Global Cognitive Impairment Research Articles

Higher white matter hyperintensity lesion load is associated with reduced long-range functional connectivity.

Cerebral small vessel disease is a common disease in the older population and is recognized as a major risk factor for cognitive decline and stroke. Small vessel disease is considered a global brain disease impacting the integrity of neuronal networks resulting in disturbances of structural and functional connectivity. A core feature of cerebral small vessel disease commonly present on neuroimaging is white matter hyperintensities. We studied high-resolution resting-state EEG, leveraging source reconstruction methods, in 35 participants with varying degree of white matter hyperintensities without clinically evident cognitive impairment in an observational study. In patients with increasing white matter lesion load, global theta power was increased independently of age. Whole-brain functional connectivity revealed a disrupted network confined to the alpha band in participants with higher white matter hyperintensities lesion load. The decrease of functional connectivity was evident in long-range connections, mostly originating or terminating in the frontal lobe. Cognitive testing revealed no global cognitive impairment; however, some participants revealed deficits of executive functions that were related to larger white matter hyperintensities lesion load. In summary, participants without clinical signs of mild cognitive impairment or dementia showed oscillatory changes that were significantly related to white matter lesion load. Hence, oscillatory neuronal network changes due to white matter lesions might act as biomarker prior to clinically relevant behavioural impairment.

Moderate-to-Severe Obstructive Sleep Apnea and Cognitive Function Impairment in Patients with COPD.

PurposePrior studies have indicated that patients with chronic obstructive pulmonary disease (COPD) exhibit significant cognitive defects on neuropsychological testing. Obstructive sleep apnea (OSA) is common in patients with COPD and is associated with reduced cognitive function; however, the combined impact of these two conditions on cognitive function is unknown. The aim of the study was to investigate the impact of OSA on cognitive impairment in patients with COPD.MethodsSixty-five stable COPD patients aged over 60 years underwent overnight polysomnography (PSG). Global cognitive functions were evaluated using the Mini-Mental State Examination (MMSE).ResultsCompared to patients with COPD alone, patients with both COPD and OSA performed worse on the MMSE (25.5±2.9 vs 23.5±3.2; p=0.01) and were more likely to be at risk for developing dementia based on the MMSE score (MMSE≤24) (31% vs 66%; p<0.01), independent of key demographic, educational and medical variables known to affect cognitive function in COPD. COPD patients with an apnea hypopnea index (AHI) of ≥30 events/h had lower MMSE scores than those with an AHI of <15 events/h. In addition to age and education level, the severity of nocturnal intermittent hypoxia is an independent predictor of the risk of dementia in patients with COPD (OR=1.24, 95% CI 1.04–1.48, p = 0.02).ConclusionThe current findings indicate that patients with COPD with comorbid OSA may be at greater risk for global cognitive impairment relative to patients with COPD alone. The mechanisms underlying the exaggerated cognitive dysfunction seem to be related to intermittent hypoxia. Further work is needed to understand the impact of OSA on the specific domains of cognitive impairment and the therapeutic implications of OSA in COPD.

S63. CLINICAL AND DEVELOPMENTAL CHARACTERISTICS OF COGNITIVE SUBGROUPS IN A TRANSDIAGNOSTIC SAMPLE OF SCHIZOPHRENIA, SCHIZOAFFECTIVE DISORDER AND BIPOLAR DISORDER

BackgroundEvidence suggests that neurocognitive dysfunction is a transdiagnostic feature of individuals across continuum between schizophrenia and bipolar disorder. However, there is a significant heterogeneity of neuropsychological and social cognitive abilities in schizophrenia, schizoaffective disorder and bipolar disorder. In recent years, several studies have investigated cognitive subgroups in schizophrenia-bipolar disorder continuum using data-driven methods and found that bipolar disorder includes several subgroups including a severely impaired and a neurocognitively intact clusters. However, neurodevelopmental and clinical characteristics of cognitive subgroups are not clear.Methods147 clinically stable patients with schizophrenia, schizoaffective or bipolar disorder were assessed using clinical rating scales for current psychotic and affective symptoms, schizobipolar scale, and a comprehensive neuropsychological battery including measures of ToM (Hinting and Reading the mind from the Eyes (RMET) task)). Developmental history and premorbid academic functioning were also evaluated. The study also included 37 healthy controls. Neurocognitive subgroups were investigated using latent class analysis (LCA). The optimal number of clusters were determined based on Bayesian information criterion. Logistic regression analysis were conducted to investigate the predictors of the membership to globally impaired subgroup.ResultsLCA revealed two neurocognitive clusters including generally impaired (n=89, 60.5 %) and near-normal cognitive functioning (n=58, 39.5 %) subgroups. The generally impaired subgroup significantly underperformed both groups in memory, executive functions, processing speed, attention and both aspects of ToM. The near-normal cognitive functioning subgroup did not significantly underperformed healthy controls except RMET (p=0.01). The generally impaired subgroup had a history of increased number of developmental abnormalities (p=0.03) and more severe disorganised speech (p=0.02) compared to the near-normal cognitive functioning group. The near-normal subgroup had a significantly higher percentage of individuals with a history of good academic performance in childhood than the globally impaired group (p=0.002). Compared to the near-normal subgroup, the globally impaired subgroup was significantly older (p<0.001) and had mothers who were less educated (p=0.02). While relatively higher percentage of patients with bipolar disorder than schizophrenia were members of the near-normal functioning subgroup (and opposite for the generally impaired subgroup), the between-group difference was not significant. Logistic regression analysis suggested that both the number of neurodevelopmental abnormalities (p=0.02) and disorganised speech (p=0.05) were significant predictors of being included in the globally cognitive impaired subgroup (Log likelihood=144. 4, R2=0.23, p=0.003, percentage correctly identified as globally impaired 81.1 %).DiscussionHistory of developmental abnormalities and persistent disorganisation rather than diagnosis are the significant predictors of the subgroup of individuals with global cognitive impairment in schizophrenia-bipolar disorder continuum. Studies investigating neurobiological and genetic underpinnings of the relationship between cognitive impairment, neurodevelopmental abnormalities and persistent disorganised speech might be important to develop a more valid classification of disorders presenting with psychotic and mood symptoms.

M226. ECOLOGICAL MOMENTARY ASSESSMENT OF REAL-WORLD FUNCTIONING IN SCHIZOPHRENIA: MODERATING EFFECTS OF COGNITIVE AND FUNCTIONAL ABILITY STATUS

BackgroundNeurocognitive and functional heterogeneity is common in schizophrenia (SZ), and functioning is notoriously difficult to measure. Ecological Momentary Assessment (EMA) may help overcome the retrospective recall and subjective biases associated with standard self-report measures; however, how EMA-measured real-world functioning indicators align with other neurocognitive and functional capacity indicators is not well established. The current study aimed to characterize individuals with schizophrenia-spectrum disorders based upon their objective global neurocognitive functioning and functional capacity, and examine differences in EMA-measured functioning.MethodsThe study included 100 outpatient, English-speaking adults with SZ (n=82) or schizoaffective disorder (n=18). All participants completed EMA surveys administered at stratified random intervals 7 times per day for 7 days to assess self-rated proficiency in performing activities within home-care, self-care, leisure, work/school, and treatment engagement dimensions, as well as need for assistance/prompting to complete the tasks. Moreover, participants completed an in-lab comprehensive neuropsychological assessment battery (MATRICS Consensus Cognitive Battery) and a performance-based measure of functional capacity (UCSD Performance-Based Skills Assessment-Brief [UPSA-B]). Latent profile analyses (LPA) were used to derive categorical latent variables that represent profiles of individuals who have similar global neurocognitive functioning and UPSA-B performance. The optimal number of profiles for the sample was determined by evaluating models using the Akaike information criteria (AIC; Akaike, 1974), sample size-adjusted Bayesian information criteria (sBIC; Schwarz, 1978), and the Lo–Mendell–Rubin Adjusted Likelihood Ratio Test (LMRT; Lo, Mendell, & Rubin, 2001). Independent samples t-tests were used to examine group differences between the identified latent profile groups on EMA-reported outcomes.ResultsLPA identified a 2-profile solution with the best fit; participants in profile 1 (n=43) demonstrated mild-to-moderate global cognitive impairment and lower UPSA-B scores (Low functioning; LF), whereas participants in profile 2 (n=57) demonstrated average cognitive functioning and higher UPSA-B performance (High functioning; HF). The groups did not significantly differ on number of EMA surveys answered (p=.12). Compared to the HF group, the LF group reported poorer proficiency in overall reported activities (p=.001), which was driven by lower reported proficiency in home-care, self-care, and leisure activities (ps<.003). Compared to the HF group, the LF group also indicated requiring more assistance and/or prompting in performing productive activities (p=.02), specifically within the life domains of home-care, self-care, and in-home leisure activities (ps<.03).DiscussionCompared to HF participants, LF participants rated their performance in activities within various life dimensions as less proficient and reported receiving greater assistance and/or prompting to do the activities. Future research should investigate the utility of the EMA paradigm to provide psychosocial interventions that appreciate the role of cognition and functional capacity in daily functioning.

M115. COGNITIVE FUNCTION IN BIPOLAR AND SCHIZOPHRENIA OFFSPRING: FINDINGS ACROSS THE NEURODEVELOPMENTAL CONTINUUM

BackgroundNeurocognitive impairment is considered to lie on a continuum of severity across schizophrenia (SZ) and bipolar disorder (BP), possibly reflecting a continuum of neurodevelopmental load. Due to the known heterogeneity, performance patterns across both disorders have been examined using clustering approaches, which previously identified subgroups with different levels of impairment, from none to widespread and severe. We, for the first time, used this approach to examine cognitive function in children and youth at familial risk of developing SZ and BP, in order to investigate cognitive profiles earlier on in the neurodevelopmental pathway.Methods220 participants, 49 offspring of individuals with schizophrenia (SZO), 90 offspring of individuals with bipolar disorder (BPO) and 81 healthy controls (HC), underwent a comprehensive cognitive assessment. Measures of attention, verbal memory, visual memory, executive function, working memory, and processing speed were used to group high-risk offspring. The k-means clustering with elbow method was used to determine the optimal number of clusters. High-risk offspring were then each assigned to a specific cluster. Cognitive performance within each of the clusters was compared to that of HC in order to describe the distribution of impairments across different cognitive domains and their severity. Between–cluster comparisons were then performed in terms of clinical and functioning variables.ResultsThree cognitive subgroups were identified for high-risk offspring: a global impairment group (19.5%) with severe impairments across most cognitive domains, a selective impairment group (46%) with moderate deficits across specific domains, and a cognitively intact group (34.5%) with performance comparable to that of healthy controls. Both SZO and BPO were represented in each of the three clusters. However a larger proportion of the SZO (30.6%) than of the BPO (13.3%) were characterised by widespread cognitive dysfunction, whereas BPO (41.1%) were more frequently cognitively spared relative to SZO (22.4%). Individuals in the global cognitive impairment group displayed significantly poorer clinical and functioning measures relative to the other two clusters.DiscussionThree cognitive subgroups were identified in BP and SZ offspring, a global impairment group, a selective impairment group and a cognitively intact group. The clustering pattern identified overlaps with that previously observed after illness onset.Findings are in line with the known heterogeneity in cognitive impairment across SZ and BP and can contribute to elucidate the timeframe of its emergence.Using cognitive function as a proxy measure of neurodevelopmental load, the findings point to a gradient in individuals at genetic risk of SZ and BP. They have therefore important implications for the understanding of potentially different neurodevelopmental trajectories within SZ and BP, hence for patient stratification in research and clinical practice.

Cognitive decline profiles differ in Parkinson disease dementia and dementia with Lewy bodies.

To examine whether domain-specific patterns of cognitive impairment and trajectories of decline differed in patients with clinically diagnosed Parkinson disease dementia (PDD) (N = 29) and autopsy-confirmed dementia with Lewy bodies (DLB) (N = 58) or Alzheimer disease (AD) (N = 174) and to determine the impact of pooling patients with PDD and DLB in clinical trials targeting cognition. Patients were matched on demographics and level of global cognitive impairment. Patterns of cross-sectional performance and longitudinal decline were examined in 4 cognitive domains: Visuospatial, Memory, Executive, and Language. Power analyses were performed to determine the numbers of participants needed to adequately power a hypothetical clinical trial to slow cognitive decline in pure PDD, pure DLB, or a mixed PDD/DLB group. Both DLB and PDD were more impaired and declined more rapidly than AD in the Visuospatial domain. Patients with PDD exhibited the most impairment and fastest decline in Executive, although patients with DLB also declined faster than AD. Memory was more impaired in AD than DLB and in both compared with PDD; however, all 3 groups declined at comparable rates. In contrast, PDD declined at a slower rate on Language measures than DLB or AD. Power analyses suggest that Visuospatial and Executive outcome measures would be most sensitive in PDD, but Memory and Language in DLB. DLB and PDD differ from each other, and from AD, in a cognitive domain-specific manner. As such, different outcome measures may be most sensitive to detecting changes in DLB vs PDD, suggesting that the 2 should be analyzed separately in clinical trials.

Diabetes, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (HCHS/SOL).

Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos. The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes. Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models. Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.

Abstract P268: Greater Cognitive Impairment Among Older Adults With Type 1 Diabetes as Compared to Non-diabetic Controls: Results From the Study of Longevity in Diabetes (SOLID)

Introduction: Studies have shown poorer cognitive function in children and adolescents with type 1 diabetes (T1D) as compared to non-diabetic peers. However, little is known about cognitive function in older adults with T1D. Hypothesis: We hypothesized that older adults with T1D and type 2 diabetes (T2D) would have greater cognitive impairment than age, sex, race/ethnicity, and education-matched controls without diabetes. Methods: We compared baseline cognitive impairment among older adults (aged ≥60) from the Study of Longevity in Diabetes (SOLID) with T1D (n=771), T2D (=234) and no diabetes (n=253). Cognitive tests assessed three cognitive domains identified via factor analysis (language, executive function, episodic memory). All cognitive test scores were standardized and cognitive impairment was defined as 1.5 SD below the mean. In logistic regression models adjusted for age, sex, education, and race/ethnicity, we examined the association between diabetes status (T1D, T2D or no diabetes) and cognition on each cognitive domain and on global cognition (average of scores on the 3 domains). Results: In adjusted regression models, compared to older adults without diabetes, those with T1D were more likely to have impaired cognitive function on the language (OR=2.13, 95% CI: 1.08, 4.17) and executive function domains (OR=2.66, 95% CI: 1.36, 5.22). No significant differences in global cognitive impairment or impairment on the episodic memory domain were observed for T1D and no significant differences on any domain were observed for T2D. Conclusions: Our findings suggest that older adults with T1D have greater cognitive impairment than their peers without diabetes; findings were specific to the language and executive function domains, with episodic memory being unaffected. No increase in cognitive impairment was observed for older adults with T2D. Additional research is needed to understand the causes and potentially modifiable factors associated with impaired cognition among older adults with T1D.

Severe Hypoglycemia and Cognitive Function in Older Adults With Type 1 Diabetes: The Study of Longevity in Diabetes (SOLID).

In children with type 1 diabetes (T1D), severe hypoglycemia (SH) is associated with poorer cognition, but the association of SH with cognitive function in late life is unknown. Given the increasing life expectancy in people with T1D, understanding the role of SH in brain health is crucial. We examined the association between SH and cognitive function in 718 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Subjects self-reported recent SH (previous 12 months) and lifetime history of SH resulting in inpatient/emergency department utilization. Global and domain-specific cognition (language, executive function, episodic memory, and simple attention) were assessed. The associations of SH with cognitive function and impaired cognition were evaluated via linear and logistic regression models, respectively. Thirty-two percent of participants (mean age 67.2 years) reported recent SH and 50% reported lifetime SH. Compared with those with no SH, subjects with a recent SH history had significantly lower global cognition scores. Domain-specific analyses revealed significantly lower scores on language, executive function, and episodic memory with recent SH exposure and significantly lower executive function with lifetime SH exposure. Recent SH was associated with impaired global cognition (odds ratio [OR] 3.22, 95% CI 1.30, 7.94) and cognitive impairment on the language domain (OR 3.15, 95% CI 1.19, 8.29). Among older adults with T1D, recent SH and lifetime SH were associated with worse cognition. Recent SH was associated with impaired global cognition. These findings suggest a deleterious role of SH on the brain health of older patients with T1D and highlight the importance of SH prevention.

Individual and neighbourhood socioeconomic inequalities in cognitive impairment: cross-sectional findings from the French CONSTANCES cohort

ObjectivesDespite the recent awareness of the environment impact on brain ageing, the influence of the neighbourhood socioeconomic status on cognitive impairment remains unclear. Here, we investigated the effects of individual...

A comprehensive examination of the memory profile of youth with Down syndrome in comparison to typically developing peers

ABSTRACT Down syndrome (DS) is associated with significant memory deficits beyond overall global cognitive impairment. Although a number of studies have examined memory abilities in adults and teens with DS, very few studies have examined memory abilities in children with DS. Additionally, research has yet to examine prospective memory (i.e., remembering to carry out an action in the future) in youth with DS. Consequently, the current study aimed to comprehensively examine the memory profile, including learning, immediate recall, delayed recall and prospective memory, of youth with DS (n = 22, age M = 11.43) in comparison to typically developing, mental-age (MA) matched children (n = 20, age M = 5.04) Consistent with past research, the results indicated that youth with DS performed significantly below MA-expectations on tasks of immediate verbal recall, learning across trials, and prospective memory, and there was a trend toward youth with DS performing below MA-expectations on delayed recall tasks. However, youth with DS did not differ significantly from MA-matched peers on immediate visual recall, rate of learning across trials, or proportion of items recalled on verbal and visual memory tasks following a delay (i.e., proportion relative to their own recall performance prior to the delay). These results highlight the relative strengths and challenges experienced by youth with DS on different learning and memory tasks. The implications of these findings for educators and caregivers are discussed.

Association between occupational solvent exposure and cognitive performance in the French CONSTANCES study

ObjectiveThe objective of this study was to evaluate the association between occupational exposure to solvents and cognitive performance in middle-aged and early-ageing participants, taking into account the working environment.MethodsIn the...

Word retrieval across the biomarker-confirmed Alzheimer's disease syndromic spectrum

Alzheimer's disease (AD) is now conceptualized as a biological entity defined by amyloid and tau deposition and neurodegeneration, with heterogeneous clinical presentations. With the aid of in vivo biomarkers, clinicians are better poised to examine clinical syndromic variability arising from a common pathology. Word retrieval deficits, measured using verbal fluency and confrontation naming tests, are hallmark features of the early clinical stages of the amnestic presentations of AD, specifically in category fluency and naming with relatively spared letter fluency. As yet, there is no consensus regarding performance on these tests in atypical clinical phenotypes of AD, including posterior cortical atrophy (PCA) and logopenic primary progressive aphasia (lvPPA), in individuals who are amyloid-positive (Aβ+) but present with different clinical profiles and patterns of neurodegeneration compared to amnestic AD. The goal of the current study is to determine how Aβ+ individuals across the syndromic spectrum of AD perform on three different word retrieval tasks. A secondary goal is to determine the neuroanatomical substrates underlying word retrieval performance in these Aβ+ individuals. Thirty-two Aβ+ participants with the amnestic presentation, 16 with Aβ+ PCA, 22 with Aβ+ lvPPA, and 99 amyloid-negative (Aβ-) control participants were evaluated with verbal fluency and visual confrontation naming tests as well as high-resolution MRI. The Aβ+ patient groups were rated at very mild or mild levels of severity (CDR 0.5 or 1) and had comparable levels of global cognitive impairment (average MMSE = 23.7 ± 3.9). Behaviorally, we found that the word retrieval profile of PCA patients is comparable to that of amnestic patients, characterized by intact letter fluency but impaired category fluency and visual confrontation naming, while lvPPA patients demonstrated impairment across all tests of word retrieval. Across all AD variants, we observed that letter fluency was associated with cortical thickness in prefrontal, central precuneus, lateral parietal and temporal cortex, while category fluency and naming were associated with cortical thickness in left middle frontal gyrus, posterior middle temporal gyrus, and lateral parietal cortex. Visual confrontation naming was uniquely associated with atrophy in inferior temporal and visual association cortex. We conclude that a better understanding of the word retrieval profiles and underlying neurodegeneration across the AD syndromic spectrum will help improve interpretation of neuropsychological profiles with regard to the localization of neurodegeneration, particularly in the atypical AD variants.

The effect of ApoE ε 4 on clinical and structural MRI markers in prodromal Alzheimer's disease.

Apolipoprotein E (ApoE) ε 4 has been identified as the strongest genetic risk factor for Alzheimer's disease (AD). However, the importance of ApoE ε 4 on clinical and biological heterogeneity of AD is still to be determined, particularly at the prodromal stage. Here, we evaluate the association of ApoE ε 4 with clinical cognition and neuroimaging regions in mild cognitive impairment (MCI) participants based on the AT (N) system, which is increasingly essential for developing a precise assessment of AD. We stratified 178 A+T+MCI participants (prodromal AD) into ApoE ε 4 (+) and ApoE ε 4 (-) according to ApoE genotype from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We determined Aβ-positivity (A+) by the standardized uptake values ratios (SUVR) means of florbetapir-PET-AV45 (the cut-off value of 1.1) and fibrillar tau-positivity (T+) by cerebrospinal fluid (CSF) phosphorylated-tau at threonine 181 position (p-Tau) (cut-off value of 23 pg/mL). We evaluated the effect of ApoE ε 4 status on cognitive conditions and brain atrophy from structural magnetic resonance imaging (MRI) scans. A multivariate analysis of variance was used to compare the differences of cognitive scores and brain atrophy from structural MRI regions of interest (ROIs) between both groups. Furthermore, we performed a linear regression model to assess the correlation between signature ROIs of structural MRI and cognitive scores in the prodromal AD participants. ApoE ε 4 (+) prodromal AD participants had lower levels of CSF Aβ 1-42, higher levels of t-Tau, more memory and global cognitive impairment, and faster decline of global cognition, compared to ApoE ε 4 (-) prodromal AD. ApoE ε 4 (+) prodromal AD participants had a thinner cortical thickness of bilateral entorhinal, smaller subcortical volume of the left amygdala, bilateral hippocampus, and left ventral diencephalon (DC) relative to ApoE ε 4 (-) prodromal AD. Furthermore, the cortical thickness average of bilateral entorhinal was highly correlated with memory and global cognition. ApoE ε 4 status in prodromal AD participants has an important effect on clinical cognitive domains. After ascertaining the ApoE ε 4 status, specific MRI regions can be correlated to the cognitive domain and will be helpful for precise assessment in prodromal AD.

Psychotropic Polypharmacy in Adults 55 Years or Older: A Risk for Impaired Global Cognition, Executive Function, and Mobility.

ObjectivesWith their broad spectrum of action, psychotropic drugs are among the most common medications prescribed to the elderly. Consequently, the number of older adults taking multiple psychotropic drugs has more than doubled over the last decade. To improve knowledge about the deleterious effects of psychotropic polypharmacy, we investigated whether there is a threshold number of psychotropic molecules that could lead to impairment of global cognition, executive function, or mobility. Furthermore, relationships between the number of psychotropic molecules and cognitive and mobility impairment were examined.DesignCross-sectional studySettingUniversity Hospital of Caen (France) and advertisements in medical officesParticipantsCommunity-dwelling older adults 55 years and older (n = 177; 69.8 ± 9.3 years; 81% women)MeasurementsNumber of psychotropic molecules taken daily, global cognition assessed with the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), processing speed with the Trail Making Test (TMT) A, executive function with the TMT B and TMT B-A, and mobility with the Time Up and Go (TUG). The threshold numbers of psychotropic molecules were determined by ROC curves analysis. Based on these threshold values, multinomial logistic regression adjusting for covariates was then performed.ResultsLogistic regressions showed that the threshold of two daily psychotropic molecules, identified by the ROC curves analysis, increases the risk of impaired executive function (p = .05 and.005 for the TMT B and TMT B-A, respectively), global cognition (p = .006 and.001 for the MMSE and MoCA, respectively), and mobility (p = .005 for the TUG), independent of confounding factors, including comorbidities. Furthermore, psychotropic polypharmacy would affect mobility through executive functions.ConclusionImpairment of global cognition, executive function, and mobility when as few as two psychotropic molecules are consumed in relatively healthy young older adults should alert physicians when prescribing combinations of psychotropic medications.

Cognitive validation of cross-diagnostic cognitive subgroups on the schizophrenia-bipolar spectrum

BackgroundCognitive heterogeneity in schizophrenia spectrum disorders (SSD) and bipolar disorder (BD) has been explored using clustering analyses. However, the resulting subgroups have not been cognitively validated beyond measures used as clustering variables themselves. We compared the emergent cross-diagnostic subgroups of SSD and BD patients on measures used to classify them, and also across a range of alternative cognitive measures assessing some of the same constructs. MethodDomain scores from the Matrics Consensus Cognitive Battery were used in a cross-diagnostic clustering analysis of 86 patients with SSD (n = 45) and BD (n = 41). The emergent subgroups were then compared to each other and healthy controls (n = 76) on these and alternative measures of these domains, as well as on premorbid IQ, global cognition and a proxy of cognitive decline. ResultsA three-cluster solution was most appropriate, with subgroups labelled as Globally Impaired, Selectively Impaired, and Superior/Near-Normal relative to controls. With the exception of processing speed performance, the subgroups were generally differentiated on the cognitive domain scores used as clustering variables. Differences in cognitive performance among these subgroups were not always statistically significant when compared on the alternative cognitive measures. There was evidence of global cognitive impairment and putative cognitive decline in the two cognitively impaired subgroups. LimitationsFor clustering analysis, sample size was relatively small. ConclusionsThe overall pattern of findings tentatively suggest that emergent cross-diagnostic cognitive subgroups are not artefacts of the measures used to define them, but may represent the outcome of different cognitive trajectories.

Everyday Function in Alzheimer's and Parkinson's Patients with Mild Cognitive Impairment.

Instrumental activities of daily living (IADL) impairment can begin in mild cognitive impairment (MCI), and is the core criteria for diagnosing dementia in both Alzheimer's (AD) and Parkinson's (PD) diseases. The Functional Activities Questionnaire (FAQ) has high discriminative power for dementia and MCI in older age populations, but is influenced by demographic factors. It is currently unclear whether the FAQ is suitable for assessing cognitive-associated IADL in non-demented PD patients, as motor disorders may affect ratings. To compare IADL profiles in MCI patients with PD (PD-MCI) and AD (AD-MCI) and to verify the discriminative ability of the FAQ for MCI in patients with (PD-MCI) and without (AD-MCI) additional motor impairment. Data of 42 patients each of PD-MCI, AD-MCI, PD cognitively normal (PD-CN), and healthy controls (HC), matched according to age, gender, education, and global cognitive impairment were analyzed. ANCOVA and binary regressions were used to examine the relationship between the FAQ scores and groups. FAQ cut-offs for PD-MCI (versus PD-NC) and AD-MCI (versus HC) were separately identified using receiver operating characteristic analyses. FAQ total score did not differentiate between MCI groups. PD-MCI subjects had greater difficulties with tax records and traveling while AD-MCI individuals were more impaired in managing finances and remembering appointments. Classification accuracy of the FAQ was good for diagnosing AD-MCI (69%, cut-off ≥1) compared to HC, and sufficient for differentiating PD-MCI (38.1%, cut-off ≥3) from PD-CN. The FAQ task profiles and classification accuracy differed between MCI related to PD and AD.

Association of Androgens and Gonadotropins with Amnestic Mild Cognitive Impairment and Probable Alzheimer's Disease in Chinese Elderly Men.

Age-related hormone changes play important roles in cognitive decline in older men, and apolipoprotein E ɛ4 (APOEɛ4) is a risk factor for Alzheimer's disease (AD). This study aimed to investigate the interactive role of androgen decline and APOEɛ4 genotype in the pathogenesis of amnestic mild cognitive impairment (aMCI) and AD. In total, 576 elderly men over 65 years old from communities in Shijiazhuang were enrolled in this study, including 243 with normal cognition (NC), 271 with aMCI, and 62 with probable AD. Cognitive function was evaluated with a battery of neuropsychological tests. The serum levels of androgen and gonadotropin were detected by ELISA and chemiluminescence immunoassay. The levels of free testosterone (FT) and dihydrotestosterone (DHT) were lower in the aMCI group (p < 0.05), and even lower in the AD group (p < 0.001), but the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH)were higher in AD group (p < 0.01), comparing with that in NC or aMCI group. The interaction of lower FT or DHT levels with APOEɛ4 had a risk role in global cognitive impairment (p < 0.05). The area under the curve (AUC) of the ROC curve for predicting aMCI by serum FT levels was 0.745. These results indicated that the interaction of androgen decline and APOEɛ4 genotype play a role in aMCI and AD. Serum FT levels have a predictive value for aMCI and might be a potential biomarker for prodromal AD.

Neurocognitive heterogeneity in patients with bipolar disorder and their unaffected relatives: associations with emotional cognition.

Recent evidence suggests that neurocognitive impairments in remitted patients with bipolar disorder (BD) are heterogeneous. Our study aims to replicate recent findings of neurocognitive subgroups, and further explore whether these are related to impairments in affective cognition, in a large sample of remitted patients recently diagnosed with BD and their unaffected relatives compared to healthy controls (HCs). Hierarchal cluster analysis was conducted using neurocognitive data from remitted patients with BD (n = 158). Relatives of patients with BD (n = 52) were categorised into groups consistent with their affected relative's cluster assignment. The neurocognitive clusters of patients with BD and relatives, respectively, were compared with HCs (n = 110) in neurocognition and affective cognition (i.e. emotion processing and regulation). Three discrete neurocognitive clusters were identified in patients with BD: a globally impaired (23.4%), a selectively impaired (31.0%) and a cognitively intact cluster (45.6%). The neurocognitive subgroups differed in affective cognition, with patients categorised as globally impaired exhibited most impairments in facial expression recognition and emotion regulation in social scenarios. First-degree relatives of cognitively impaired patients displayed impaired facial expression recognition but no impairments in non-emotional cognition. In a clinical sample of remitted patients recently diagnosed with BD 54.4% had either global or selective cognitive impairment, replicating results of previous studies in patients with longer illness duration. The results suggest that patterns of neurocognition are associated with differential impairments in affective cognition. Aberrant affective cognition in relatives of patients categorised as neurocognitively impaired indicates an inherited risk for BD.

Longitudinal associations between diurnal cortisol variation and later-life cognitive impairment.

ObjectiveTo determine whether hypothalamus-pituitary-adrenal axis (HPAA) dysfunction is prospectively associated with global cognitive impairment in later life.MethodsThis cross-cohort study integrates 2 large longitudinal datasets, Whitehall II and the National Survey for Health and Development (NSHD), on data collected in the Whitehall II study between 2002–2004, 2007–2009, and 2012–2013; and for NSHD between 2006–2010 and in 2015. Serial salivary cortisol samples were collected multiple times within a 24-hour period at mean ages 61.2 and 65.9 years in Whitehall II and at age 60–64 years from NSHD participants. Cortisol profile is defined using cortisol awakening response and am:pm ratio. Cognitive function was measured using the Mini-Mental State Examination in Whitehall II and Addenbrooke’s Cognitive Examination, third version, in NSHD, harmonized into a 30-point score. Models were adjusted for age, sex, diagnoses of hypertension and diabetes, body mass index (BMI), educational attainment, and interval between HPAA and cognitive assessments.ResultsIn fully adjusted models, increased am:pm cortisol ratio was prospectively associated with better later-life cognitive function years later (0.02 fewer errors per SD increase in am:pm cortisol ratio, p < 0.01) and verbal fluency (0.03 SD increase in verbal fluency per SD increase in am:pm ratio, p < 0.01). Increasing age, lower educational attainment, diagnosis of hypertension, diagnosis of diabetes, and increased BMI were associated with worse cognitive function and poorer verbal fluency. There were no associations between depression and later-life cognition or reverse associations between cognition and later-life cortisol profiles.ConclusionsLoss of diurnal HPAA variation is evident in individuals subsequently experiencing more cognitive impairment. It may serve as an early preclinical marker of cognitive decline.