Behavioral and Psychological Symptoms that Predict Cognitive Decline or Impairment in Cognitively Normal Middle-Aged or Older Adults: a Meta-Analysis.

Epidemiological studies have revealed that behavioral and psychological (or non-cognitive) symptoms are risk factors for cognitive decline in older adults. This study aimed to systematically review the literature and determine which behavioral and psychological symptoms are most predictive of future cognitive decline among individuals with no pre-existing cognitive impairments. The selected studies included middle-aged or older adults without cognitive impairments. The predictors were assessed using behavioral and psychological questionnaires, or diagnostic interviews, to identify non-cognitive symptoms or psychiatric clinical conditions. The follow-up period was at least one year, and the design of the selected studies was either retrospective or prospective. This study compared individuals with and without non-cognitive manifestations and resulted in one of three outcomes: (a) a score change on a cognitive measure, (b) a diagnosis of mild cognitive impairment, or (c) a diagnosis of Alzheimer's disease or dementia. Four online databases were searched for eligible studies from the database inception to January 17, 2017: MEDLINE (PubMed), Embase (OVID), PsycINFO, and Web of Science. Pooled effect sizes were estimated using a random-effect model. Higgins I2, the Q statistic, and tau-squared were used to quantify the observed heterogeneity between the studies. Results indicate that depression and sleep duration (long and short) were the most consistent associations between behavioral or psychological symptoms and cognitive decline. This meta-analysis supports the need to assess behavioral and psychological symptoms in cognitively intact older adults to identify those who are at risk for cognitive decline.

Detecting the Cognitive Prodrome of Dementia in Parkinson's Disease.

BACKGROUND: More than 75% of Parkinson's disease (PD) patients will develop dementia. Previous studies on the cognitive predictors of dementia in PD had some methodological limitations and the cognitive tests identified as good predictors vary greatly. OBJECTIVE: This prospective cohort study aims to identify the optimal cognitive predictors of dementia in PD using complementary statistical methods. METHODS: Eighty PD patients without dementia underwent polysomnographic recording, a neurological examination, and a complete neuropsychological assessment at baseline. They were then followed for a mean of 4.3 years. Baseline group comparisons and survival analyses were used to identify optimal cognitive predictors. Moreover, patients who developed dementia were pair-matched at baseline according to age, sex, and education to healthy controls (2 : 1), and receiver operating characteristic curves were calculated for cognitive tests. RESULTS: At follow-up, 23 patients (29%) developed dementia. PD patients who developed dementia had poorer baseline performance and a higher proportion of clinically impaired performance on several cognitive tests. Impaired baseline performance on the Block Design subtest was the best independent predictor of dementia (HR = 8). Moreover, the Trail Making Test part B (time) and Verbal Fluency (semantic) had the best psychometric properties (area under the curve >0.90) for identifying PD patients at risk of dementia. CONCLUSION: The present study identified three cognitive tests as the most accurate to detect individuals with PD at high risk of developing dementia.

Normative data for the Clock Drawing Test for French-Quebec mid- and older aged healthy adults.

OBJECTIVE: The Clock Drawing Test (CDT) is frequently used to screen for cognitive impairment, however, normative data for Rouleau et al.'s scoring system are scarce. The present study aims to provide norms for Rouleau et al.'s scoring system that are tailored to Quebec French-speaking mid- and older aged healthy adults. METHODS: Six researchers from various research centers across the Province of Quebec (Canada) sent anonymous data for 593 (391 women) healthy community-dwelling volunteers (age range: 43-93 years; education range: 5-23 years) who completed the CDT 'drawing on command' version. This command version (setting the clock hands to 11:10, without a pre-drawn circle) was administrated as part of a more extensive neuropsychological assessment, or along with cognitive screening instruments. Each drawn clock was scored according to the quantitative criteria set by Rouleau et al.'s scoring system. RESULTS: CDT scores were significantly correlated with age (r(592) = -.132, p = .001) and years of education (r(592) = .116, p = .005), but not with sex (r(592) = .065, p = .112). Since data were skewed towards higher test scores, the percentiles method was used for analysis. Percentile ranks stratified by age and education are presented. CONCLUSION: These normative data for Rouleau et al.'s scoring system will contribute towards adequately screening for cognitive decline in Quebec French-speaking healthy adults, by also taking into account individual characteristics such as age and education.

How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder.

OBJECTIVE: We describe the progression of cognitive decline and identify the predictive values of cognitive tests in three groups of REM sleep behavior disorder (RBD) patients classified at their last follow-up as having Parkinson's disease (PD), dementia with Lewy bodies (DLB), or still-idiopathic. METHODS: Patients (n = 109) underwent polysomnographic, neurological, and neuropsychological assessments. We used linear mixed-model analyses to compare the progression of cognitive test performance between the three groups over a 3-year prodromal period, and performed linear regressions for a 6-year prodromal period. We compared the proportions of patients with clinically impaired performance (z scores < -1.5). DLB patients were pair-matched according to age, sex, and education to healthy controls (2:1 ratio), and receiver operating characteristic curves were performed to identify the psychometric properties of cognitive tests to predict dementia. RESULTS: At follow-up, 38 patients (35%) developed a neurodegenerative disorder: 20 had PD and 18 DLB. Cognitive performance changes over time were strongly associated with later development of dementia. Clear deficits in attention and executive functions were observed 6 years before diagnosis. Verbal episodic learning and memory deficits started later, deviating from normal approximately 5 to 6 years and becoming clinically impaired at 1 to 2 years before diagnosis. Visuospatial abilities progressed variably, with inconsistent prodromal latencies. The Trail Making Test (part B), Verbal Fluency (semantic), and Rey Auditory-Verbal Learning Test (total, immediate, and delayed recalls) were the best predictors for dementia (area under the curve = 0.90-0.97). INTERPRETATION: Prodromal DLB is detectible up to 6 years before onset. For clinical utility, the Trail Making Test (part B) best detects early prodromal dementia stages, whereas Verbal Fluency (semantic) and verbal episodic learning tests are best for monitoring changes over time. Ann Neurol 2018;83:1016-1026.

Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder.

OBJECTIVE: To investigate cortical and subcortical gray matter abnormalities underlying cognitive impairment in patients with REM sleep behavior disorder (RBD) with or without mild cognitive impairment (MCI). METHODS: Fifty-two patients with RBD, including 17 patients with MCI, were recruited and compared to 41 controls. All participants underwent extensive clinical assessments, neuropsychological examination, and 3-tesla MRI acquisition of T1 anatomical images. Vertex-based cortical analyses of volume, thickness, and surface area were performed to investigate cortical abnormalities between groups, whereas vertex-based shape analysis was performed to investigate subcortical structure surfaces. Correlations were performed to investigate associations between cortical and subcortical metrics, cognitive domains, and other markers of neurodegeneration (color discrimination, olfaction, and autonomic measures). RESULTS: Patients with MCI had cortical thinning in the frontal, cingulate, temporal, and occipital cortices, and abnormal surface contraction in the lenticular nucleus and thalamus. Patients without MCI had cortical thinning restricted to the frontal cortex. Lower patient performance in cognitive domains was associated with cortical and subcortical abnormalities. Moreover, impaired performance on olfaction, color discrimination, and autonomic measures was associated with thinning in the occipital lobe. CONCLUSIONS: Cortical and subcortical gray matter abnormalities are associated with cognitive status in patients with RBD, with more extensive patterns in patients with MCI. Our results highlight the importance of distinguishing between subgroups of patients with RBD according to cognitive status in order to better understand the neurodegenerative process in this population.

Screening for prodromal Parkinson's disease in the general community: a sleep-based approach.

OBJECTIVE/BACKGROUND: Neuroprotective therapy for Parkinson's disease (PD) is most likely to be effective if provided in its prodromal stages. However, identifying prodromal PD is difficult because PD is relatively uncommon, and most markers are nonspecific. Rapid eye movement (REM) sleep behavior disorder (RBD) is by far the strongest clinical marker of prodromal PD, but most patients do not seek out medical attention. Developing an efficient way of diagnosing RBD from the general community may be the most practical method to detect prodromal PD. METHODS: We developed a screening strategy that began with a newspaper advertisement containing a single-question screen for RBD. All screen-positive subjects underwent an interview based on the Innsbruck RBD inventory aimed to optimize the positive predictive value. Those who passed both screens underwent confirmatory polysomnography. The proportion of screened RBD patients who met the International Parkinson and Movement Disorder Society (MDS) criteria for prodromal PD was assessed. A broad array of clinical markers of neurodegeneration was compared between newspaper-screened RBD patients and 130 RBD patients clinically referred to the sleep center. RESULTS: Of 111 RBD-screen-positive participants, 40 (36%) passed the secondary screen, and 29 underwent full polysomnography. Of these 29 patients, 19 were ultimately proven to have RBD (PPV = 66%), 12 (63%) of whom met the criteria for prodromal PD. Compared to patients referred to the sleep center, newspaper-screened patients had similar age, sex, olfaction, autonomic function, and color vision. However, motor and cognitive assessments were slightly better in newspaper-screened patients. CONCLUSIONS: A multistep screening approach using RBD screening questionnaires and telephone follow-up can efficiently identify prodromal PD in the general community.

Normative data for phonemic and semantic verbal fluency test in the adult French-Quebec population and validation study in Alzheimer's disease and depression.

OBJECTIVE: Verbal fluency tasks are principally used to assess lexical access and have shown usefulness for differential diagnosis. The purpose of Study 1 was to provide normative data in the adult French-Quebec population (Canada) for semantic verbal fluency (animals), for two sets of phonemic verbal fluency (TNP and PFL), and for letter P alone (60 seconds per category/letter). The objectives of Study 2 were to establish the diagnostic and predictive validity of the present tasks and normative data in Alzheimer's disease (AD) and major depressive episode (MDE). METHOD: The normative sample consisted of 932 participants aged 19-91 years. Based on multiple linear regressions, equations to calculate Z-scores were provided. To assess validity, performance of 62 healthy participants was compared to 62 participants with AD and 41 with MDE aged over 50. RESULTS: Age and education, but not gender, predicted performance on each verbal fluency task. Healthy adults aged 50 and younger had a better performance on semantic than phonemic verbal fluency. In comparison to MDE, AD participants had lower performance on animals and TNP, but not on letter P. Ninety percent of people with a Z-score ≤ -1.50 on semantic verbal fluency had AD and the global accuracy was 76.6%. Test-retest reliability over one year was high for both animals (r = .711) and TNP (r = .790) in healthy older participants, but dropped for animals in people with AD (r = .493). CONCLUSIONS: These data will strengthen accurate detection of verbal fluency deficits in French-Quebec adults.

Evaluating Decision-Making: Validation and Regression-Based Normative Data of the Judgment Assessment Tool.

OBJECTIVE: This study presents the results of the development and validation of the Judgment Assessment Tool (JAT). The JAT measures two core aspects of judgment, namely generation of solutions (G) and assessment of options (A), the two first stages of decision-making process. METHOD: During the test development phase (study 1), a preliminary version of the JAT was evaluated by 14 experts and tested on 30 healthy controls (HC). One hundred and twenty HC (20-84 years old) and 24 participants with mild Alzheimer's disease (AD) were subsequently tested on the final version of the JAT (study 2). HC participants aged 60 and over and AD participants underwent a neuropsychological evaluation. RESULTS: The internal consistency of the final version of the JAT assessed by Cronbach's a was 0.71 for the HC group and 0.85 for the AD group. Performance on the JAT was normally distributed both in the HC and AD groups. The test correlated with abstract reasoning, verbal fluency, and working memory. Results revealed adequate test-retest reliability and excellent interrater reliability (k coefficient was 0.92 for the G section and 0.93 for the A section). Demographically adjusted normative data were generated based on a regression analysis and results showed that AD participants performed worse than HC with a large effect size (Cohen's d = 1.79). CONCLUSION: Overall, these results provide evidence of the reliability and strong construct validity of the JAT to evaluate judgment.

Neuropsychological performance before and after partial or complete insulectomy in patients with epilepsy.

Resection of the insular cortex is becoming more frequent as it is increasingly recognized that a nonnegligible proportion of surgical candidates with drug-resistant epilepsy have an epileptogenic zone that involves the insula. In the last decades, however, the insula has been proposed to be involved in several neuropsychological functions, and there is a lack of documentation on whether partial or complete insulectomy results in permanent cognitive impairments in this clinical population. In this study, we conducted standard preoperative and postoperative neuropsychological assessments in 18 patients undergoing epilepsy surgery that included the removal of the insula in the right (n=13) or the left (n=5) hemisphere. Postoperative testing was conducted at least five months after surgery. Cognitive impairments were common and heterogeneous prior to surgery, with language and verbal memory impairments being especially frequent among patients in whom epileptic seizures originated from the left hemisphere. After surgery, declines and improvements occurred on a variety of outcomes, although new deficits were relatively infrequent among patients who had obtained normal performance at baseline. Statistical comparisons between preoperative and postoperative assessments revealed significant deterioration of only one outcome - the color naming condition of the Stroop test - which relies on oro-motor speed and lexical access. These findings suggest that partial or complete resection of the insular cortex in patients with drug-refractory epilepsy can be conducted without major permanent neuropsychological impairments in a vast majority of patients. However, small decrements in specific cognitive functions can be expected, which should also be taken into account when considering the surgical option in this clinical population.

Gender attribution and gender agreement in French Williams syndrome.

Previous studies on grammatical gender in French individuals with Williams syndrome (WS) have led to conflicting findings and interpretations regarding keys abilities--gender attribution and gender agreement. New production data from a larger WS sample (N=24) showed that gender attribution scores in WS participants exactly mirrored those of controls: all groups overwhelmingly relied on the masculine as the default gender. WS participants' agreement scores were far lower than those of CA-controls though not significantly below those of MA-controls. They also did not improve with age, which might suggest a permanent disability in this area.