Visuoconstructional Abilities of Patients With Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Via the Vienna Visuoconstructional Test 3.0 (VVT 3.0) delayed recall we combined the assessment of visuoconstructive abilities and memory and investigated the test's potential to support diagnostic processes, including staging and the elaboration of a cognitive profile. METHODS: We retrospectively analysed the data of 368 patients of the Department of Neurology, Medical University of Vienna, between 04/2014 and 10/2020 that had performed the VVT 3.0. Our sample involved 70 healthy controls (HC), 29 patients with subjective cognitive decline (SCD), 154 patients with mild cognitive impairment (MCI) and 115 patients with Alzheimer's disease (AD). We investigated the differences in the VVT 3.0 scores, as well as the VVT's ability to differentiate between AD and nonAD by calculating receiver-operating-characteristic (ROC) curves, ideal cut-offs and a logistic regression model. RESULTS: Results stated that the VVT 3.0 delayed recall scores were able to differentiate between all diagnostic groups, respectively, except HC-SCD and SCD-MCI. The ROC analyses determined an AUC of 0.890, 95% CI [0.855; 0.925], P < .001, and the ideal cut-off at 29.5 points that maximised sensitivity at 0.896 and specificity at 0.81. The logistic regression model classified 83.4% of AD patients correctly and delivered a significant Cohen's Kappa of 0.619 (P < .001). CONCLUSION: As the VVT 3.0 revealed satisfactory values of diagnostic accuracy in our sample, it could enrich clinical diagnosing. However, for more clarity about its informative value in other populations, there remains a need for future studies with other samples.

The Test of Visuospatial Construction: A Novel Test of Non-motoric Visuoconstruction.

OBJECTIVE: The Test of Visuospatial Construction (TVSC) was designed as an easily administered measure of non-motor visuoconstruction, though only preliminary data exists regarding the clinical utility of this task. The current study examined the diagnostic accuracy of the TVSC by comparing performance between healthy subjects and various clinical groups. The authors also wanted to determine whether previous findings could be replicated regarding its effectiveness at tracking cognitive decline. METHOD: Archival data collected over a period of more than 10 years were utilized and the overall sample consisted of 955 individuals, 372 healthy subjects, and 583 subjects who were categorized into various clinical groups. Only TVSC test data and demographic variables were utilized for statistical analyses in this study. RESULTS: The control group obtained significantly higher scores on the TVSC than the clinical groups. AUC values were indicative of excellent discrimination between cases and controls. Exploratory ROC curve analyses suggested adequate to excellent discrimination between the control group and the individual clinical groups as well as between the mild cognitive impairment (MCI) subgroups and the two dementia groups. CONCLUSIONS: This study demonstrates that the TVSC can effectively differentiate between healthy subjects and neurologically compromised individuals. Additionally, the TVSC may be able to measure the progressive decline in visuoconstructive abilities that occurs as patients traverse the spectrum of MCI and dementia.

Validity of Visuoconstructional Assessment Methods within Healthy Elderly Greek Australians: Quantitative and Error Analysis.

AIMS: Visuospatial skills are frequently assessed with drawing tests. Research has suggested that the use of drawing tasks in low educated groups may lack the ability to discriminate healthy individuals from clinical populations. The aims of this study were to investigate the validity of visuoconstructional tests in a sample of older Greek Australian immigrants and compare their performances to a matched sample of patients with Alzheimer's disease (ad). METHOD: We assessed visuoconstructional performances in a sample of 90 healthy older Greek Australians, with a primary school level of education, and compared performances to a demographically matched sample of 20 Greek Australians with a diagnosis of ad on four visuoconstructional drawing tests: Greek cross, four-pointed star, intersecting pentagons, and the Necker Cube. RESULTS: While healthy participants tended to outperform the ad group on most copy tasks, high fail rates within the healthy sample were observed for the intersecting pentagons and Necker cube (78% and 73% fail rates, respectively) when using established clinical cut-off scores. High rates of curved angle, omission, distorted relation between elements, spatial disorganization and three-dimensional design errors were found across the four-pointed star, intersecting pentagons, and the Necker cube in both healthy participants and those with ad. Exploratory receiver operating characteristic curve analysis revealed that, with perhaps the exception of the Greek cross, meaningful sensitivity and specificity could not be reached for the four-pointed star, intersecting pentagons, and Necker cube. CONCLUSION: Cognitively healthy immigrants with low education appear to be at a disadvantage when completing visuoconstructional drawing tests, as their performance may be misinterpreted as indicating cognitive impairment. Future research is needed to identify alternative approaches to assess visuoconstructional ability in culturally and linguistically diverse older cohorts with limited education.

Visuoconstructional impairment in DM1: exploring underlying cognitive processes through the Rey complex figure.

INTRODUCTION: Among the cognitive difficulties shown by myotonic dystrophy type 1 (DM1) patients, visuoconstructional impairment - specifically measured with the Rey-Osterrieth Complex Figure Test (RCFT) - is particularly notable. This study aimed to analyze the performance of DM1 patients and healthy controls (HC) in the RCFT, using different correction systems in order to explore the cognitive processes underlying the poor performance and its associations with other signs and symptoms. METHODS: Data from 66 DM1 patients and 68 HC were included in this study. All participants had a comprehensive neuropsychological assessment, including the RCFT, which was scored using both the traditional Osterrieth and the Boston Qualitative Scoring System (BQSS) procedures. ANCOVA and Spearman's correlation analyses were conducted. RESULTS: DM1 Patients obtained significantly poorer scores than HC on the RCFT using both correction systems. Regarding BQSS, patients performed worse than HC in both main indexes (Copy Presence Accuracy-CPA and Organization-ORG), and specifically on scores of Configural accuracy, Planning, and Perseveration. Both main indexes - but especially CPA - showed significant and strong correlations with several clinical and cognitive variables. CONCLUSIONS: Both visuoconstruction and organizational impairments underlie the poor RCFT performance in DM1. Moreover, visuoconstruction ability appears to be sensitive to the clinical hallmarks of DM1 patients. The RCFT is proposed as a gold standard in DM1 assessment and the merits of using alternative scoring systems are discussed.

Visuospatial processing skills following unilateral arterial ischemic stroke in childhood.

Due to the rare occurrence of childhood stroke, its impact on later cognitive functioning remains unclear. While it is often assumed that children recover better than adults, recent studies suggest that childhood stroke can negatively affect a wide range of cognitive domains, such as attention, language, and processing speed, among others. We examined the effect of unilateral stroke on children's visuoconstructive ability and visual memory. Seventeen children with left- or right-sided arterial ischemic stroke were tested using subtests of the Hamburg-Wechsler Intelligenztest für Kinder and the Rey-Osterrieth Complex Figure (ROCF). The ROCF was evaluated both quantitatively and qualitatively with the help of two separate scoring methods. We found that lesion laterality and age at stroke impacted childhood stroke patients' ability to recall certain elements of the figure. Regarding lesion laterality, left-sided stroke patients had more difficulties recalling internal details than right-sided stroke patients. In terms of age, patients with stroke onset before the age of 5 years remembered fewer structural elements than patients with stroke onset after the age of 5 years did. Moreover, the qualitative scoring method better differentiated between individuals and between groups than the more commonly used quantitative method. The results of this study not only highlight the importance of a qualitative assessment of the ROCF but could also aid clinicians in testing stroke patients more accurately and tailoring subsequent therapy to the patient's individual needs.

Drawing a line?-Visuo-constructive function as discriminator between healthy individuals, subjective cognitive decline, mild cognitive impairment and Alzheimer's disease and predictor of disease progress compared to a multimodal approach.

PURPOSE: One cognitive domain impaired in Alzheimer's disease (AD) is visuo-construction. The Vienna Visuo-constructional Test 3.0 Screening (VVT 3.0 Screening) measures this cognitive domain. This study examines how it works in the differentiation of AD from healthy controls (HC) and the prodromal stages subjective cognitive decline (SCD) and mild cognitive impairment (MCI) and also how it performs in prediction of progress compared to the Mini Mental State Examination (MMSE) and the Sunderland Clock Drawing Test (CDT). METHODS: Data from 622 patients (33 HC, 68 SCD, 301 MCI, 220 AD) who completed all three tests were obtained. Furthermore, 117 patients were examined in a follow-up. Data were analyzed in a retrospective analysis comparing the validity of tests in diagnosis and prediction using receiver operator characteristic (ROC) curves and multinominal logistic regression. RESULTS: The VVT 3.0 Screening shows some ability to discriminate between AD and all other participants (sensitivity: 62.1%, specificity: 83.1%), while of the three examined tests none was able to predict membership to all experimental groups or to predict disease-progress adequately. As the VVT 3.0 Screening is short, easy to apply and largely language independent, it can be considered an alternative to the MMSE in certain situations. CONCLUSIONS: The VVT 3.0 Screening is useful to discriminate between AD and all other participants and can be an alternative to the MMSE in certain situations.

Preserved visuoconstruction in patients with Alzheimer's pathology and anti-neural autoantibodies: A case control study.

Background: Alzheimer's disease (AD) is seldom reported to be associated with neural autoantibodies apart from those involved in axonal neurodegeneration and amyloidopathy in prior studies. Nevertheless, this is an under-investigated aspect of AD. As we do not know whether additional screening for autoantibodies in AD patients has additional diagnostic and therapeutic value, this study aims to shed light on whether visuoconstructive or figural memory capacities might distinguish these patient populations. Methods: In this pilot case series, we investigated eight patients suffering from cognitive impairment associated with cerebrospinal fluid (CSF)-based Alzheimer pathology (AP) and with verified anti-neural autoantibodies (AP Aab+) compared to eight AD patients presenting no autoantibodies (Aab-) (AD Aab-). Patients files were reviewed retrospectively regarding their neuropsychological profile assessed via the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery and psychopathology measured by the AMDP (Manual for the Assessment and Documentation of Psychopathology in Psychiatry) system. We also relied on diagnostic parameters as in the CSF and magnetic resonance images. Results: All patients shared the same pattern of dysfunctional word-list learning and word-list recall resembling a hippocampus-dependent memory dysfunction. Furthermore, both patient groups revealed a CSF profile concurring with Alzheimer's disease. However, visuoconstructive capacity, but not figure recall was preserved in AP Aab+ patients, but not in AD Ab-patients with the shared hippocampus-based memory dysfunction. We observed no relevant differences between the AP Aab+ and AD Aab- groups in CSF cell-counts or intrathecal IgG synthesis. The relative frequency of hippocampal and focal atrophy did not differ either between AP Aab+ and AD Aab- groups. Discussion: Our pilot findings are encouraging us to conduct large-scale studies to replicate our discovery of preserved visuoconstruction in AP Aab+ patients with hippocampus-based memory dysfunction. The role of anti-neural autoantibodies is still not fully understood. The detection of these autoantibodies might imply another disease pathology that could be either neuroprotective or be affecting other brain regions, i.e., less pronounced disease activity in the right temporo-parietal regions mainly involved in visuoconstruction.

A Multimodal Neuroimaging and Neuropsychological Study of Visual Hallucinations in Alzheimer's Disease.

BACKGROUND: Hallucinations in Alzheimer's disease (AD) have been linked to more severe cognitive and functional decline. However, research on visual hallucinations (VH), the most common type of hallucinations in AD, is limited. OBJECTIVE: To investigate the cognitive and cerebral macrostructural and metabolic features associated with VH in AD. METHODS: Twenty-four AD patients with VH, 24 with no VH (NVH), and 24 cognitively normal (CN) matched controls were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Differences in regional gray matter (GM) volumes and cognitive performance were investigated with whole brain voxel-based morphometry analyses of MRI structural brain scans, and analyses of neuropsychological tests. Glucose metabolic changes were explored in a sub-sample of patients who had FDG-PET scans available. RESULTS: More severe visuoconstructive and attentional deficits were found in AD VH compared with NVH. GM atrophy and hypometabolism were detected in occipital and temporal areas in VH patients in comparison with CN. On the other hand, NVH patients had atrophy and hypometabolism mainly in temporal areas. No differences in GM volume and glucose metabolism were found in the direct comparison between AD VH and NVH. CONCLUSION: In addition to the pattern of brain abnormalities typical of AD, occipital alterations were observed in patients with VH compared with CN. More severe visuoconstructive and attentional deficits were found in AD VH when directly compared with NVH, and might contribute to the emergence of VH in AD.

Functional Specificity of TPS Brain Stimulation Effects in Patients with Alzheimer's Disease: A Follow-up fMRI Analysis.

INTRODUCTION: Transcranial pulse stimulation (TPS) has been recently introduced as a novel clinical brain stimulation technique based on highly focused ultrasound pressure pulses. In a first pilot study on clinical effects of navigated and focused ultrasound neuromodulation, a dichotomy of functional effects was found: patients with Alzheimer's disease improved cognition and language but deteriorated with visuo-constructive functions. METHODS: We analyzed changes in functional connectivity measured with functional magnetic resonance imaging (fMRI) using graph analysis of a visuo-constructive network in 18 patients with Alzheimer's disease. We calculated the network's global efficiency and tested for correlation with visuo-constructive test scores to explain this dichotomy. RESULTS: Important visuo-constructive network nodes were not stimulated in the pilot setting and correspondingly global efficiency of a visuo-constructive network was decreased after TPS therapy, compatible with a natural progress of the disease. A correlation between visuo-constructive scores and changes in global efficiency was found. CONCLUSION: Results argue for a high functional specificity of ultrasound-based neuromodulation with TPS.

Over the last decade, there has been growing interest in ultrasound-based non-invasive brain stimulation techniques in neuroscience and as a potential therapy for disorders of the brain. Transcranial pulse stimulation (TPS) has been introduced as an innovative neuromodulation technique, applying ultrashort pressure pulses through the skull into neural tissue with 3D navigation in real time. In the first clinical pilot study, patients suffering from Alzheimer's disease showed an increase in memory and language functions for up to 3 months after TPS therapy. However, visuo-constructive capacities (e.g., copying a geometrical figure) worsened. Notably, brain areas relevant for such processes had been left out during stimulation. This begged the question whether the brain areas that were targeted for brain stimulation as well as functional changes could explain this diverse response pattern. We therefore analyzed functional magnetic resonance data from patients. Specifically, we compared graph theoretical functional connectivity measures in a visuo-constructive network before and after TPS therapy. We found a decrease in connectivity in a central network node, which also correlated with visuo-constructive test scores. This deterioration is likely associated with normal disease progression. Together with the already reported improvement in global cognitive functions, these results argue for a functional specific effect of TPS.

Age-related cognitive decline in myotonic dystrophy type 1: An 11-year longitudinal follow-up study.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is an inherited multi-systemic disease involving the central nervous system (CNS) and is consequently characterized by a range of cognitive impairments. However, whether this cognitive profile progresses over time is still a matter of debate. The aim of this study was to longitudinally assess a DM1 sample, in order to compare, for the first time, this progression with that of a control group. Clinical and socio-demographic predictive factors potentially implicated in this possible decline are analysed. METHOD: Seventy-five DM1 patients with childhood, juvenile, adult, and late-onset, and 54 control participants were re-assessed in an 11-year follow-up with a comprehensive neuropsychological battery. The analyses employed were mixed ANOVA for repeated measures to test intergroup comparisons over time and multiple linear regression for predictive variable analysis. RESULTS: Myotonic dystrophy type 1 patients significantly worsened in visuospatial/visuoconstructive abilities and visual memory compared with controls. Multiple linear regression revealed that progression of cognitive impairment measured by copy of the Rey-Osterrieth complex figure was predicted by muscular impairment, whilst on the block design test age predicted the change with a cut-off at 31 years of age. DISCUSSION: A domain-specific progressive cognitive decline was found in DM1, with visuospatial/visuoconstructive abilities showing the greatest vulnerability to the passage of time. In addition to important clinical implications, these results suggest the need for the scientific community to delve deeper into the potential mechanisms underlying early cognitive decline in this population.

Exploring the behavioral and cognitive phenotype of KBG syndrome.

KBG syndrome is a neurodevelopmental disorder, caused by dominant mutations in ANKRD11, that is characterized by developmental delay/intellectual disability, mild craniofacial dysmorphisms, and short stature. Behavior and cognition have hardly been studied, but anecdotal evidence suggests higher frequencies of ADHD-symptoms and social-emotional impairments. In this study, the behavioral and cognitive profile of KBG syndrome will be investigated in order to examine if and how cognitive deficits contribute to behavioral difficulties. A total of 18 patients with KBG syndrome and a control group consisting of 17 patients with other genetic disorders with comparable intelligence levels, completed neuropsychological assessment. Age-appropriate tasks were selected, covering overall intelligence, attention, memory, executive functioning, social cognition and visuoconstruction. Results were compared using Cohen's d effect sizes. As to behavior, fewer difficulties in social functioning and slightly more attentional problems, hyperactivity, oppositional defiant behavior and conduct problems were found in the KBG syndrome group. Regarding cognitive functioning, inspection of the observed differences shows that patients with KBG syndrome showed lower scores on sustained attention, cognitive flexibility, and visuoconstruction. In contrast, the KBG syndrome group demonstrated higher scores on visual memory, social cognition and emotion recognition. The cognitive profile of KBG syndrome in this sample indicates problems in attention and executive functioning that may underlie the behavior profile which primarily comprises impulsive behavior. Contrary to expectations based on previous (case) reports, no deficits were found in social cognitive functioning. These findings are important for counseling purposes, for tailored education planning, and for the development of personalized intervention.

Real-world navigation in amnestic mild cognitive impairment: The relation to visuospatial memory and volume of hippocampal subregions.

Spatial disorientation is a frequent symptom in Alzheimer's disease and in mild cognitive impairment (MCI). In the clinical routine, spatial orientation is less often tested with real-world navigation but rather with 2D visuoconstructive tasks. However, reports about the association between the two types of tasks are sparse. Additionally, spatial disorientation has been linked to volume of the right hippocampus but it remains unclear whether right hippocampal subregions have differential involvement in real-world navigation. Yet, this would help uncover different functional roles of the subregions, which would have important implications for understanding the neuronal underpinnings of navigation skills. We compared patients with amnestic MCI (aMCI; n = 25) and healthy elderly controls (HC; n = 25) in a real-world navigation task that engaged different spatial processes. The association between real-world navigation and different visuoconstructive tasks was tested (i.e., figures from the Consortium to Establish a Registry for Alzheimer's Disease; CERAD, the Rey-Osterrieth Complex Figure task; and clock drawing). Furthermore, the relation between spatial navigation and volume of right hippocampal subregions was examined. Linear regression and relative weight analysis were applied for statistical analyses. Patients with aMCI were significantly less able to correctly navigate through a route compared to HC but had comparable map drawing and landmark recognition skills. The association between visuoconstructive tasks and real-world navigation was only significant when using the visuospatial memory component of the Rey figure. In aMCI, more volume of the right hippocampal tail was significantly associated with better navigation skills, while volume of the right CA2/3 region was a significant predictor in HC. Standard visuoconstructive tasks (e.g., the CERAD figures or clock drawing) are not sufficient to detect real-world spatial disabilities in aMCI. Consequently, more complex visuoconstructive tasks (i.e., the Rey figure) should be routinely included in the assessment of cognitive functions in the context of AD. Moreover, in those elderly individuals with impaired complex visuospatial memory, route finding behaviour should be evaluated in detail. Regarding the contribution of hippocampal subregions to spatial navigation, the right hippocampal tail seems to be particularly important for patients with aMCI, while the CA2/3 region appears to be more relevant in HC.

Visuoconstructional Impairment in Subtypes of Mild Cognitive Impairment.

Clock Drawing Test performance was examined alongside other neuropsychological tests in mild cognitive impairment (MCI). We tested the hypothesis that clock-drawing errors are related to executive impairment. The current research examined 86 patients with MCI for whom, in prior research, cluster analysis was used to sort patients into dysexecutive (dMCI, n = 22), amnestic (aMCI, n = 13), and multidomain (mMCI, n = 51) subtypes. First, principal components analysis (PCA) and linear regression examined relations between clock-drawing errors and neuropsychological test performance independent of MCI subtype. Second, between-group differences were assessed with analysis of variance (ANOVA) where MCI subgroups were compared to normal controls (NC). PCA yielded a 3-group solution. Contrary to expectations, clock-drawing errors loaded with lower performance on naming/lexical retrieval, rather than with executive tests. Regression analyses found increasing clock-drawing errors to command were associated with worse performance only on naming/lexical retrieval tests. ANOVAs revealed no differences in clock-drawing errors between dMCI versus mMCI or aMCI versus NCs. Both the dMCI and mMCI groups generated more clock-drawing errors than the aMCI and NC groups in the command condition. In MCI, language-related skills contribute to clock-drawing impairment.

The Genesis of Graphic Perseverations in Alzheimer's Disease and Vascular Dementia.

OBJECTIVE: Perseveration is the involuntary production of iterative responses. This study explored graphic perseverative errors in Alzheimer's disease and vascular dementia, to comprehend the neuropsychological correlates of this behavior. METHOD: We performed a retrospective analysis of graphic productions in 114 individuals with clinical diagnosis of Alzheimer's disease and in 63 individuals with clinical diagnosis of vascular dementia, who completed frontal-executive, visuo-spatial, visuo-constructional, and verbal memory tests. For assessing perseverative behavior, we considered recurrent perseverations (inappropriate re-drawing of a figure drawn in a previous trial) and continuous perseverations (inappropriate replication of the same figure or of its element within one trial) produced in a standard copying task. RESULTS: Two or more graphic perseverative errors occurred in 66/114 individuals with Alzheimer's disease (57.9%) and in 31/63 individuals with vascular dementia (49.2%). Participants with moderate-to-severe dementia produced a significantly higher number of perseverations than individuals with mild dementia. Logistic regression revealed a significant relationship of graphic perseverations with frontal and visuo-constructive impairments, in both Alzheimer's disease and vascular dementia. CONCLUSIONS: Graphic perseverations are frequent in both Alzheimer's disease and vascular dementia. Frontal-executive defects can hamper inhibition of iterative graphic productions. Identification of graphic perseverations can be useful for detection and monitoring of frontal-executive impairments throughout the disease course in individuals with dementia.