain atrophy was parieto‐occipital in 11 cases and temporo‐parietal in two (bilateral in seven, left predominant in four and right in two). Three cases had a PCA‐plus syndrome, one with parkinsonism an another two with CBD features. Five cases (including one with CBD) had AD CSF biomarkers studied, all with an A+T+N+ pattern. APOE was available in eight cases, five carried ε3/ε3 and three ε3/ε4 alleles. The patient with younger onset carried a PSEN1 pathogenic mutation (p.Pro436Gln). Three cases had C9orf72 expansion and plasma progranulin levels analyzed with negative results. Most cases were dependent for activities of daily living after five years of evolution.ConclusionThis series further contributes to the characterization of the clinical heterogeneity of PCA. Anxiety and depression are common in early stages of the disease. Biomarkers are usually consistent with AD.

Biomarkers of Alzheimer’s disease pathology in atypical non‐amnestic clinical phenotypes

AbstractBackgroundAlzheimer’s disease (AD) is most commonly presented with memory loss features. However, there are atypical clinical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. The goal of our study was to estimate the prevalence of Alzheimer’s pathology in non‐amnestic clinical variants.MethodWe examined 40 patients (17 males, 23 females, 66.1±8.3 yrs) with atypical phenotypes of AD (Table 1). Seven patients had the phenotype of logopenic variant of primary progressive aphasia (lvPPA), 3 patients had the diagnosis of posterior cortical atrophy (PCA), 19 had corticobasal syndrome (CBS), and 11 cases met research criteria of clinical behavioral variant of AD (bvAD). All patients underwent lumbar puncture. CSF biomarkers Abeta‐42 (cutoff 150 pg/mL) and p‐tau181 (cutoff 600 pg/mL) were analyzed. According to the recommendations of International Working Group (2021) we defined probable and possible AD based on clinical phenotype and studied CSF biomarkers.ResultThe overall prevalence of AD pathology in the studied groups was 42.5% (20% for probable diagnosis and 22.5% for possible). All results are presented in Table 1. The highest prevalence of AD pathology in atypical clinical phenotypes was found in the group of PCA (66.7%), the lowest ‐ in the group of bvAD (36.4%). Almost a half of patients in both lvPPA and CBS groups had AD pathology based on biomarkers – 42.9% and 42.2%, respectively.ConclusionThe results showed the importance of verifying AD pathology biomarkers in common (PCA, lvPPA) and uncommon (CBS) phenotypes. Behavioral variant, considered as a rare AD phenotype, in our studied cohort was characterized by relatively high occurrence of positive AD biomarkers. Increasing the use of AD biomarkers in clinical practice and greater recognition of atypical phenotypes can ensure early diagnosis, treatment and care for these patients.

57 Sensitivity of functional Near-Infrared Spectroscopy in Individuals with Posterior Cortical Atrophy

Objective:Functional near infrared spectroscopy (fNIRS) is a form of non-invasive neuroimaging that uses light to measure changes in oxygenated and deoxygenated hemoglobin (Yucel et. al., 2021). Relative to fMRI, fNIRS is significantly cheaper and less susceptible to motion artifacts thereby enabling researchers to acquire data in more ecologically valid environments and has a higher temporal resolution that makes it well-suited for connectivity analyses (Tak and Ye, 2014). fNIRS is, however, uniquely limited by cortical anatomy. With a typical probe array having a penetrance depth of up to 3cm, the benefits of fNIRS may be limited by the neocortical atrophy that is characteristic in those with neurodegeneration. We present preliminary findings comparing fNIRS probe sensitivity in older adults diagnosed with posterior cortical atrophy (PCA) relative to cognitively intact older adults using Monte Carlo (MC) simulations. MC simulations offer probabilistic models that simulate photon movement through tissues of interest. We were particularly interested in fNIRS' sensitivity in the occipitoparietal cortices since these are regions characteristically affected in PCA.Participants and Methods:We acquired high resolution structural (T1) MRI on 3 cognitively intact older adults and 3 individuals who received a clinical diagnosis of PCA according to Crutch et al. (2017) criteria. Individual T1 scans were preprocessed and transformed into a twodimensional (2D) surface using FreeSurfer. This continuous 2D surface was then segmented into its main tissue priors, as well as its pial surfaces. Segmented MRIs were then imported into AtlasViewer software and registered to our full head fNIRS probe array via an affine transformation. We embedded the GPU-accelerated Monte Carlo Extreme 3D light transport simulator software (Fang and Boas, 2009) into AtlasViewer which enabled us to launch 10 million photons from each optode, compared to the 1 million that AtlasViewer is set to by default, thereby providing more accurate results (Aasted et. al., 2015). We then assessed the sensitivity profile (log units), a mathematical estimate of optical density, of the inferior and superior occipital gyri, middle occipital gyrus, the superior and inferior parietal lobules, and left and right precunei.Results:Among the regions interrogated, five channels on our fNIRS probe were markedly different between the controls and those with PCA. Specifically, sensitivity values for channels covering the right inferior (hedges g = 8.04) and left superior occipital gyrus (hedges g = 2.46), the right inferior parietal lobule (hedges g = 8.89), and the right (hedges g = 9.43) and left (hedges g = 14.83) precunei were all markedly lower in those with PCA.Conclusions:We provided preliminary evidence that the sensitivity of fNIRS appears to be markedly reduced in those with PCA. This is especially relevant for researchers using fNIRS in populations with neurodegeneration. Future work will evaluate these findings in a larger sample as well as in other neurologic conditions with the goal of helping researchers appropriately power their studies and interpret their results.

A - 59 Regional Cerebral Metabolism Is Associated with Performance on the Visual Object and Space Perception Battery in those with Posterior Cortical Atrophy.

Posterior cortical atrophy (PCA) is a relatively rare clinical syndrome characterized by visuoperceptual/spatial dysfunction with relatively preserved memory, language, and insight in the early stages. Thus, PCA provides a unique population through which to evaluate structure-function relationships for commonly used neuropsychological tests. Here, we evaluated relationships between fluorodeoxyglucose (FDG) positron emission tomography (PET) and performance on the Visual Object and Space Perception (VOSP) Battery. Ten participants with an established diagnosis of PCA underwent baseline neuropsychological testing that included the VOSP, FDG-PET, and structural MRI. We used FreeSurfer to identify anatomical structures in the structural MRI scans, aligned the MRI and PET scans, and then extracted FDG signal from these same regions. Several brain regions relevant for PCA were a priori targeted. We evaluated relationships between the regional FDG values and VOSP performances using Spearman's rank correlation. Silhouettes, Dot Counting, and Number Location showed strong relationships with the superior parietal lobule bilaterally. The right superior parietal lobule showed moderate to strong relationships with Incomplete Letters and Progressive Silhouettes, whereas the left superior parietal lobule showed a strong relationship with Object Decision. Incomplete letters showed a strong relationship with the right supramarginal gyrus. Silhouettes showed a strong relationship with the left fusiform gyrus. These findings from a relatively rare and heterogeneous syndrome provide insight into the regional contributions to visuospatial functioning. Future work will evaluate network-level integrity with these tasks in order to further clarify structure-function relationships.

Consensus recommendations for clinical assessment tools for the diagnosis of posterior cortical atrophy syndrome from the Atypical AD PIA of ISTAART

AbstractINTRODUCTIONDelay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed.METHODSRecommendations were developed using results from a web‐based survey of members of Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Atypical Alzheimer's Disease Professional Interest Area (PIA), literature review, and consensus by the PCA assessment working party of the Atypical Alzheimer's Disease PIA.RESULTSSurvey results revealed robust agreement for assessment tool preferences for PCA features, and many respondents indicated that they reserve assessment tools for use only when PCA is suspected. For some PCA features, curated tools were preferred over validated battery tools, particularly for the office visit. Consensus recommendations superseded survey preferences for two core cognitive features within the 2017 PCA diagnostic criteria.DISCUSSIONThese consensus recommendations provide an evaluation framework for PCA clinical features and can facilitate timely and accurate recognition and diagnosis of PCA. Broader use of these tools should be sought, and development and validation of novel PCA clinical outcome assessments are needed to improve our understanding of atypical AD and other dementias and support the inclusion of those with PCA in treatment trials.

A Novel PSEN1 Variant Leading to Posterior Cortical Atrophy: A Case Report.

We describe a 52-year-old patient with a progressive visuospatial disorder and apraxia. Neuropsychological assessment, neuroradiological findings, and Alzheimer's disease (AD) core biomarker assay on cerebrospinal fluid led to a diagnosis of posterior cortical atrophy due to AD. We performed a next generation sequencing dementia-gene panel and found the c.1301 C>T p.(Ala434Val) variant in the Presenilin1 (PSEN1) gene. The missense change affects the PAL (Pro433-Ala434-Leu435) motif critical for catalytic activity of the macromolecular γ-secretase complex. Evolutionary and integrated bioinformatic tools predicted a deleterious effect of the variant supporting its role in the AD pathogenesis.

A-117 Posterior Cortical Atrophy Case Study: Neuropsychological Assessment Remains Gold Standard Diagnostic Tool of Choice

Abstract Objective: Posterior cortical atrophy (PCA) is a rare, early onset, neurodegenerative syndrome that is characterized by impaired visuospatial/visual-constructional skills. Patients describe vague visual symptoms; however, ocular assessments are usually normal. Alzheimer's disease is the most common underlying cause of PCA; however, brain MRI is often unrevealing early in the disease. As a result, accurate diagnosis is often delayed. Method: The patient was initially referred in 2016 for a concussion evaluation following a work-related head injury when she was 54. Initial MRI of the brain was unremarkable. Neuropsychological testing was repeated in 2019, which was the first diagnostic test to establish a diagnosis of PCA. Subsequently, MRI of the brain with volumetric analysis showed total hippocampal volume to be at the 99th percentile and no pattern of cerebral volume loss to suggest a specific diagnosis. However, CSF biomarker assays were consistent with a diagnosis of Alzheimer’s disease. Results: The patient’s initial cognitive profile in 2016 reflected mild cognitive impairment, multidomain type with severely impaired visual-constructional skills, which were unrelated to her concussion. Neuropsychological testing was repeated in 2019, which showed interval progressive cognitive and functional decline. Profound visual-constructional impairments were again noted (see image), and she met criteria for PCA. Neuropsychological testing was repeated in 2021 and showed progression to moderate dementia with features of Gerstmann's syndrome. Conclusions: In spite of sophisticated neuroimaging techniques and increasing access to CSF biomarker analysis, neuropsychological assessment remains the gold standard diagnostic tool of choice for neurologists faced with rare dementia syndromes, such as PCA. See patient video at: https://youtu.be/9HdAKSL5alg

Posterior Cortical Atrophy phenotype in a GBA N370S mutation carrier: a case report

BackgroundGlucocerebrosidase (GBA) heterozygous variants are the most important genetic risk factor for the development of alpha-synucleinopathies (i.e., Parkinson’s disease and Dementia with Lewy Bodies). Herein, we report for the first time on a patient with a clinical diagnosis of Posterior Cortical Atrophy, carrier of the common GBA heterozygous variant N370S (c.1226A > G).Case presentationA 44-year-old woman with positive familial history for Dementia with Lewy Bodies disclosed three related signs characterizing the Balint’s syndrome: ocular apraxia, optic ataxia and simultanagnosia. Over 2-year follow up, overt gaze apraxia (psychic paralysis of gaze) appeared leading to functional blindness. Given her young age at onset and positive familial history, she underwent a next-generation-sequencing (NGS) based screening of a panel of 32 genes related to neurodegenerative conditions within the ANAMNESYS (An origiNal Approach to study faMiliarity in NEurodegenerative SYndromeS) study. NGS demonstrated the N370S variant in the GBA gene (rs76763715), confirmed by Sanger sequencing. This is a relatively common variant, with predicted mild impact, already reported to occur in 2.4% of PD Italian patients; however, neither this nor other GBA variants have ever been reported to date in patients with Posterior Cortical Atrophy. Glucocerebrosidase activity was investigated and found to be significantly reduced (4.72 nmol/h/mg) compared to healthy controls as well as patients affected by neurodegenerative diseases, further supporting pathogenicity of the GBA variant.ConclusionsWe report on a patient with a clinical diagnosis of Posterior Cortical Atrophy, carrier of the GBA heterozygous variant N370S (c.1226A > G; p.Asn409Ser) determining reduced GCase activity. This report also confirms the role of NGS-based targeted gene analysis in detecting peculiar clinical phenotypes associated with known pathogenic mutations and reinforces the knowledge that carriers of genetic variants often present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria in defining boundaries between distinct conditions and the difficulties of clinicians in reaching the best clinical diagnosis.

Posterior cortical atrophy – a challenge for ophthalmologists

Posterior cortical atrophy (PCA) is a neurodegenerative clinical-radiological condition with atrophy of the posterior portions of the cerebral cortex, including the visual cortex and portions of the parietal and temporal cortex. Nonspecific visual disorders are often misinterpreted as ophthalmological leading to a delayed true diagnosis. Differentiating PCA from other diseases can be demanding and time-consuming. A patient with PCA at the age of 57 is shown presenting visual perceptual disorders for years, initially diagnosed as ophthalmic diseases and then as unexplained visual impairment. A radial keratotomy was performed 25 years ago, and six years ago a phakic intraocular verisyse lens was implanted. No suspected optical neuropathy or maculopathy was confirmed during neuroophthalmological observation. Careful medical history reveals that the family noted the patient’s facial recognition, reading and writing difficulties years earlier. The difficulties of estimating depth and spatial orientation, problems with stairs especially when descending were noted. A large discrepancy was found between the reported functional visual impairments (visual acuity, visual field, Ishihara color test) on the one hand, and on the other hand a normal ophthalmoscopic examination on the retina and a normal morphological finding on OCT (Optical Coherence Tomography). The MRI scan also raised suspicion of cortical problems and the patient was directed to further neurological and neuro-radiological observation with PET-FDG leading to the diagnosis of PCA. PCA is an important condition, since these patients usually refer first to ophthalmologists because of visual impairment. Due to normal finding on ophthalmoscopy and normal OCT, they are considered as patients with unexplained visual loss, which is not appropriate. In these cases cortical cause of visual impairment should be considered. Therefore, history data or medical history should be obtained. Sometimes, gathering of comprehensive data pertainingto past and present medical condition from the family members is needed. A specialist in cognitive neurologyshould also be consulted. The aim of this paper is to raise the awareness of physicians about this entity as a possible cause of unexplained vision loss, and to facilitate early recognition with appropriate diagnostic methods.

Update on posterior cortical atrophy.

Non-amnestic (or atypical) presentations of neurodegenerative dementias are underrecognized and underdiagnosed, including posterior cortical atrophy (PCA) syndrome, which is characterized by prominent visuospatial and visuoperceptual dysfunction at presentation. It is most commonly due to Alzheimer's disease pathology, while Lewy body disease, corticobasal degeneration, and prion disease are neuropathological entities that are less frequently associated with PCA. The diagnosis of PCA is often delayed, to the detriment of the patient, and awareness and understanding of PCA will improve detection, prognostication, and treatment. The natural history of PCA appears to be distinct from typical Alzheimer's disease and significant heterogeneity exists within the PCA syndrome, with the underlying causes of this heterogeneity beginning to be explored. Functional and molecular imaging can assist in better understanding PCA, particularly assessment of network disruptions that contribute to clinical phenotypes. Cerebrospinal fluid biomarkers are useful to detect underlying pathology, but measures of retinal thickness are less promising. There are currently no adequate treatment options for PCA. Continued efforts to characterize PCA are needed, and greater awareness and understanding of atypical presentations of neurodegenerative dementias could serve to elucidate pathobiological mechanisms of underlying disease.

NEUROPSYCHOLOGICAL ASSESSMENT OF POSTERIOR CORTICAL ATROPHY: A CASE STUDY

The following case study examines the presentation of Mr. Fraser*, an older adult African American male diagnosed with Posterior Cortical Atrophy (PCA) following neuropsychological evaluation. PCA is a rare variant of Alzheimer’s Disease (AD) that results in visuospatial and perceptual deficits. Unlike other forms of neurocognitive degeneration, PCA tends to present at a relatively young age and may progress rapidly. There is currently a lack of studies examining PCA from a neuropsychological perspective, which may contribute to low awareness of this condition, as well as delayed diagnosis. It has been estimated that approximately 5% of patients with AD exhibit the PCA variant, implying that this a rare but serious condition. The following case study focuses on Mr. Fraser, a 65-year-old who was referred for neuropsychological assessment to assess his cognitive functioning. Mr. Fraser was administered a comprehensive assessment battery, and his overall results were suggestive of severe deficits in delayed memory and visuospatial skills. In the case of Mr. Fraser, these observed deficits, along with identification of visual complaints noted by his geriatrician, ultimately led to a diagnosis of PCA. While this was supported by neurological testing, the DSM-5 does not currently recognize PCA as a diagnosis. As a result, Mr. Fraser was given a diagnosis of possible AD with potential PCA, which may contribute to underestimates of the prevalence of this disorder. Future research and practice should focus on common neuropsychological presentations of this condition. *Identifying information changed in accordance with HIPAA guidelines

Posterior Cortical Atrophy: Does Complaint Match the Impairment? A Neuropsychological and FDG-PET Study.

Objective: Posterior Cortical Atrophy (PCA) is a neurodegenerative disease characterized predominantly by visual impairment. However, diagnosis of PCA remains complicated with an interval of several years between initial reporting of symptoms and diagnosis. The aim of the present study is to define if patients' visual and gestural complaints are consistent with their clinical profile.Method: An evaluation of daily visual problems as well as a full neuropsychological assessment and FDG-PET were performed in 15 PCA patients. We compared glucose metabolism between these PCA patients and 18 healthy controls. Correlation analyses were conducted in PCA patients between visual and gestural complaint, clinical impairments, and brain glucose metabolism.Results: Major impairment of cognitive functions was detected in PCA patients specifically in visual domains. Positive correlations were found between visual impairments and hypometabolism in the right temporo-parieto-occipital cortices. However, no correlation was found between complaint and visual impairment in PCA patients.Discussion: Our main results suggest a consistent relationship between clinical impairment and brain metabolism. However, the patient's complaint and visual performance are not linked. Combining the literature and our results, it seems that patients are generally aware of difficulties but misinterpret them. This misinterpretation may be responsible for the delayed diagnosis.

AGR - 2 Diagnosis of Posterior Cortical Atrophy Through Inter-Departmental Collaboration

Abstract Objective We present a patient with rapidly progressive visual decline of 2-year duration that interfered with daily functioning. She was evaluated by neuro-ophthalmology and neurology prior to neuropsychological referral. A series of evaluations led to diagnosis of posterior cortical atrophy, demonstrating the importance of inter-departmental collaboration. Method A 66-year old white female presented with a 2-year history of progressive changes to vision and memory. Medical history included hypertension, dyslipidemia, and a strong family history of optic neuropathy causing blindness. She was diagnosed with a left homonymous hemianopia. MRI revealed "significant cortical atrophy more remarkable on the right temporal, parietal, and occipital regions." She reported dressing apraxia, unsteady gait, declines in reading and writing, and difficulty recalling well-learned information. Results She was a good historian, had fluent speech and no apparent comprehension difficulty. Neuropsychological evaluation revealed relatively preserved language and verbal abilities, including confrontation naming, in the presence of otherwise impaired performances across all domains of functioning. She demonstrated agraphia, acalculia, left-right confusion, and difficulties with motor programming. Perceptual and constructional tasks revealed prominent deficits in visual integration, map orientation, form discrimination, and construction of simple geometric designs. She was perseverative and susceptible to verbal and visual stimulus pull. Conclusions The pattern on neuropsychological testing, with prominent visual spatial and perceptual difficulties, was consistent with posterior cortical atrophy. The decline in visual ability is likely exacerbated but not entirely explained by left hemianopia. Neuropsychological, neuroimaging, and visual field evidence demonstrated posterior cortical atrophy in the absence of positive biomarker evidence, leading to initiation of anti-cholinesterase therapy.

‘Because my brain isn’t as active as it should be, my eyes don’t always see’: a qualitative exploration of the stress process for those living with posterior cortical atrophy

ObjectivesTo explore the stress process for individuals living with posterior cortical atrophy (PCA) and their families.DesignA qualitative study using in-depth semi-structured dyadic and individual interviews with people living with a...

Lateral parietal contributions to memory impairment in posterior cortical atrophy.

ObjectivePosterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive impairment in visuospatial and perceptual function. Recent findings show that memory functioning can also be compromised early in the course of disease. In this study, we investigated the neural basis of memory impairment in PCA, and hypothesised that correlations would be observed with parietal cortex rather than classic medial temporal memory structures.MethodsEighteen PCA patients, 15 typical Alzheimer's disease (tAD) patients and 21 healthy controls underwent memory testing with the Rey Auditory Verbal Learning Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to identify regions in the parietal and medial temporal lobes that correlated with memory performance.ResultsCompared with controls, PCA patients were impaired at learning, immediate and delayed recall and recognition of the RAVLT. Learning rate and immediate recall was significantly better in PCA compared to tAD, whereas there was no difference in delayed recall. Recognition memory also was not statistically different between patient groups, but PCA patients made significantly more false positive errors than tAD patients. VBM analysis in the PCA patients revealed a significant correlation between total learning and grey matter density in the right supramarginal gyrus, right angular gyrus and left postcentral gyrus. The left post central gyrus also significantly correlated with immediate and delayed recall and with recognition memory. No correlations were detected in the medial temporal lobe.ConclusionsThe findings provide novel evidence that early verbal memory impairment is frequently observed in PCA, and is associated with damage to lateral parietal structures. The results have implications for the diagnosis and management of PCA.

Can patients without early, prominent visual deficits still be diagnosed of posterior cortical atrophy?

BackgroundEarly and progressive disabling visual impairment is a core feature for the diagnosis of posterior cortical atrophy (PCA). However, some individuals that fulfil criteria over time might initially present with an onset of prominent posterior dysfunction other than visuoperceptual. MethodsThe clinical profile of five patients with a predominantly ‘non-visual’ posterior presentation (PCA2) was investigated and compared with sixteen individuals with visually predominant PCA (PCA1) and eighteen with typical amnestic Alzheimer disease (tAD). ResultsPCA2 patients showed significantly better performance than PCA1 in one visuospatial task and were free of Balint's syndrome and visual agnosia. Compared to tAD, PCA2 showed trends towards significantly lower performance in visuoperceptual tasks, more severe apraxia and more symptoms of Gerstmann's syndrome. ConclusionsOur sample of PCA2 patients did not present with clinically prominent visual symptoms but did show visual dysfunction on formal neuropsychological assessment (less pronounced than in PCA1 but more than in tAD) in addition to other posterior deficits. Broadening the definition of PCA to encompass individuals presenting with prominent ‘non-visual’ posterior dysfunction should be potentially considered in clinical and research contexts.

Diagnostic value of 18F-FDG PET and 11C-PIB PET on early stage posterior cortical atrophy

Background Posterior cortical atrophy (PCA) is a kind of progressive neurodegenerative disease with cortical visual impairment as the first symptom. Because of rare clinical incidence, early onset age, special clinical symptoms and unobvious MRI abnormality, the definitive diagnosis of PCA is difficult. This study used 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET and 11 C-Pittsburgh compound B ( 11 C-PIB) PET for PCA patients with unobvious MRI abnormality, so as to discuss the value of PET in the early diagnosis of PCA. Methods Five patients diagnosed as PCA in our hospital between April 2012 and March 2015 were enrolled in this study. Cognitive function was measured by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) and Clock Drawing Test (CDT). Brain MRI, 18 F-FDG PET and 11 C-PIB PET were performed to analyze glucose metabolism and perfusion of posterior cortex. Results Neuropsychological tests revealed that the ability of writing, calculating, visuospatial and executive function of all these patients were impaired. Color vision tests showed abnormal results. MRI showed that the posterior atrophy (PA) scores were 0-2 (average 1) on the left side and 0-1 (average 0.80) on the right side. The medial temporal atrophy (MTA) scores were 1-3 (average 1.80) on the left side and 1-4 (average 2) on the right side. The ventricular enlargement (VE) scores were 1-2 (average 1.80) on the left side and 1-2 (average 1.60) on the right side. 18 F-FDG PET showed glucose metabolism decreased obviously on bilateral temporo-parieto-occipital cortex, precuneus and cingulate gyrus, and slightly on frontal lobes and subcortical structure. 11 C-PIB PET showed radioactive 11 C-PIB deposition on bilateral frontal, temporal, parietal and occipital cortex, and the outline of cerebellar cortex was clear. Conclusions For PCA patients whose parietal and occipital cortical atrophy is not obvious on MRI, 18 F-FDG PET combined with 11 C-PIB PET plays an important role in early diagnosis. DOI: 10.3969/j.issn.1672-6731.2015.08.005

Lewy Body Dementia as an Underlying Etiology for Posterior Cortical Atrophy Initially Presented with Visual Agnosia and Alexia: A Case Report

Posterior cortical atrophy (PCA) is a neurodegenerative disorder with cerebral atrophy in the parietal, occipital, or occipitotemporal cortices, and is characterized by visuospatial and visuoperceptual impairments. The majority of the disorder is compatible pathologically with Alzheimer’s disease (AD). However, many patients show no memory loss until late stages of the disease. We encountered a case where a combination of several imaging modalities, in conjunction with symptoms and neuropsychological exams, led not only to a diagnosis of PCA but also identified its underlying etiology. A 62-year-old Japanese man presented to ophthalmology with visual impairment and without abnormalities in his visual acuity or visual fields. Alexia was identified, particularly pertinent to reading Kanji, at the neurology clinic. His initial Mini-Mental State Examination (MMSE) revealed a score of 27/30 points with delayed recall (-2) and constructional apraxia (-1). The score dropped to 25 points six months later. Brain MRI demonstrated occipital atrophy. Brain single photon emission computed tomography (SPECT) showed hypoperfusion in the medial and lateral occipital lobes. The myocardial meta-iodobenzylguanidine (MIBG) scintigraphy showed no evidence of myocardial postganglionic sympathetic dysfunction. Posterior cortical atrophy (PCA) was diagnosed in conjunction with the symptoms, including alexia and visual impairment. He developed symmetric parkinsonism one year later. Lewy body dementia (DLB) was thus considered as the underlying etiology for the PCA. Additionally, alexia pertinent to reading Kanji has not been reported before. We herein report this rare case.

A 58-year-old female with blurred vision and apraxia

A 58-year-old right handed woman, with 12 years of formal education, had a five-year history of slowly progressive blurred vision and apraxia. Five years before the examination she gradually became blurred vision and had difficulties identifying static objects within the visual field. Then she went to an ophthalmologist and received cataract surgery. However, the symptoms were not improved after surgery. Two years later, she had difficulty doing household chores and was unable to dress herself. She developed an anxiety disorder in the absence of prominent language or memory deficits. Five years after onset, she showed global cognitive decline and abilities of daily life decline. On neurological examination she was alert. Neuropsychological testing revealed a mini-mental state examination (MMSE) score of 20/30 with anomia, agraphia, alexia and partial impairment on time orientation. Biochemical investigations for disorders involving thyroid function, vitamin B 12 , and folate were unremarkable. A brain MRI showed diffuse cortical atrophy and hippocampus atrophy. An 18 F-FDG PET scan showed bilateral hypometabolism at the frontal lobes, tempoparietooccipital adjunction, posterior cingulate cortices and precuneus, insular lobes, caudate nuclei and right thalamus. An 11 C-PIB PET scan showed bilateral amyloid deposits at bilateral frontal lobes and occipital lobes, left temporal lobe and insular, basal ganglia, bilateral cingulate cortices and precuneus. No PSEN1, PSEN2 or APP mutations were identified. This early-onset patient had an unusual cognitive complaint, including visual agnosia and apraxia. The clinical features, structural and functional imaging findings of this case were compatible with the diagnosis of Posterior Cortical Atrophy (PCA). PCA is a neurodegenerative condition characterized by a progressive, often dramatic and relatively selective decline in visual processing skills and other functions subserved by parietal, occipital and occipito-temporal regions, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Often considered as an atypical or variant form of Alzheimer’s disease (AD), PCA typically presents in the mid-50s or early 60s with a variety of unusual symptoms, such as difficulty in interpreting, locating, or reaching for objects under visual guidance or difficulty in navigating. Understanding numbers and reading and writing or spelling may also be affected and, as the disease progresses, patients often develop a more diffuse pattern of cognitive dysfunction, ultimately leading to dementia. The vast majority (>80%) of PCA patients are found to have AD pathology as the cause of dementia at autopsy. Both PCA and AD patients show a similar pattern of high cortical binding on amyloid positron emission tomography (PET) imaging, and analogous changes in cerebrospinal fluid (CSF) level of Aβ42, total tau, and phosphorylated tau. PCA and AD show overlapping atrophy and hypometabolism/hypoperfusion in temporoparietal regions, suggesting a common anatomic focus of neurodegeneration. Structural neuroimaging with either MRI or CT initially shows greater atrophy of visual processing areas in parietotemporo-occipital cortex and relative sparing of critical memory regions in the medial temporal lobe. Over time, the neuroimaging profile of PCA may also merge with that of typical AD. This patient has five-year history of blurred vision and apraxia. At the time of examination, she has been in the stage of global cognitive declining. Diffuse cortical atrophy and hippocampus atrophy in MRI is very difficult to distinguish from typical AD. Hypometabolism and amyloid deposits from PET scan also showed overlapping with typical AD. doi: 10.3969/j.issn.1672-6731.2014.07.018