Prognostic value of cognitive impairment, assessed by the Clock Drawing Test, in emergency department patients presenting with non-specific complaints.

BACKGROUND: Cognitive impairment (CI) is common among older patients presenting to the emergency department (ED). The failure to recognize CI at ED presentation constitutes a high risk of additional morbidity, mortality, and functional decline. The Clock Drawing Test (CDT) is a well-established cognitive screening test. AIM: In patients presenting to the ED with non-specific complaints (NSCs), we aimed to investigate the usability of the CDT and its prognostic value regarding length of hospital stay (LOS) and mortality. METHOD: Secondary analysis of the Basel Non-specific Complaints (BANC) trial, a prospective delayed type cross-sectional study with a 30-day follow-up. In three EDs, patients presenting with NSCs were enrolled. The CDT was administered at enrollment. RESULTS: In the 1,278 patients enrolled, median age was 81 [74, 87] years and 782 were female (61.19%). A valid CDT was obtained in 737 (57.7%) patients. In patients without a valid CDT median LOS was higher (29 [9, 49] days vs. 22 [9, 45] days), and 30-day mortality was significantly higher than in patients with a valid CDT (n = 45 (8.32%) vs. n = 39 (5.29%)). Of all valid CDTs, 154 clocks (20.9%) were classified as normal, 55 (7.5%) as mildly deficient, 297 (40.3%) as moderately deficient, and 231 (31.3%) as severely deficient. Mortality and LOS increased along with the CDT deficits (p = 0.012 for 30-day mortality; p < 0.001 for LOS). CONCLUSION: The early identification of patients with CI may lead to improved patient management and resource allocation. The CDT could be used as a risk stratification tool for older ED patients presenting with NSCs, as it is a predictor for 30-day mortality and LOS.

A Network Analysis of Digital Clock Drawing for Command and Copy Conditions.

Graphomotor and time-based variables from the digital Clock Drawing Test (dCDT) characterize cognitive functions. However, no prior publications have quantified the strength of the associations between digital clock variables as they are produced. We hypothesized that analysis of the production of clock features and their interrelationships, as suggested, will differ between the command and copy test conditions. Older adults aged 65+ completed a digital clock drawing to command and copy conditions. Using a Bayesian hill-climbing algorithm and bootstrapping (10,000 samples), we derived directed acyclic graphs (DAGs) to examine network structure for command and copy dCDT variables. Although the command condition showed moderate associations between variables (µ|ßz|= 0.34) relative to the copy condition (µ|ßz| = 0.25), the copy condition network had more connections (18/18 versus 15/18 command). Network connectivity across command and copy was most influenced by five of the 18 variables. The direction of dependencies followed the order of instructions better in the command condition network. Digitally acquired clock variables relate to one another but differ in network structure when derived from command or copy conditions. Continued analyses of clock drawing production should improve understanding of quintessential normal features to aid in early neurodegenerative disease detection.

Digital Clock Drawing as an Alzheimer's Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection. OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker. DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures. SETTING: We used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date. PARTICIPANTS: The sample consisted of 2,398 older adults ages 60-94 with DCTclockTM data (mean age of 72.3, 55% female and 92% White). MEASUREMENTS: PRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD). RESULTS: Results showed that DCTclockTM performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclockTM Total Score as well as lower composite scores for Information Processing Speed (both command and copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women. CONCLUSIONS: Our results indicate that higher AD genetic risk is associated with poorer DCTclockTM performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS.

Arterial Hypertension, Structural Damage of the Brain and Cognitive Test / Hipertensión arterial, daño estructural del cerebro y test cognitivos.

Introduction: The arterial hypertension cause brain vascular damage (white matter lesion) and the burden and progression determine their cognitive consequences. Therefore, arterial hypertension is considered the main modifiable vascular risk factor for cognitive impairment and dementia. Therefore, the aim of the current study was to evaluate the results of cognitive tests in a sample of hypertensive patients and to establish possible associations with structural brain lesions (atrophy, white matter lesions) identified by magnetic resonance imaging Methods: Were included 70 hypertensive patients from Heart-Brain study in Argentina with magnetic resonance imaging and cognitive test. Fazekas scale and the Global Cortical Atrophy were used to quantify the white matter lesions and the brain atrophy, respectively. The Mini-Mental Status Examination, Clock Drawing test and Mini-Boston Naming test were used to evaluate the cognitive status. Results: average age 69.7 ± 10.6 years, 55.7% female). Based on the linear regression analysis, Fazekas scale and cognitive tests were inversely associated. For each grade of increase in Fazekas scale, the clock drawing test (Coef -0.56, CI 95% -1.01 -0.10, p=0.01) and the Mini-mental Status Examination (Coef -0.7, CI 95% -1.27 -0.13, p=0.01) scores decreased. The subcortical atrophy was significantly associated with the clock drawing test (OR 3.29, CI 95% 1.25-8.63; p=0.016). Conclusion: The cognitive tests, particularly the clock drawing test could be used (in the clinical routine practice) as "subrrogate" of the brain structural hypertension-mediated damage.

Introducción: La hipertensión arterial causa daño vascular cerebral (lesiones de sustancia blanca) y su carga y progresión determinan las consecuencias cognitivas. Así, la hipertensión es considerada el principal factor de riesgo vascular modificable para desarrollar deterioro cognitivo y demencia. Por lo tanto el objetivo de la presente investigación fue evaluar el resultado de los test cognitivos en una muestra de pacientes hipertensos y establecer las posibles asociaciones con las lesiones estructurales del cerebro (atrofia, lesiones de sustancia blanca) identificadas mediante resonancia magnética. Métodos: Se incluyeron 70 pacientes hipertensos pertenecientes al estudio Corazón-Cerebro en Argentina a los que se les realizó resonancia magnética y evaluación cognitiva. Se utilizaron las escalas de Fazekas y la Global Cortico Atrophy para evaluar las lesiones de sustancia blanca y la atrofia cerebral, respectivamente y el Mini-mental test, el test del reloj y el test de denominación Mini-Boston para conocer el estatus cognitivo. Resultados: Edad promedio 69.7 ± 10.6 años, 55.7% mujeres. Basados en el análisis de regresión lineal, la escala de Fazekas se asoció en forma inversa con los test cognitivos. Por cada punto de aumento en la escala de Fazekas el puntaje del test del reloj descendió -0.56 (IC 95% -1.01 -0.10, p=0.01) y el Mini-mental test -0.7 (IC95% -1.27 -0.13, p=0.01). La atrofia subcortical se asoció en forma inversa solo con el test del reloj (OR 3.29, IC 95% 1.25-8.63; p=0.016). Conclusión: Los test cognitivos, en especial el test del reloj, podrían ser utilizados, en la práctica clínica asistencial, como un subrogado del daño estructural del cerebro mediado por la hipertensión arterial.

Diagnostic accuracy of the Clock Drawing Test in screening for early post-stroke neurocognitive disorder: the Nor-COAST study.

BACKGROUND: Post-stroke neurocognitive disorder, though common, is often overlooked by clinicians. Moreover, although the Montreal Cognitive Assessment (MoCA) has proven to be a valid screening test for neurocognitive disorder, even more time saving tests would be preferred. In our study, we aimed to determine the diagnostic accuracy of the Clock Drawing Test (CDT) for post-stroke neurocognitive disorder and the association between the CDT and MoCA. METHODS: This study is part of the Norwegian Cognitive Impairment After Stroke study, a multicentre prospective cohort study following patients admitted with acute stroke. At the three-month follow-up, patients were classified with normal cognition, mild neurocognitive disorder, or major neurocognitive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Any neurocognitive disorder compromised both mild- and major neurocognitive disorder. The CDT at the three-month assessment was given scores ranging from 0 to 5. Patients able to complete the CDT and whose cognitive status could be classified were included in analyses. The CDT diagnostic accuracy for post-stroke neurocognitive disorder was identified using receiver operating characteristic curves, sensitivity, specificity, positive predictive value, and negative predictive value. The association between the MoCA and CDT was analysed with Spearman's rho. RESULTS: Of 554 participants, 238 (43.0%) were women. Mean (SD) age was 71.5 (11.8) years, while mean (SD) National Institutes of Health Stroke Scale score was 2.6 (3.7). The area under the receiver operating characteristic curve of the CDT for major neurocognitive disorder and any neurocognitive disorder was 0.73 (95% CI, 0.68-0.79) and 0.68 (95% CI, 0.63-0.72), respectively. A CDT cutoff of < 5 yielded 68% sensitivity and 60% specificity for any neurocognitive disorder and 78% sensitivity and 53% specificity for major neurocognitive disorder. Spearman's correlation coefficient between scores on the MoCA and CDT was 0.50 (95% CI, 0.44-0.57, p < .001). CONCLUSIONS: The CDT is not accurate enough to diagnose post-stroke neurocognitive disorder but shows acceptable accuracy in identifying major neurocognitive disorder. Performance on the CDT was associated with performance on MoCA; however, the CDT is inferior to MoCA in identifying post-stroke neurocognitive disorder. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02650531). Retrospectively registered January 8, 2016.

Digital Clock and Recall is superior to the Mini-Mental State Examination for the detection of mild cognitive impairment and mild dementia.

BACKGROUND: Disease-modifying treatments for Alzheimer's disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as the Digital Clock and Recall (DCR™), have the potential to address this need. Here, we examine the advantages of DCR over the Mini-Mental State Examination (MMSE) in detecting mild cognitive impairment (MCI) and mild dementia. METHODS: We studied 706 participants from the multisite Bio-Hermes study (age mean ± SD = 71.5 ± 6.7; 58.9% female; years of education mean ± SD = 15.4 ± 2.7; primary language English), classified as cognitively unimpaired (CU; n = 360), mild cognitive impairment (MCI; n = 234), or probable mild Alzheimer's dementia (pAD; n = 111) based on a review of medical history with selected cognitive and imaging tests. We evaluated cognitive classifications (MCI and early dementia) based on the DCR and the MMSE against cohorts based on the results of the Rey Auditory Verbal Learning Test (RAVLT), the Trail Making Test-Part B (TMT-B), and the Functional Activities Questionnaire (FAQ). We also compared the influence of demographic variables such as race (White vs. Non-White), ethnicity (Hispanic vs. Non-Hispanic), and level of education (≥ 15 years vs. < 15 years) on the DCR and MMSE scores. RESULTS: The DCR was superior on average to the MMSE in classifying mild cognitive impairment and early dementia, AUC = 0.70 for the DCR vs. 0.63 for the MMSE. DCR administration was also significantly faster (completed in less than 3 min regardless of cognitive status and age). Among 104 individuals who were labeled as "cognitively unimpaired" by the MMSE (score ≥ 28) but actually had verbal memory impairment as confirmed by the RAVLT, the DCR identified 84 (80.7%) as impaired. Moreover, the DCR score was significantly less biased by ethnicity than the MMSE, with no significant difference in the DCR score between Hispanic and non-Hispanic individuals. CONCLUSIONS: DCR outperforms the MMSE in detecting and classifying cognitive impairment-in a fraction of the time-while being not influenced by a patient's ethnicity. The results support the utility of DCR as a sensitive and efficient cognitive assessment in primary care settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04733989.

About time: neurocognitive correlates of stimulus-bound and other time setting errors in the Clock Drawing Test.

OBJECTIVE: Previous findings suggest that time setting errors (TSEs) in the Clock Drawing Test (CDT) may be related mainly to impairments in semantic and executive function. Recent attempts to dissociate the classic stimulus-bound error (setting the time to "10 to 11" instead of "10 past 11") from other TSEs, did not support hypotheses regarding this error being primarily executive in nature or different from other time setting errors in terms of neurocognitive correlates. This study aimed to further investigate the cognitive correlates of stimulus-bound errors and other TSEs, in order to trace possible underlying cognitive deficits. METHODS: We examined cognitive test performance of participants with preliminary diagnoses associated with mild cognitive impairment. Among 490 participants, we identified clocks with stimulus-bound errors (n = 78), other TSEs (n = 41), other errors not related to time settings (n = 176), or errorless clocks (n = 195). RESULTS: No differences were found on any dependent measure between the stimulus-bound and the other TSErs groups. Group comparisons suggested TSEs in general, to be associated with lower performance on various cognitive measures, especially on semantic and working memory measures. Regression analysis further highlighted semantic and verbal working memory difficulties as being the most prominent deficits associated with these errors. CONCLUSION: TSEs in the CDT may indicate underlying deficits in semantic function and working memory. In addition, results support previous findings related to the diagnostic value of TSEs in detecting cognitive impairment.

Clock-Drawing Test and Cube-Copying Test to Quickly Screen Dementia: In Combination with the Mini-Mental State Examination Scores.

Objective Due to the increasing elderly population and number of dementia patients, the current number of psychiatrists and neurologists remains insufficient to treat dementia in Japan. Therefore, a simple method for accurately performing a dementia diagnosis, including that of primary care physicians, is sought in clinical practice. Methods A retrospective study was conducted on patients who made their first visit due to amnesia between October 2020 and October 2022. The sensitivities and specificities of four spatial recognition and planning ability evaluation methods (fox finger imitation test, pentagon-copying test (PCT), cube-copying test (CCT), and clock-drawing test (CDT) ) were calculated. The difference between the Mini-Mental State Examination (MMSE) scores, as an evaluation of memory and language impairment, and CDT scores were assessed using the Mann-Whitney U test. Patients Fifty-one patients with dementia and 6 patients without dementia were examined in this study. Results The sensitivity and specificity were 31.4% and 100% for the fox finger imitation tests, 29.4% and 100% for PCT, 62% and 83.3% for CCT, and 72.5% and 100% for CDT, respectively. The sensitivity increased to 78.4% when the CCT and CDT results were combined. Spearman's rank correlation coefficient between the MMSE and CDT scores of the 51 patients with dementia showed a significantly positive correlation (r = 0.62, p <0.001). Comparing Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), the difference between the MMSE and CDT scores was significantly greater in patients with DLB. Conclusion To quickly screen for dementia, a combination of CCT and CDT is recommended for the highest sensitivity (78.4%). In addition, the difference between the CDT and MMSE scores is considered to be useful for differentiating DLB from AD.

The Clock-Drawing Test as a Useful Screening Assessment of Preoperative Cognitive Impairment with Readmission After Transcatheter Aortic Valve Implantation.

Background: Transcatheter aortic valve implantation (TAVI) has recently become more common as a treatment for severe, symptomatic aortic stenosis (AS). Cognitive impairment (CI) is strongly associated with the prognosis of TAVI patients. However, some cognitive assessments currently in use are difficult to perform routinely in the clinical setting. To easier CI evaluation, we investigated whether CI using the clock-drawing test (CDT), one part of the Mini-Cog, affects the postoperative prognosis of TAVI patients with AS. Methods: The present study enrolled 52 patients (median age, 85 years; 28.8% male) who underwent TAVI and were discharged between 2019 and 2021. The outcome was readmission for all causes within one year of discharge and patients were grouped according to whether they were readmitted or not. Cognitive function was assessed using the Mini-Cog which combines verbal playback and CDT. Results: Of the 52, 11 patients (21.2%) comprised readmission group, including 4 (36.4%) each for fracture and infection, and 1 (9.1%) each for heart failure, subdural hematoma, and pneumothorax. Median Mini-Cog score was lower in the readmission group than in the non-readmission group (4 vs. 5; P < 0.05). The frequency of Mini-Cog score < 3 (indicative of CI) and CDT failure were significantly higher in the readmission group than in the non-readmission group, respectively (46% vs. 7%, P < 0.01) (46% vs. 12%, P < 0.05). Both of Mini-Cog score < 3 and CDT failure were independently associated with readmission. The areas under the curve showed CDT was an indicator of readmission with similar accuracy to the Mini-Cog score < 3. Kaplan-Meier curves showed significant differences in readmission after 1 year between the 2 Mini-Cog groups with scores of < 3 or ≥ 3 points and CDT failure and success. Conclusion: The CDT may be a very easy and simple screening assessment of preoperative CI with readmission within one year after TAVI.

Detection of Alzheimer's Disease Using Logistic Regression and Clock Drawing Errors.

Alzheimer's disease is an incurable disorder that accounts for up to 70% of all dementia cases. While the prevalence of Alzheimer's disease and other types of dementia has increased by more than 160% in the last 30 years, the rates of undetected cases remain critically high. The present work aims to address the underdetection of Alzheimer's disease by proposing four logistic regression models that can be used as a foundation for community-based screening tools that do not require the participation of medical professionals. Our models make use of individual clock drawing errors as well as complementary patient data that is highly available and easily collectible. All models were controlled for age, education, and gender. The discriminative ability of the models was evaluated by area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow test, and calibration plots were used to assess calibration. Finally, decision curve analysis was used to quantify clinical utility. We found that among 10 possible CDT errors, only 3 were informative for the detection of Alzheimer's disease. Our base regression model, containing only control variables and clock drawing errors, produced an AUC of 0.825. The other three models were built as extensions of the base model with the step-wise addition of three groups of complementary data, namely cognitive features (semantic fluency score), genetic predisposition (family history of dementia), and cardio-vascular features (BMI, blood pressure). The addition of verbal fluency scores significantly improved the AUC compared to the base model (0.91 AUC). However, further additions did not make a notable difference in discriminatory power. All models showed good calibration. In terms of clinical utility, the derived models scored similarly and greatly outperformed the base model. Our results suggest that the combination of clock symmetry and clock time errors plus verbal fluency scores may be a suitable candidate for developing accessible screening tools for Alzheimer's disease. However, future work should validate our findings in larger and more diverse datasets.

Poor preoperative performance at Clock Drawing Test is associated with postoperative decline in olfaction in older patients: an observational pilot study.

BACKGROUND: Decline in olfaction may occur after general anesthesia, but the exact incidence and underlying physiopathology remain scarcely investigated. Olfactory dysfunction arises with aging and is known to be linked to cognitive impairment. In this pilot study, we evaluated the incidence of immediate postoperative decline in olfaction and its association with a preoperative cognitive test, performance at Clock Drawing Test (CDT), in a group of older patients. METHODS: This pilot study is a sub-analysis of a prospective observational study. Patients ≥ 65 years old and scheduled for elective non-cardiac surgery under sevoflurane-based anesthesia were enrolled. CDT was part of the preoperative evaluation. We assessed olfaction on the day before and the day after surgery (between 16 and 26 h postoperatively) using the Sniffin' Sticks 12-item identification test, which consists of pen-like devices displaying 12 different odors. Postoperative decline in olfaction was defined as a decrease of at least 1 standard deviation in the olfactory score. RESULTS: We included a total of 93 patients, among whom 19 (20.4%) presented a postoperative decline in olfaction. The incidence of postoperative decline in olfaction was higher in the "CDT low-score" (score ≤ 5/8) group (11/34, 32.4%) than in the "CDT high-score" (score ≥ 6/8) group (8/58, 13.6%) (P = 0.030). Despite adjusting for confounding variables, CDT score remained independently associated with immediate postoperative decline in olfactory identification function (OR 0.67, 95% CI 0.48 to 0.94, P = 0.022). CONCLUSIONS: Postoperative decline in olfaction occurred in 20.4% of older patients and was associated with poor preoperative performance at CDT. TRIAL REGISTRATION: This study was retrospectively registered on https://clinicaltrials.gov/ under the NCT04700891 number (principal investigator: Victoria Van Regemorter), in December 2020.

Cognitive Performance in Asymptomatic Elderly People with Hepatitis C: The Role of Education.

BACKGROUND: Neurotropism of the hepatitis C virus (HCV) can be the source of subtle neuropsychological symptoms in non-cirrhotic patients. Age is a risk factor for cognitive impairment (CI). Thus, asymptomatic elderly people who carry HCV might be at a greater risk of CI. Education can influence test performance. OBJECTIVES: (1) To verify whether elderly people with HCV performed poorer than controls on cognitive tests. (2) To analyze how education affects performance. (3) To verify whether the extent of the effect of education on performance depends on the group (HCV vs. controls) and the type of cognitive test. METHODS: Asymptomatic HCV carriers older than 60 years (n = 41) were matched with 41 corresponding controls. All participants performed the following tests: Mini-Cog, Mini Mental State Examination, clock drawing test (CDT), and verbal fluency. RESULTS: (1) There were no significant differences in cognitive performance between the two groups. (2) Higher education was always associated with better performance. (3) There was a significant group difference in the slopes of the regression lines between years of education and CDT performance. No differences were found for the other three tests. CONCLUSION: Considering the scores on the CDT, the rate of improvement in performance when schooling increases is higher in HCV carriers.

The clock drawing test is an important contribution to the Mini Mental State Examination in screening for cognitive impairment.

BACKGROUND: The clock drawing test (CDT) and the Mini Mental State Examination (MMSE) are frequently used screening instruments for cognitive impairment, however, the precise contribution of the CDT to the MMSE is largely unknown. METHODS: We studied patients with subjective cognitive impairment (SCI, n = 481), mild cognitive impairment (MCI, n = 628) and Alzheimer's disease (AD, n = 1099). Discrimination between patients was examined with multiple logistic regression, adjusted for age, sex, and education. Four groups were constructed based on a normal/abnormal MMSE (cut-off <24/30) versus normal/abnormal CDT (cut-off ≤2/3). Visually rated medial temporal lobe atrophy (MTA) on CT was used as parameter of neurodegeneration. RESULTS: The CDT significantly contributed to the MMSE in discriminating SCI from both MCI and AD patients. Our four group analyses showed that of those patients with a normal MMSE and incorrectly classified as SCI, an abnormal CDT could significantly identify 10.0% as MCI and 13.2% as AD. Among those with an abnormal MMSE, the percentage AD patients shifted from 53.1% to 82.1% due to an abnormal CDT. Presence of an abnormal CDT was significantly related to MTA increase, regardless of the MMSE score. CONCLUSION: The CDT is an important additional screening tool to the MMSE. An abnormal CDT with a normal MMSE is an indicator for cognitive impairment. An abnormal CDT in combination with an abnormal MMSE can be considered as an indicator of disease progression.

Outcome of visuospatial dysfunction assessment in patients with Parkinson's disease using mobile application software.

Background: Visuospatial dysfunction and cognitive impairment are common in Parkinson's disease (PD), which draw increasing attention in the current literature. But clinicians still lack rapid, effective and unified cognitive battery for visuospatial assessment. Objective: A new approach was studied to explore the feasibility of using mobile application software (APP) to evaluate visuospatial dysfunction in patients with PD and compared with traditional assessment tools. We aimed to verify the threshold score of the APP for early diagnosis. Materials and methods: A total of 41 patients with PD underwent assessments using several test modules including Digit Symbol Test (DST), Visual Organization Test (VOT), Facial Recognition Test (FRT), Vocabulary Memory Test (VMT) of this APP, as well as Clock Drawing Test (CDT), Cube Copying Test (CCT) and the Mini-Mental State Examination (MMSE) for comparison. Among the 41 PD patients, 30 individuals were found to have visuospatial dysfunction based on CDT score < 5 and CCT score of<18 while the remaining 11 patients served as control. Results: There were statistically significant differences in DST, VOT, and FRT scores (all p ≤ 0.001 for group comparisons). DST, VOT, and FRT-1 were significantly correlated with MMSE, CDT and CCT and the correlations were moderate or fairly strong. For visuospatial dysfunction diagnosis, all the areas under curves (AUC) of DST, VOT, and FRT-1 were statistically significant (p < 0.0001, p = 0.0002, and p = 0.0002, respectively). The estimates and 95% confidence intervals of AUC were 0.8303 (0.6868, 0.9739), 0.8045 (0.6423, 0.9668), and 0.7833 (0.6344, 0.9322), respectively. Their cut-off points for visuospatial dysfunction were 26, 17, and 19, respectively. After dichotomization by the cut-off points, DST had high sensitivity of 96.67% while VOT and FRT-1 had high specificity of 81.82 and 90.91%. Conclusion: This study demonstrated that visuospatial disorders was highly prevalent in PD patients, and the APP used in study could be a practical clinical screening tool for visuospatial ability assessment with high sensitivity and specificity.

Relationship between Brain-Derived Neurotrophic Factor and Cognitive Decline in Patients with Mild Cognitive Impairment and Dementia.

In the last decade, increasing evidence has emerged linking alterations in the brain-derived neurotrophic factor (BDNF) expression with the development of Alzheimer's disease (AD). Because of the important role of BDNF in cognition and its association with AD pathogenesis, the aim of this study was to evaluate the potential difference in plasma BDNF concentrations between subjects with mild cognitive impairment (MCI; N = 209) and AD patients (N = 295) and to determine the possible association between BDNF plasma levels and the degree of cognitive decline in these individuals. The results showed a significantly higher (p < 0.001) concentration of plasma BDNF in subjects with AD (1.16; 0.13-21.34) compared with individuals with MCI (0.68; 0.02-19.14). The results of the present study additionally indicated a negative correlation between cognitive functions and BDNF plasma concentrations, suggesting higher BDNF levels in subjects with more pronounced cognitive decline. The correlation analysis revealed a significant negative correlation between BDNF plasma levels and both Mini-Mental State Examination (p < 0.001) and Clock Drawing test (p < 0.001) scores. In conclusion, the results of our study point towards elevated plasma BDNF levels in AD patients compared with MCI subjects, which may be due to the body's attempt to counteract the early and middle stages of neurodegeneration.

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.

Using Explainable Artificial Intelligence in the Clock Drawing Test to Reveal the Cognitive Impairment Pattern.

The prevalence of dementia is currently increasing worldwide. This syndrome produces a deterioration in cognitive function that cannot be reverted. However, an early diagnosis can be crucial for slowing its progress. The Clock Drawing Test (CDT) is a widely used paper-and-pencil test for cognitive assessment in which an individual has to manually draw a clock on a paper. There are a lot of scoring systems for this test and most of them depend on the subjective assessment of the expert. This study proposes a computer-aided diagnosis (CAD) system based on artificial intelligence (AI) methods to analyze the CDT and obtain an automatic diagnosis of cognitive impairment (CI). This system employs a preprocessing pipeline in which the clock is detected, centered and binarized to decrease the computational burden. Then, the resulting image is fed into a Convolutional Neural Network (CNN) to identify the informative patterns within the CDT drawings that are relevant for the assessment of the patient's cognitive status. Performance is evaluated in a real context where patients with CI and controls have been classified by clinical experts in a balanced sample size of [Formula: see text] drawings. The proposed method provides an accuracy of [Formula: see text] in the binary case-control classification task, with an AUC of [Formula: see text]. These results are indeed relevant considering the use of the classic version of the CDT. The large size of the sample suggests that the method proposed has a high reliability to be used in clinical contexts and demonstrates the suitability of CAD systems in the CDT assessment process. Explainable artificial intelligence (XAI) methods are applied to identify the most relevant regions during classification. Finding these patterns is extremely helpful to understand the brain damage caused by CI. A validation method using resubstitution with upper bound correction in a machine learning approach is also discussed.

Predictive ability of the clock drawing test to detect mild cognitive impairment and dementia over time: Results from the HELIAD study.

Objective: We investigated the diagnostic accuracy of the Clock Drawing Test (CDT) in discriminating Mild Cognitive Impairment (MCI) and dementia from normal cognition. Additionally, its clinical utility in predicting the transition from normal cognition to MCI and dementia over the course of several years was explored. Method: In total, 1037 older adults (633 women) who completed the CDT in a baseline assessment were drawn from the population-based HELIAD cohort. Among these, 848 participants were identified as cognitively normal, 142 as having MCI and 47 with dementia during the baseline assessment. Of these individuals, 565 attended the follow-up assessment (mean interval: 3.21 years). ROC curve and binary logistic regression analyses were performed. Results: The CDT exhibited good diagnostic accuracy for the discrimination between dementia and normal cognition (AUC = .879, SN = .813, SP = .778, LR+ = 3.66, LR- = .240, < .001, d = 1.655) and acceptable diagnostic accuracy for the discrimination between dementia and MCI (AUC=.761, SN= .750, SP= .689, LR+ = 2.41, LR- = .362, p < .001, d = 1.003). We found limited diagnostic accuracy, however, for the discrimination between MCI and normal cognition (AUC = .686, SN = .764, SP = .502, LR+ = 1.53, LR- = .470, p < .001, d = .685). Moreover, the CDT significantly predicted the transition from normal cognition to dementia [Exp(B)= 1.257, p = .022], as well as the transition from MCI to normal cognition [Exp(B) = 1.334, p = .023] during the longitudinal investigation. Conclusions: The CDT is a neuropsychological test with acceptable diagnostic accuracy for the discrimination of dementia from MCI and normal cognition. Furthermore, it has an important predictive value for the transition from normal cognition to dementia and from MCI to normal cognition.

The Value of Clock Drawing Process Assessment in Screening for Mild Cognitive Impairment and Alzheimer's Dementia.

Many clock drawing test (CDT) scoring systems focus on drawing results and lack drawing process assessments. This study created a CDT scoring procedure with drawing process assessment and explored its diagnostic value in screening for mild cognitive impairment (MCI) and early Alzheimer's disease (AD) from normal control (NC). We used logistic regression and receiver operating characteristic (ROC) curves to determine a new, sensitive scoring system for AD and MCI patients in a derivation cohort. The new scoring method was then compared to two common scoring systems and externally validated in a second cohort. We developed a new scoring system named CDT5, which contained one process assessment item: remember setting time without asking. Compared with two published scoring systems, CDT5 had better discriminatory power in distinguishing AD patients from NCs in derivation (area under the ROC curve [area under the curve, AUC] = .890) and validation (AUC = .867) cohorts. Three scoring systems had poor diagnostic accuracy at discriminating MCI patients from controls, with CDT5 being the most sensitive (78.57%). Adding the drawing process in CDT helps accurately detect patients with early AD, but its role in identifying patients with MCI needs to be further explored.

More than a third of middle-aged adults (50-65) have understated executive dysfunction.

OBJECTIVES: Understated executive dysfunction (UED) is predictive of cognitive decline and death. We aimed to assess the prevalence of UED, assessed with the clock-drawing test (CDT) and the Frontal Assessment Battery (FAB) in middle-aged adults and to investigate associated characteristics. METHODS: Cross-sectional analysis of data on 516 community-dwellers aged 50-65, lacking cognitive complaints, who were included prospectively (2010-2017) after a multidimensional geriatric assessment at a "healthy ageing" outpatient clinic. Age- and educational-level-adjusted logistic models were used to assess factors associated with UED. RESULTS: The CDT and FAB were impaired in 27.7% and 14.7% of the participants (median age: 59.7 years). The prevalence [95% confidence interval (CI)] of UED was 36.2% [32.2-40.5%]. After adjustment for age and education, participants with UED were more likely to be obese (odds ratio [95%CI] = 1.89 [1.12-3.19], P = 0.02), and to have a metabolic syndrome (1.98 [1.06-3.72], P = 0.03). CONCLUSION: More than one third of middle-aged adults without cognitive complaints have UED, which was linked to obesity and metabolic syndrome. Cognitive screening tests targeting executive functions might be useful for early detection of UED and the initiation of multidomain interventions improving cognitive performance.