Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

Beyond the amyloid cascade: An update of Alzheimer's disease pathophysiology.

Alzheimer's disease (AD) is a multi-etiology disease. The biological system of AD is associated with multidomain genetic, molecular, cellular, and network brain dysfunctions, interacting with central and peripheral immunity. These dysfunctions have been primarily conceptualized according to the assumption that amyloid deposition in the brain, whether from a stochastic or a genetic accident, is the upstream pathological change. However, the arborescence of AD pathological changes suggests that a single amyloid pathway might be too restrictive or inconsistent with a cascading effect. In this review, we discuss the recent human studies of late-onset AD pathophysiology in an attempt to establish a general updated view focusing on the early stages. Several factors highlight heterogenous multi-cellular pathological changes in AD, which seem to work in a self-amplifying manner with amyloid and tau pathologies. Neuroinflammation has an increasing importance as a major pathological driver, and perhaps as a convergent biological basis of aging, genetic, lifestyle and environmental risk factors.

Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study.

OBJECTIVES: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. METHODOLOGY: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). RESULTS: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. CONCLUSION: Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP. KEY POINTS: • Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.

Testing an Adapted Auditory Verbal Learning Test Paradigm for fMRI to Lateralize Verbal Memory in Patients with Epilepsy.

BACKGROUND AND PURPOSE: fMRI is a noninvasive tool for predicting postsurgical deficits in candidates with pharmacoresistant temporal lobe epilepsy. We aimed to test an adapted paradigm of the Rey Auditory Verbal Learning Test to evaluate differences in memory laterality indexes between patients and healthy controls and its association with neuropsychological scores. MATERIALS AND METHODS: We performed a prospective study of 50 patients with temporal lobe epilepsy and 22 healthy controls. Participants underwent a block design language and memory fMRI. Laterality indexes and the hippocampal anterior-posterior index were calculated. Language and memory lateralization was organized into typical and atypical on the basis of laterality indexes. A neuropsychological assessment was performed with a median time from fMRI of 8 months and was compared with fMRI performance. RESULTS: We studied 40 patients with left temporal lobe epilepsy and 10 with right temporal lobe epilepsy. Typical language occurred in 65.3% of patients and 90.9% of healthy controls (P = .04). The memory fMRI laterality index was obtained in all healthy controls and 92% of patients. The verbal memory laterality index was bilateral (24.3%) more frequently than the language laterality index (7.69%) in patients with left temporal lobe epilepsy. Atypical verbal memory was greater in patients with left temporal lobe epilepsy (56.8%) than in healthy controls (36.4%), and the proportion of bilateral laterality indexes (53.3%) was larger than right laterality indexes (46.7%). Atypical verbal memory might be associated with higher cognitive scores in patients. No relevant differences were seen in the hippocampal anterior-posterior index according to memory impairment. CONCLUSIONS: The adapted Rey Auditory Verbal Learning Test paradigm fMRI might support verbal memory lateralization. Temporal lobe epilepsy laterality influences hippocampal memory laterality indexes. Left temporal lobe epilepsy has shown a higher proportion of atypical verbal memory compared with language, potentially to memory functional reorganization.

Different clinical outcomes between cerebral amyloid angiopathy-related inflammation and non-inflammatory form.

OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.

Simulations of micro-sphere/shell 2D silica photonic crystals for radiative cooling.

Passive daytime radiative cooling has recently become an attractive approach to address the global energy demand associated with modern refrigeration technologies. One technique to increase the radiative cooling performance is to engineer the surface of a polar dielectric material to enhance its emittance at wavelengths in the atmospheric infrared transparency window (8-13 µm) by outcoupling surface-phonon polaritons (SPhPs) into free-space. Here we present a theoretical investigation of new surface morphologies based upon self-assembled silica photonic crystals (PCs) using an in-house built rigorous coupled-wave analysis (RCWA) code. Simulations predict that silica micro-sphere PCs can reach up to 73 K below ambient temperature, when solar absorption and conductive/convective losses can be neglected. Micro-shell structures are studied to explore the direct outcoupling of the SPhP, resulting in near-unity emittance between 8 and 10 µm. Additionally, the effect of material composition is explored by simulating soda-lime glass micro-shells, which, in turn, exhibit a temperature reduction of 61 K below ambient temperature. The RCWA code was compared to FTIR measurements of silica micro-spheres, self-assembled on microscope slides.

The role of neuropsychological assessment in adults with attention deficit/hyperactivity disorders.

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and/or impulsivity. While ADHD was initially recognized as a childhood syndrome, scientific evidence accumulated to indicate that a significant proportion of ADHD children continue to experience symptoms of ADHD in adulthood. Moreover, the question of ADHD diagnosis can arise in adult patients who were not diagnosed in childhood. Currently, the diagnosis of ADHD in adulthood is based on the revised criteria described for children. However, their application for adults may be difficult for many reasons including compensation and comorbid disorders. To date, no clinical, neuropsychological, biological or imaging marker is available for the diagnosis of ADHD. Considering that ADHD is based on a neuropsychological model, in this article we will examine the usefulness of neuropsychological testing in the diagnosis in adults. We will first present diagnostic criteria of ADHD and the limits of their application in adults. We will then detail the neuropsychological data available in adult ADHD and the French and international clinical recommendations for neuropsychological assessment. Finally, we will explore the predictive value of neuropsychological scores in the diagnosis of ADHD and discuss key methodological points and perspectives for clinical research.

Diagnosis clinical criteria of sport related concussion: Toward an operational criteria definition in France.

OBJECTIVE: An expert working group was set up at the initiative of the French Ministry of Sports with the objective of harmonising the management of sport related concussion (SRC) in France, starting with its definition and diagnosis criteria. RESULTS: Definition: A clinical definition in 4 points have been established as follows: Concussion is a brain injury: 1) caused by a direct or indirect transmission of kinetic energy to the head; 2) resulting in an immediate and transient dysfunction of the brain characterised by at least one of the following disorders: a) Loss of consciousness, b) loss of memory, c) altered mental status, d) neurological signs; 3) possibly followed by one or more functional complaints (concussion syndrome); 4) the signs and symptoms are not explained by another cause. Diagnosis criteria: In the context of the direct or indirect transmission of kinetic energy to the head, the diagnosis of concussion may be asserted if at least one of the following signs or symptoms, observed or reported, is present within the first 24hours and not explained by another cause: 1) loss of consciousness; 2) convulsions, tonic posturing; 3) ataxia; 4) visual trouble; 5) neurological deficit; 6) confusion; 7) disorientation; 8) unusual behaviour; 9) amnesia; 10) headaches; 11) dizziness; 12) fatigue, low energy; 13) feeling slowed down, drowsiness; 14) nausea; 15) sensitivity to light/noise; 16) not feeling right, in a fog; 17) difficulty concentrating. CONCLUSION: Sharing the same definition and the same clinical diagnostic criteria for concussion is the prerequisite for common rules of management for all sports and should allow the pooling of results to improve our knowledge of this pathology.

Interhemispheric distribution of amyloid and small vessel disease burden in cerebral amyloid angiopathy-related intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating presentation of cerebral amyloid angiopathy (CAA), but the mechanisms leading from vascular amyloid deposition to ICH are not well known. Whether amyloid burden and magnetic resonance imaging (MRI) markers of small vessel disease (SVD) are increased in the ICH-affected hemisphere compared to the ICH-free hemisphere in patients with a symptomatic CAA-related ICH was investigated. METHODS: Eighteen patients with CAA-related ICH and 18 controls with deep ICH who underwent brain MRI and amyloid positron emission tomography using 18 F-florbetapir were prospectively enrolled. In each hemisphere amyloid uptake using the standardized uptake value ratio and the burden of MRI markers of SVD including cerebral microbleeds, chronic ICH, cortical superficial siderosis, white matter hyperintensities and lacunes were evaluated. Interhemispheric comparisons were assessed by non-parametric matched-pair tests within each patient group. RESULTS: Amyloid burden was similarly distributed across the brain hemispheres in patients with CAA-related ICH (standardized uptake value ratio 1.11 vs. 1.12; P = 0.74). Cortical superficial siderosis tended to be more common in the ICH-affected hemisphere compared to the ICH-free hemisphere (61% vs. 33%; P = 0.063). Other MRI markers of SVD did not differ across brain hemispheres. In controls with deep ICH, no interhemispheric difference was observed either for amyloid burden or for MRI markers of SVD. CONCLUSIONS: Brain hemorrhage does not appear to be directly linked to amyloid burden in patients with CAA-related ICH. These findings provide new insights into the mechanisms leading to hemorrhage in CAA.

Development of a clinical-dermoscopic model for the diagnosis of urticarial vasculitis.

The clinical criteria for the diagnosis of urticarial vasculitis lack accuracy, according to previous studies. The aim of the study was to assess the accuracy of a clinical and a clinical-dermoscopic model for the differential diagnosis of chronic spontaneous urticaria (CSU) and urticarial vasculitis (UV). Dermoscopic images of lesions with histopathologically confirmed diagnosis of CSU and UV were evaluated for the presence of selected criteria (purpuric patches/globules (PG) and red linear vessels). Clinical criteria of CSU and UV were also registered. Univariate and adjusted odds ratios were calculated. Multivariate regression analyses were conducted separately for clinical variables (clinical diagnostic model) and for both clinical and dermoscopic variables (clinical-dermoscopic diagnostic model). 108 patients with CSU and 27 patients with UV were included in the study. The clinical-dermoscopic model notably showed higher diagnostic sensitivity than the clinical approach (63% vs. 44%). Dermoscopic purpuric patches/globules (PG) was the variable that better discriminated UV, increasing by 19-fold the odds for this diagnosis. In conclusion, dermoscopy helps the clinical discrimination between CSU and UV. The visualization of dermoscopic PG may contribute to optimize decisions regarding biopsy in patients with urticarial rashes.

Age effects on the neural processing of object-context associations in briefly flashed natural scenes.

In daily life, fast visual recognition of surrounding objects is facilitated through context-based expectations. However the ability to rapidly and accurately recognize unexpected stimuli in a given environment is also crucial and this ability is impaired with age. The present fMRI study aimed at comparing in young and older adults the neural correlates of fast object processing. Patterns of cerebral activity were investigated in response to briefly-presented (100 ms) congruent and incongruent natural scenes. Participants were slower and less accurate when categorizing objects in incongruent relative to congruent contexts. This behavioral cost was notably more pronounced in the older group. Height and multivariate patterns of fMRI activity in context-selective regions were equivalent in both age groups, suggesting preserved processing of coarse scene features in older participants. Incongruent scenes elicited additional activity in the parahippocampal gyrus that possibly reflected simultaneous activation of rarely co-occurring neural representations. Contextual effects were observed in object-selective cortex for the young group only, and may be driven by detection of mismatch between actually perceived and previously-experienced associations. In the older group exclusively, increased bilateral prefrontal and left fusiform activity in response to incongruent scenes was observed. However this supplemental activity was not found to efficiently contribute to improve task performance in difficult visual conditions. Altogether these results suggest age-related changes in the interaction between object- and context-processing pathways, that may subserve impairment in fast identification of unexpected objects in natural scenes.

Discourse macrolinguistic impairment as a marker of linguistic and extralinguistic functions decline in early Alzheimer's disease.

BACKGROUND: Alzheimer's disease is characterized by macrolinguistic changes. This decline is often analyzed with quantitative scales. AIMS: To analyze discourse production in early Alzheimer's disease (AD) and to identify qualitative markers of macrolinguistic decline. METHODS & PROCEDURES: We analyzed macrolinguistic features of a clinical narrative task along with patients' cognitive changes. To do so, 17 early AD participants and 17 healthy controls were recruited and given a full neuropsychological and language assessment. Narrative discourses produced during the language assessment were transcribed and macrolinguistic features were qualitatively analyzed (i.e., local and global coherence marks and discourse informativeness). Inter-group comparison was complemented by intra-group correlation. As some inter-group comparisons revealed the existence of subgroups of patients, permutation tests were used to investigate how these subgroups differed vis-à-vis cognitive measures. OUTCOMES & RESULTS: Overall, the results indicate that AD participants presented declines in informativeness and global coherence, correlated with declines in memory and executive functions. Permutation tests showed that participants with AD producing referential errors or misinterpretations had a deeper lexical-executive decline and a lower Mini-Mental State Evaluation (MMSE). CONCLUSIONS & IMPLICATIONS: This study shows that two clinically relevant, qualitative signs differ in discourse production between typical ageing and early AD, namely information units and modalizing discourse. It also shows that macrolinguistic assessment is a useful tool for revealing impaired communication and cognition in early AD. Although lexical processing decline probably contributes to patients' macrolinguistic impairment, implications of extralinguistic functioning should be further investigated.

What happens when nothing happens? An investigation of pauses as a compensatory mechanism in early Alzheimer's disease.

Lexical-semantic impairment is one of the earliest symptoms of Alzheimer's disease (AD) and is usually examined by single word processing tasks. During speech production, pauses are often investigated as a hallmark of a patient's lexical-semantic decline. In the current study, we put forward the hypothesis that pauses reflect different processes according to the type of discourse. We believe that lexical and semantic impairment would predict a patient's pause frequency in a picture-based narrative (PBN) while anterograde memory would predict a patient's pause frequency in a memory-based narrative (MBN). To demonstrate this, we recruited 17 early AD patients and 17 matched controls. They underwent a full neuropsychological and language assessment and two narrative production assessments. We compared pause duration and frequency in the AD participants' and healthy controls' PBN and MBN. A multiple regression model was used in each narrative and in each group individually to assess the relationship between cognitive processes and pause frequency. Our results show that participants with AD produced more pauses in the PBN only. The frequency was predicted by semantic fluency performance with which it was positively correlated, contrary to what was expected. In the MBN, pause frequency in the AD participants was positively correlated with and predicted by their memory performance. We then examined the neuroanatomical correlates of pause frequency in the AD participants. Considering the PBN, pause frequency was also positively correlated with the grey matter density of the anterior temporal lobe. These findings suggest that patients use pauses as compensatory mechanisms in the earliest stages of AD. Pauses therefore may reflect the time required for the compensation and the realisation of a weak process depending on the narrative task and should be considered as a positive sign.

Serotonin Selective Reuptake Inhibitors (SSRIs) and Stroke.

PURPOSE OF REVIEW: The interest in SSRIs after stroke has increased in the past few years, with better knowledge of post-stroke depression and with the demonstrated capacity of some SSRIs to act on the functional recovery of non-depressed subjects. RECENT FINDINGS: Arguments for the action of SSRIs in favour of post-stroke neurological function recovery have improved through new elements: basic science and preclinical data, positive clinical trials and repeated series of stroke patient meta-analysis, and confirmation of favourable safety conditions in post-stroke patients. Global coherence is appearing, showing that SSRIs improve stroke recovery in non-depressed patients when given for 3 months after the stroke, with highly favourable safety conditions and a favourable benefit/risk ratio. Large series are still needed.

Cognitive complaint in early Parkinson's disease: A pilot study.

BACKGROUND: Subjective cognitive complaint (SCC) is a criterion recommended by the Movement Disorder Society (MDS) task force for the diagnosis of mild cognitive impairment (MCI). Until now there were few specific tools for detecting SCC in PD. We sought to develop a new tool to assess SCC specifically dedicated for PD. MATERIALS AND METHODS: We set a group of experts in movements disorders and neurocognition to develop an easy-to-use tool based on a visual analogue scale (VAS) for five cognitive domains: memory, executive functions, spatial orientation, attention, and language. We use it to assess SCC twice (at a one-month interval) in PD patients with disease duration of less than 5 years. Comprehensibility of the VAS was assessed. Controls were assessed with the same VAS. Patients with PD also underwent neuropsychological testing. RESULTS: VAS was easily understandable by the 70 patients with PD. We found significant SCC for the patients with PD vs controls in three cognitive domains: executive functions (1.7 ± 1.9 vs 0.8 ± 1.1; P < .001), language (2.3 ± 2.5 vs 1.0 ± 1.3, P < .001), and attention (2.1 ± 2.2 vs 1.2 ± 1.2; P < .01). Reproducibility between the two evaluations of patients with PD was good. There was no relationship between SCC and the results of neuropsychological testing. CONCLUSIONS: SCC seems to appear early in PD, in three cognitive domains (executive functions, language, and attention), and VAS might be a good way to detect SCC in PD, but need to be validated.

Cortical superficial siderosis and acute convexity subarachnoid hemorrhage in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Acute convexity subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS) are neuroimaging markers of cerebral amyloid angiopathy (CAA) that may arise through similar mechanisms. The prevalence of cSS in patients with CAA presenting with acute cSAH versus lobar intracerebral hemorrhage (ICH) was compared and the physiopathology of cSS was explored by examining neuroimaging associations. METHODS: Data from 116 consecutive patients with probable CAA (mean age, 77.4 ± 7.3 years) presenting with acute cSAH (n = 45) or acute lobar ICH (n = 71) were retrospectively analyzed. Magnetic resonance imaging scans were analyzed for cSS and other imaging markers. The two groups' clinical and imaging data were compared and the associations between cSAH and cSS were explored. RESULTS: Patients with cSAH presented mostly with transient focal neurological episodes. The prevalence of cSS was higher amongst cSAH patients than amongst ICH patients (88.9% vs. 57.7%; P < 0.001). In multivariable logistic regression analysis, focal [odds ratio (OR) 6.73; 95% confidence interval (CI) 1.75-25.81; P = 0.005] and disseminated (OR 11.68; 95% CI 3.55-38.35; P < 0.001) cSS were independently associated with acute cSAH, whereas older age (OR 0.93; 95% CI 0.87-0.99; P = 0.025) and chronic lobar ICH count (OR 0.45; 95% CI 0.25-0.80; P = 0.007) were associated with acute lobar ICH. CONCLUSIONS: Amongst patients with CAA, cSS is independently associated with acute cSAH. These findings suggest that cSAH may be involved in the pathogenesis of the cSS observed in CAA. Longitudinal studies are warranted to assess this potential causal relationship.

Cerebral amyloid angiopathy-related cognitive impairment: The search for a specific neuropsychological pattern.

Cerebral amyloid angiopathy is diagnosed in stroke units after lobar intracerebral hemorrhage. CAA can also be diagnosed in memory clinics when patients are referred for cognitive impairment assessment, and may be a reason for admission to emergency or neurology departments because of rapidly progressive cognitive or neurological decline, or a transient focal neurological episode. CAA may even be observed in older community-dwelling individuals. Neuropsychological impairment in CAA has been described over the past 20 years. The symptoms most commonly reported are perceptual speed, episodic memory, semantic memory, attention and executive function, and global cognitive impairments. Psychiatric symptoms, such as personality changes, behavioral disturbances and depression, have been more recently described. CAA is also a risk factor for the development of dementia, and its relationship with Alzheimer's disease has been demonstrated in post-mortem studies. Yet, despite the increase in literature on CAA-related cognitive and psychiatric symptoms, the specific characteristics of symptoms in CAA are difficult to assess because of the substantial prevalence of comorbidities such as small vessel disease due to high blood pressure, Lewy body disease and, of course, AD, all of which act as important confounding factors. Also, within the entity of CAA itself, the additive and perhaps synergistic effects of each lesion on cognition remain to be assessed. In the present paper, the focus is on the latest evidence of neuropsychological impairment observed in CAA patients, and the emergence of a possible specific neuropsychological profile due to CAA is also discussed.