Association between executive function and the evolution of behavioral disorders in Alzheimer's disease.

OBJECTIVE: This study was aimed at evaluating the association between cognitive functioning and the occurrence of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD). METHODS/DESIGN: The population is derived from the PACO cohort, including 237 patients with prodromal or mild AD. A neuropsychological tests battery exploring verbal and visual memory, language, attention, and executive functions was performed at baseline. BPSD were assessed at 6-, 12-, and 18-month follow-up with neuropsychiatric inventory (NPI). RESULTS: Lower baseline performance on Stroop test interference score was associated with higher subsequent overall NPI scores (P = .006), subscores of anxiety/depression (P = .03), and apathy inventory (P = .01). Conversely, other executive functions, verbal or visual memory, and language performances were not associated with a higher risk of BPSD. CONCLUSION: Our results suggest that poorer inhibition performance would be associated with a higher risk of 18-month BPSD occurrence, including anxiety, depression, and apathy. A better knowledge of the predictive factors of the BPSDs would make it possible to better identify the patients at risk, to propose preventive strategies and an earlier adapted care. J Am Geriatr Soc 68:-, 2020.

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BACKGROUND: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions. METHODS: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months. DISCUSSION: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns. TRIAL REGISTRATION: NCT02052947 .

Personality, Alzheimer's disease and behavioural and cognitive symptoms of dementia: the PACO prospective cohort study protocol.

BACKGROUND: Alzheimer's disease is characterised by a loss of cognitive function and behavioural problems as set out in the term "Behavioural and Psychological Symptoms of Dementia". These behavioural symptoms have heavy consequences for the patients and their families. A greater understanding of behavioural symptoms risk factors would allow better detection of those patients, a better understanding of crisis situations and better management of these patients. Some retrospective studies or simple observations suggested that personality could play a role in the occurrence of behavioural symptoms. Finally, performance in social cognition like facial recognition and perspective taking could be linked to certain personality traits and the subsequent risks of behavioural symptoms. We propose to clarify this through a prospective, multicentre, multidisciplinary study. Main Objective: -To assess the effect of personality and life events on the risk of developing behavioural symptoms. Secondary Objectives: -To evaluate, at the time of inclusion, the connection between personality and performance in social cognition tests; -To evaluate the correlation between performance in social cognition at inclusion and the risks of occurrence of behavioural symptoms; -To evaluate the correlation between regional cerebral atrophy, using brain Magnetic Resonance Imaging at baseline, and the risk of behavioural symptoms. METHODS/DESIGN: Study type and Population: Prospective multicentre cohort study with 252 patients with Alzheimer's disease at prodromal or mild dementia stage. The inclusion period will be of 18 months and the patients will be followed during 18 months. The initial evaluation will include: a clinical and neuropsychological examination, collection of behavioural symptoms data (Neuropsychiatric-Inventory scale) and their risk factors, a personality study using both a dimensional (personality traits) and categorical approach, an inventory of life events, social cognition tests and an Magnetic Resonance Imaging. Patients will be followed every 6 months (clinical examination and collection of behavioural symptoms data and risk factors) during 18 months. DISCUSSION: This study aims at better identifying the patients with Alzheimer's disease at high risk of developing behavioural symptoms, to anticipate, detect and quickly treat these disorders and so, prevent serious consequences for the patient and his caregivers. TRIAL REGISTRATION: ClincalTrials.gov: NCT01297140.

Evaluation of shearwave elastography for the characterisation of focal liver lesions on ultrasound.

OBJECTIVES: To determine the elasticity characteristics of focal liver lesions (FLLs) by shearwave elastography (SWE). METHODS: We used SWE in 108 patients with 161 FLLs and in the adjacent liver for quantitative and qualitative FLLs stiffness assessment. The Mann-Whitney test was used to assess the difference between the groups of lesions where a P value less than 0.05 was considered significant. RESULTS: SWE acquisitions failed in 22 nodules (14 %) in 13 patients. For the 139 lesions successfully evaluated, SWE values were (in kPa), for the 3 focal fatty sparings (FFS) 6.6 ± 0.3, for the 10 adenomas 9.4 ± 4.3, for the 22 haemangiomas 13.8 ± -5.5, for the 16 focal nodular hyperplasias (FNHs) 33 ± -14.7, for the 2 scars 53.7 ± 4.7, for the 26 HCCs 14.86 ± 10, for the 53 metastasis 28.8 ± 16, and for the 7 cholangiocarcinomas 56.9 ± 25.6. FNHs had significant differences in stiffness compared with adenomas (P = 0.0002). Fifty percent of the FNHs had a radial pattern of elevated elasticity. A significant difference was also found between HCCs and cholangiocarcinomas elasticity (P = 0.0004). CONCLUSIONS: SWE could be useful in differentiating FNHs and adenomas, or HCCs and cholangiocarcinomas by ultrasound.

Contrast-enhanced ultrasound: a new method for TIPS follow-up.

PURPOSE: To determine the diagnostic value of contrast-enhanced ultrasound (CEUS) for the detection of TIPS (transjugular intrahepatic portosystemic shunt) complications. MATERIALS AND METHOD: 67 cirrhotic patients who underwent TIPS between 2001 and 2008 were retrospectively reviewed. Sixty-two vascular examinations in 37 patients for suspicion of TIPS dysfunction based on the clinical or radiological criteria were analyzed and compared with the 62 related Doppler and CEUS examinations obtained previously. Abnormal CEUS was defined as poor opacification of the prosthesis compared to the native portal vein, stent stenosis, hepatic vein stenosis, and occlusion of the stent. RESULTS: Among the 62 vascular examinations, 56 were considered as pathologic, including: 20 occlusions, 25 stent stenoses, 9 hepatic vein stenoses, 1 arterial-TIPS fistula, and 1 strong flow stealing through a voluminous paraumbilical vein associated with a patent shunt. 50 were exactly correlated with a previous CEUS examination, including 20/20 occlusions (100%), 23/25 stent stenoses (91%), 5/9 hepatic vein stenoses (56%), 1/1 fistula (100%), and 1/1 strong flow stealing (100%). Two CEUS and 14 Doppler examinations were false negative. CONCLUSION: CEUS allows direct visualization of intra-prosthetic flow, with a qualitative and anatomic study, in addition to the Doppler examination. This is a new, simple, and effective technique for TIPS follow-up.

Accuracy of bedside bidimensional transcranial ultrasound versus tomodensitometric measurement of the third ventricle.

BACKGROUND AND PURPOSE: To evaluate the accuracy of transcranial duplex sonography (TCS) for measuring the diameter of the third ventricle (DTV) and the brain midline shift (MLS), as compared to cerebral CT. METHODS: Single-center retrospective study including 177 patients admitted to the neurological intensive care unit (NICU). We studied the correlation between TCS and CT measurements of DTV and MLS using a Bland-Altman analysis. The best threshold of DTV to diagnose acute hydrocephalus was evaluated with a receiver operating characteristic (ROC) analysis. RESULTS: We analyzed 177 pairs of CT-TCS measurements for DTV and 165 for MLS. The mean time interval between CT and TCS was 87 ± 73 minutes. Median DTV measurement on CT was 4 ± 3 mm, and 5 ± 3 mm by TCS. Median MLS on CT was 2 ± 3 mm, and 2 ± 4 mm by TCS. The Pearson correlation coefficient (r2 ) was .96 between TCS and CT measurements (p < .001). The Bland-Altman analysis found a proportional bias of 0.69 mm for the DTV with a limit of agreement ranging between -3.04 and 2.53 mm. For the MLS, the proportional bias was 0.23 mm with limits of agreements between -3.5 and 3.95. The area under the ROC curve was .97 for the detection of hydrocephalus by DTV on TCS, with a best threshold of 5.72 mm (Sensitivity [Se] = 92% Specificity [Sp] = 92.1%). CONCLUSIONS: TCS seems to be a reliable and accurate bedside technique for measuring both DTV and MLS, which might allow detection of acute hydrocephalus among NICU patients.

Comparison of Instrumental Activities of Daily Living assessment by face-to-face or telephone interviews: a randomized, crossover study.

BACKGROUND: The functional autonomy assessment is essential to manage patients with a neurodegenerative disease, but its evaluation is not always possible during a consultation. To optimize ambulatory autonomy assessment, we compared the Lawton Instrumental Activities of Daily Living (IADL) questionnaire collected by telephone and face-to-face interviews. METHODS: A randomized, crossover study was carried out among patients attending a memory clinic (MC). The IADL questionnaire was collected for patients during telephone and face-to-face interviews between nurses and patients' caregivers. The agreement between the two methods was measured using the proportion of participants giving the same response, Cohen's kappa, intraclass correlation (ICC) coefficient, and Bland and Altman method. The associations between patients' characteristics, events occurring between the two assessments, and agreement were assessed. RESULTS: Among the 292 patients (means ± SD age 81.5 ± 7, MMSE 19.6 ± 6, 39.7% with major neurocognitive disorders) analyzed, the proportion of agreement between the two modes was 89.4% for the total IADL score. Weighted kappa coefficient was 0.66 and ICC score was 0.91 for total IADL score. The mean difference between the IADL score by telephone or face-to-face was 0.32. Overall, 96.9% of measures lay within the 95% limits of agreement. The occurrence of fall was less likely associated with the probability to lie within the 95% limits of agreement (OR = 0.07 [0.02-0.27]). CONCLUSION: The administration of IADL by telephone with the caregiver appears to be an acceptable method of assessment for MC patients compared to face-to-face interview. The events such as falls which could occur in a time close to the evaluation should be reported. STUDY REGISTRATION: ClinicalTrials.gov, NCT02654574. Retrospectively registered: 13 January 2016.

Neuroticism-Withdrawal and Neuroticism-Volatility Differently Influence the Risk of Neuropsychiatric Symptoms in Alzheimer's Disease.

BACKGROUND: Neuroticism is recognized as the personality domain that is most strongly associated with behavioral and psychological symptoms (BPS) of Alzheimer's disease (AD). Two sub-components of neuroticism have been recently isolated. Neuroticism-withdrawal (N-withdrawal) refers to the tendency to internalize negative emotion, whereas neuroticism-volatility (N-volatility) reflect the predisposition to externalize negative emotions. OBJECTIVE: The objective of the current study was to investigate the specific influence of these two sub-components of neuroticism on BPS. METHODS: One hundred eighty-seven patients with prodromal or mild AD were drawn from the PACO study (Personalité Alzheimer COmportement). Neuroticism and its facets were assessed at baseline using the NEO-PI-R inventory. N-withdrawal and N-volatility were isolated using a principal component analysis led on the six facets composing neuroticism. BPS were measured with the short version of Neuropsychiatric Inventory (NPI-Q) and collected at baseline, then every 6 months over an 18-month follow-up. Linear mixed-effect analyses were conducted to investigate the association between N-withdrawal, N-volatility, and the severity of BPS over the follow-up. RESULTS: Mean age of the participant was 79.2±6.5; 59% were female; mean MMSE was 24.5±2.5. Both N-volatility and N-withdrawal were related with the NPI-Q (p < 0.001; p = 0,004). N-withdrawal was positively associated with anxiety (p = 0.001) and depression (p = 0.002), while N-volatility was positively related to delusions (p = 0.004), agitation/aggression (p < 0.001), irritability/volatility (p = 0.037), and apathy (p = 0.021). CONCLUSION: The present study demonstrates that N-volatility and N-withdrawal influence the risk of developing BPS in a different way. These results highlight the relevance of considering sub-components of neuroticism when studying links between personality and BPS.

Brain Volume Predicts Behavioral and Psychological Symptoms in Alzheimer's Disease.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are frequent and troublesome for patients and caregivers. Considering possible preventive approaches, a better understanding of underlying neural correlates of BPSD is crucial. OBJECTIVE: The aim is to assess whether brain regional volume predicts behavioral changes in mild AD. METHODS: This work took part from the PACO study, a multicenter and prospective study that included 252 patients with mild AD from 2009 to 2014. Fifty-three patients were retained. Forty healthy matched control subjects from the ADNI cohort were included as controls. Voxel-based morphometry analysis was conducted to assess regional brain volume using baseline MRI scans as a predictor of future behavioral changes over a period of 18 months. Behavior was assessed at baseline and longitudinally at 6-month intervals using the shortened form of the Neuropsychiatric Inventory (NPI). RESULTS: The volume of 23 brain structures in frontal, temporal, parietal, occipital, subcortical regions and cerebellum predicted the evolution of NPI scores. Frontal volume was the most powerful predictor with frontal gyri, anterior cingulate cortex, and orbital gyri being particularly involved. CONCLUSION: To our knowledge, this is the first study assessing regional brain volumes as predictors of behavioral changes considered at earlier stages of AD. Up to 23 brain structures were associated with an increased risk of developing BPSD. Frontal lobe volume was the strongest predictor of future evolution of NPI. The involvement of multiple structures in the prediction of behavior suggests a role of the main large-scale networks involved in cognition.

Personality Traits are Related to Selective Cognitive Impairment in Early Alzheimer's Disease.

BACKGROUND: A link between personality traits and cognitive performance has been shown in normal adults and elderly individuals. Very few studies have evaluated this link in Alzheimer's disease (AD). OBJECTIVE: To better understand cognitive performance as regards to personality traits, our study was aimed to evaluate the role of premorbid personality on cognitive functioning in a population of patients presenting prodromal or mild AD. METHODS: 181 elderly with prodromal or mild AD participated in a cross-sectional, prospective cohort study. The participants completed a personality inventory and a neuropsychological battery exploring memory, attention, executive function, language, and praxis. Cognitive performance were compared according to the level of each personality trait, using multivariate MANOVA models. RESULTS: A higher level of neuroticism was associated with lower performance at similarities test (D = 9.49, p = 0.003), delayed Free and Cued Selective Reminding test (D = 5.22, p = 0.02), and digit span score (D = 7.99, p = 0.006). A higher level of openness was related to better performance at similarities (D = 4.33, p = 0.04), letter fluency (D = 11.45, p = 0.001), and category fluency test (D = 5.85, p = 0.02). Neuroticism interfered negatively with cognitive functioning at the prodromal stage; the association between openness and cognitive function was observed at both prodromal and mild AD stage. CONCLUSION: These results suggest that personality traits, in particular neuroticism and openness, modulate cognitive abilities in patients with early AD. These results encourage the development of stress management programs to prevent its negative effects on cognitive aging.

Does Personality Predict Behavioral and Psychological Symptoms of Dementia? Results from PACO Prospective Study.

BACKGROUND: Premorbid personality could play a role in the onset of behavioral and psychological symptoms (BPS) in Alzheimer's disease (AD) but prospective studies are lacking. OBJECTIVE: The present study aimed at prospectively assessing the influence of premorbid personality traits on BPS evolution in a population of patients with prodromal or mild AD. METHODS: We used a multicenter prospective cohort study of 237 patients followed-up for 18 months. The influence of personality traits on BPS evolution, measured with Neuropsychiatric Inventory (NPI), was assessed using linear mixed-effect models. RESULTS: A principal components analysis of the 12 NPI behavioral domains yielded five factors labelled as psychotic symptoms, affective symptoms, behavioral dyscontrol, apathy/appetite symptoms, and sleep disorders. During the follow-up, higher neuroticism was significantly associated with a higher progression of affective symptoms (p < 0.0001), apathy/appetite symptoms (p = 0.002), sleep disorders (p = 0.001) as well as global NPI scores (p < 0.0001). Greater conscientiousness was related to a lower evolution of psychotic (p = 0.002), affective (p = 0.02) and apathy/appetite symptoms (p = 0.02), and global NPI score (p < 0.0001). Higher openness was associated with lower affective symptoms evolution (p = 0.01). A significant relationship was found between higher extraversion, lower affective symptoms (p = 0.02), and higher behavioral dyscontrol (p = 0.04). CONCLUSION: The present analysis suggests that premorbid personality may influence the evolution of BPS in prodromal or mild AD. Given these results, it seems important to give more importance to personality assessment in early AD, in order to better identify and manage patients at risk of adverse behavioral changes.

Cone Beam CT Versus Multislice CT: Radiologic Diagnostic Agreement in the Postoperative Assessment of Cochlear Implantation.

OBJECTIVE: To evaluate the diagnostic concordance between multislice computed tomography (MSCT) and cone beam computed tomography (CBCT) in the early postoperative assessment of patients after cochlear implantation. STUDY DESIGN: Prospective, randomized, single-center, interventional, pilot study on the diagnostic performance of a medical device. SETTING: Tertiary referral center. PATIENTS: Patients aged over 18 years requiring a computed tomographic (CT) scan after cochlear implant surgery. INTERVENTIONS: Nine patients were implanted with electrode arrays from three different manufacturers, including one bilateral. High-resolution MSCT and CBCT were then performed, and two experienced radiologists blinded to the imaging modality evaluated the randomized images, twice. MAIN OUTCOME MEASURES: Concordance between MSCT and CBCT for assessing the scalar position (tympani or vestibuli) of the electrodes. Secondary outcome measures were also studied: length of the intracochlear electrode array, percentage of implanted cochlea, number of intracochlear electrodes, and radiation doses. RESULTS: There was a good agreement between both CT scanners in determining the scalar position and estimating the number of implanted electrodes and percentage of implanted cochlea. CBCT had a lower radiation exposure. CONCLUSIONS: The CBCT appears to be a useful tool for postoperative assessment of cochlear implanted adult patients and is comparable to the conventional scanner in determining the scalar position, with lower radiation exposure.

Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer's Disease.

Early Alzheimer's disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer's disease and behaviour), 39 patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions-happiness, fear, anger, and disgust-on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects' performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer's disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional ß-amyloid deposition, or transient overcompensation during early stages of Alzheimer's disease.

In Vivo response to compression of 35 breast lesions observed with a two-dimensional locally regularized strain estimation method.

The objective of this study was to assess the in vivo performance of our 2-D locally regularized strain estimation method with 35 breast lesions, mainly cysts, fibroadenomas and carcinomas. The specific 2-D deformation model used, as well as the method's adaptability, led to an algorithm that is able to track tissue motion from radiofrequency ultrasound images acquired in clinical conditions. Particular attention was paid to strain estimation reliability, implying analysis of the mean normalized correlation coefficient maps. For all lesions examined, the results indicated that strain image interpretation, as well as its comparison with B-mode data, should take into account the information provided by the mean normalized correlation coefficient map. Different trends were observed in the tissue response to compression. In particular, carcinomas appeared larger in strain images than in B-mode images, resulting in a mean strain/B-mode lesion area ratio of 2.59 ± 1.36. In comparison, the same ratio was assessed as 1.04 ± 0.26 for fibroadenomas. These results are in agreement with those of previous studies, and confirm the interest of a more thorough consideration of size difference as one parameter discriminating between malignant and benign lesions.

Impact of diffusion-weighted MR imaging on the characterization of small hepatocellular carcinoma in the cirrhotic liver.

PURPOSE: The purpose of this study was to determine whether or not adding diffusion-weighted magnetic resonance imaging (DWI) to conventional magnetic resonance (MR) imaging sequences improves the characterization of small hepatocellular carcinoma (HCC) (≤2 cm) in the setting of cirrhotic liver compared to conventional sequences alone. MATERIALS AND METHODS: A total of 62 cirrhotic liver patients with 82 nodules smaller than 2 cm in diameter were enrolled, and all lesions were pathologically confirmed. For the first reading session, which included precontrast T1- and T2-weighted images and T1 dynamic contrast-enhanced images, preindicated lesions by a study coordinator were characterized by two radiologists. They determined the confidence levels in consensus for the presence of small HCC into four grades. In another session, respiratory-triggered diffusion-weighted MR images (b factor=50, 400 and 800 s/mm(2)) were added to the previously reviewed images, and the same two radiologists again determined the confidence levels. The diagnostic performance of the combined DWI-conventional sequences set and the conventional sequences alone set was evaluated using receiver operating characteristic curves. Sensitivity and specificity values for characterizing small HCCs were also calculated. RESULTS: The area under the receiver operating characteristic curve for the second interpretation session (0.86) was significantly higher (P=.038) than that of the first session (0.76). The sensitivity was significantly increased from 75.7% to 87.8% by adding DWI to the conventional sequences (P=.015). No significant differences were observed for specificity values. CONCLUSION: Adding DWI to conventional imaging modalities improves the diagnosis of small HCCs in the cirrhotic liver in terms of diagnostic performance and sensitivity by increasing reader confidence.