Locus coeruleus integrity and left frontoparietal connectivity provide resilience against attentional decline in preclinical alzheimer's disease.

BACKGROUND: Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (Aß)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer's disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology. METHODS: 142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(Aß)-PET, and up to 5 years of cognitive follow-ups were included (mean age = 74.5 ± 9.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates. RESULTS: At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB > 10.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (> 46 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity. CONCLUSIONS: Our findings demonstrate that the LC can provide resilience against Aß-related attention decline. However, when Aß accumulates and the LC's resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against Aß-related cognitive decline.

Neuropsychological Profiles of Deployment-Related Mild Traumatic Brain Injury: A LIMBIC-CENC Study.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is a concern for US service members and veterans (SMV), leading to heterogeneous psychological and cognitive outcomes. We sought to identify neuropsychological profiles of mild TBI (mTBI) and posttraumatic stress disorder (PTSD) among the largest SMV sample to date. METHODS: We analyzed cross-sectional baseline data from SMV with prior combat deployments enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Latent profile analysis identified symptom profiles using 35 indicators, including physical symptoms, depression, quality of life, sleep quality, postconcussive symptoms, and cognitive performance. It is important to note that the profiles were determined independently of mTBI and probable PTSD status. After profile identification, we examined associations between demographic variables, mTBI characteristics, and PTSD symptoms with symptom profile membership. RESULTS: The analytic sample included 1,659 SMV (mean age 41.1 ± 10.0 years; 87% male); among them 29% (n = 480) had a history of non-deployment-related mTBI only, 14% (n = 239) had deployment-related mTBI only, 36% (n = 602) had both non-deployment and deployment-related mTBI, and 30% (n = 497) met criteria for probable PTSD. A 6-profile model had the best fit, with separation on all indicators (p < 0.001). The model revealed distinct neuropsychological profiles, representing a combination of 3 self-reported functioning patterns: high (HS), moderate (MS), and low (LS), and 2 cognitive performance patterns: high (HC) and low (LC). The profiles were (1) HS/HC: n=301, 18.1%; (2) HS/LC: n=294, 17.7%; (3) MS/HC: n=359, 21.6%; (4) MS/LC: n=316, 19.0%; (5) LS/HC: n=228, 13.7%; and (6) LS/LC: n=161, 9.7%. SMV with deployment-related mTBI tended to be grouped into lower functioning profiles and were more likely to meet criteria for probable PTSD. Conversely, SMV with no mTBI exposure or non-deployment-related mTBI were clustered in higher functioning profiles and had a lower likelihood of meeting criteria for probable PTSD. DISCUSSION: Findings suggest varied symptom and functional profiles in SMV, influenced by injury context and probable PTSD comorbidity. Despite diagnostic challenges, comprehensive assessment of functioning and cognition can detect subtle differences related to mTBI and PTSD, revealing distinct neuropsychological profiles. Prioritizing early treatment based on these profiles may improve prognostication and support efficient recovery.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. METHODS: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). RESULTS: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. DISCUSSION: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. METHODS: People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. RESULTS: Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. DISCUSSION: Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

Memory changes in patients with hippocampal sclerosis submitted to surgery to treat mesial temporal lobe epilepsy.

PURPOSE: This study was performed with the purpose of analysing the relationship between epileptological and surgical variables and post-operative memory performance, following surgery for refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). METHODS: Logical memory (LM) and visual memory (VM) scores for immediate and late follow-up of 201 patients operated for MTLE/HS were reviewed. Scores were standardized with a control group of 54 healthy individuals matched for age and education. The Reliable Change Index (RCI) was calculated to verify individual memory changes for late LM and VM scores. A multiple linear regression analysis was carried out with the RCI, using LM and VM scores as well as the clinical variables. RESULTS: A total of 112 (56%) patients had right HS. The RCI of the right HS group demonstrated that 6 (7%) patients showed improvement while 5 (6%) patients showed decreased scores in late LM; for late VM, 7 (8%) patients presented improvement, and 2 (3%) patients showed poorer scores. RCI of the left HS group showed that 3 (3%) individuals showed improved scores, while scores of 5 (4%) patients worsened for late LM; for late VM, 3 (3%) patients presented higher scores and 6 (5%) showed lower scores. Left HS and advanced age at onset of the first epileptic seizure were predictors of late LM loss (p<.05). CONCLUSION: Left MTLE/HS and seizure onset at advanced ages were predictive factors for the worsening of late LM. We observed poorer baseline LM function in the left HS group and improvement of LM in some patients who had resection of the right MTL. Patients in the right HS group showed a higher percentage of reliable post-operative improvement for both VM and LM scores.

Swallowing performance of elderly people and sociodemographic, cognitive and language factors. / Desempenho de deglutição de idosos e seus fatores sociodemográficos, cognitivos e de linguagem.

PURPOSE: To analyze the correlation between swallowing, language and cognition performance and describe the sociodemographic data of elderly people without previous neurological disorders. METHODS: Analytical cross-sectional study, with non-probabilistic sample for convenience and data collection by telecall. The aspiration screening test (Yale Swallow Protocol) was used to identify and exclude elderly people at risk of aspiration. Then, sociodemographic data were collected, and instruments were applied: activity of daily living (IADLs), risk of dysphagia (EAT-10), cognitive screening (Mini Mental State Examination - MMSE) and language (Montreal-Toulouse Language Battery - MTL-Brazil). RESULTS: The sample consisted of 32 elderly people from the Federal District, with a mean age of 69.00±7.73 years and schooling of 10.00±5.60 years. The scores on the EAT-10, MMSE and MTL Battery instruments were altered in four, 22 and 26 elderly, respectively, indicating, in this case, risk of dysphagia, suggestion of cognitive alteration and language alteration. Regarding food, of the total sample, 13 seniors (40%) complained of needing modified food, as well as 10 of these also obtained MMSE scores suggestive of cognitive alteration. When comparing the groups with and without complaints and/or risk of dysphagia, there was no statistically significant difference in relation to sociodemographic, cognitive and language variables. Binary logistic regression models also showed no statistically significant results. CONCLUSION: The present study, when correlating the swallowing, language and cognition findings, did not obtain statistically significant results. It was observed that the elderly with swallowing complaints also showed results suggestive of cognitive and language changes in the tests performed, but there was no statistically significant difference in relation to the elderly without complaints or swallowing changes.

OBJETIVO: Analisar a correlação entre o desempenho de deglutição, linguagem e cognição e descrever os dados sociodemográficos de idosos sem alterações neurológicas prévias. MÉTODO: Estudo transversal analítico, com amostra não-probabilística por conveniência e coleta de dados por telechamada. Foi aplicado o teste de triagem de broncoaspiração (Yale Swallow Protocol) para identificação e exclusão dos idosos com risco de broncoaspiração. Em seguida, realizou-se coleta de dados sociodemográficos e aplicação dos instrumentos de: atividade de vida diária (AIVDs), risco de disfagia (EAT-10), rastreio cognitivo (Mini Exame do Estado Mental ­ MEEM) e linguagem (Bateria Montreal-Toulouse de Linguagem ­ MTL-Brasil). RESULTADOS: A amostra foi composta por 32 idosos do Distrito Federal, com média de idade de 69,00±7,73 anos e de escolaridade de 10,00±5,60 anos. Os escores nos instrumentos EAT-10, MEEM e Bateria MTL apresentaram-se alterados em quatro, 22 e 26 idosos, respectivamente, indicando, nesse caso, risco de disfagia, sugestão de alteração cognitiva e alteração da linguagem. Sobre a alimentação, do total da amostra, 13 idosos (40%) apresentaram queixa de necessidade de comida modificada, bem como 10 desses também obtiveram escore no MEEM sugestivo de alteração cognitiva. Ao comparar os grupos com e sem queixa e/ou risco de disfagia, não houve diferença estatisticamente significante em relação às variáveis sociodemográficas, cognitivas e de linguagem. Os modelos de regressão logística binária também evidenciaram resultados sem significância estatística. CONCLUSÃO: O presente estudo, ao correlacionar os achados de deglutição, linguagem e cognição, não obteve resultados estatisticamente significantes. Observou-se que os idosos com queixa de deglutição também apresentaram resultados sugestivos de alteração cognitiva e de linguagem nos testes realizados, mas não houve diferença estatisticamente significante em relação aos idosos sem queixa ou alteração de deglutição.

Unveiling the cognitive network organization through cognitive performance.

The evaluation of cognitive functions interactions has become increasingly implemented in the cognition exploration. In the present study, we propose to examine the organization of the cognitive network in healthy participants through the analysis of behavioral performances in several cognitive domains. Specifically, we aim to explore cognitive interactions profiles, in terms of cognitive network, and as a function of participants' handedness. To this end, we proposed several behavioral tasks evaluating language, memory, executive functions, and social cognition performances in 175 young healthy right-handed and left-handed participants and we analyzed cognitive scores, from a network perspective, using graph theory. Our results highlight the existence of intricate interactions between cognitive functions both within and beyond the same cognitive domain. Language functions are interrelated with executive functions and memory in healthy cognitive functioning and assume a central role in the cognitive network. Interestingly, for similar high performance, our findings unveiled differential organizations within the cognitive network between right-handed and left-handed participants, with variations observed both at a global and nodal level. This original integrative network approach to the study of cognition provides new insights into cognitive interactions and modulations. It allows a more global understanding and consideration of cognitive functioning, from which complex behaviors emerge.

Chanwuyi Lifestyle Medicine Program Improves Memory and Executive Functions of Older Adults With Mild Cognitive Impairment.

The Chanwuyi Lifestyle Medicine Program (CLMP) was found to enhance the memory and executive functions of older adults with or without subjective memory complaints. The present study investigated whether similar beneficial effects can be extended to mild cognitive impairment (MCI). Twenty-four older adults with MCI were randomly assigned to receive the CLMP (the experimental group) or strategic memory training (SMT; the active control group) for 10 weeks. They were assessed by neuropsychological tests at baseline and post-intervention. Older adults showed similar visual and verbal memory improvements after receiving the CLMP and SMT. Yet, only those who received the CLMP showed distinct improvements in planning/organization, working memory, and attention in terms of accuracy, with greater cognitive gains associated with older age and lower levels of education and baseline cognitive functions. This study provides preliminary evidence for the effects of the CLMP on improving memory, attention, and executive functions in MCI.

Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer's disease, suspected-LATE and frontotemporal dementia.

BACKGROUND: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls. METHODS: Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy. RESULTS: We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients. CONCLUSIONS: The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.

The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.

The association between adherence to the EAT-Lancet diet and cognitive ageing.

BACKGROUND: The EAT-Lancet commission has proposed a dietary pattern that is both sustainable and healthy. However, the impact of this diet on cognition in older adults remains unexplored. Therefore, we examined the association between adherence to the EAT-Lancet diet and cognitive ageing. METHODS: We used data from a previous intervention study involving cognitively healthy community-dwelling adults aged ≥65 years. Adherence to the EAT-Lancet diet was calculated using a recently published index and a 190-item food frequency questionnaire. Global and domain-specific cognitive functioning were assessed at baseline and after 2 years using a neuropsychological test battery. Multivariate-adjusted linear regression was conducted to examine associations between EAT-Lancet diet adherence and cognitive functioning (n = 630) and 2-year change (n = 302). RESULTS: Greater adherence to the EAT-Lancet diet was associated with better global cognitive functioning (ß per SD = 3.7 points [95% CI]: 0.04 [0.00, 0.08]) and slower rate of decline (ß per SD [95% CI]: 0.05 [0.02, 0.08]). With respect to domain-specific functioning, beneficial associations were observed cross-sectionally for executive functioning (P < 0.01), and longitudinally for change in executive functioning (P < 0.01) and attention and working memory (P < 0.01). The degree of adherence to the EAT-Lancet was not associated with (changes in) information processing speed or episodic memory. CONCLUSION: We demonstrated that greater adherence to the EAT-Lancet diet is associated with better global cognitive functioning and slower cognitive decline among cognitively healthy older adults. Further research is needed to confirm these findings and assess the potential benefits of the EAT-Lancet diet for the ageing population in a broader context.

Handgrip strength is associated with cognitive function in older patients with stage 3-5 chronic kidney disease: results from the NHANES.

In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011-2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer's disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.

Memory capacity as the core mechanism of the development of space-time interferences in children.

This study investigated the development of spatiotemporal perceptual interactions in 5-to-7 years old children. Participants reproduced the temporal and spatial interval between sequentially presented visual stimuli. The time and spacing between stimuli were experimentally manipulated. In addition, cognitive capacities were assessed using neuropsychological tests. Results revealed that starting at 5 years old, children exhibited spatial biases in their time estimations and temporal biases in their spatial estimations, pointing at space-time interference. In line with developmental improvement of temporal and spatial abilities, these spatiotemporal biases decreased with age. Importantly, short-term memory capacity was a predictor of space-time interference pointing to shared cognitive mechanisms between time and space processing. Our results support the symmetrical hypothesis that proposes a common neurocognitive mechanism for processing time and space.

The hippocampus supports precise memory for public events regardless of their remoteness.

The necessity of the human hippocampus and surrounding medial temporal lobe structures to semantic memory remains contentious. Impaired semantic memory following hippocampal lesions could arise either due to partially intertwined episodic memories and/or retrograde/anterograde effects. In this study, we tested amnesic individuals with lesions in hippocampus and surrounding medial temporal lobe (n = 7) and age-matched controls (n = 14) on their ability to precisely recall the dates of famous public events that occurred either before (i.e., pre-lifetime) or after participants' birth date (lifetime). We show that deficits in dating precision are greatest for recent lifetime events, consistent with the notion that recent event memory may be particularly intertwined with episodic memory. At the same time, individuals with medial temporal lobe lesions showed more subtle impairments in their ability to date pre-birth and remote lifetime events precisely. Together, these findings suggest that the hippocampus and surrounding medial temporal lobe structures are important for representational precision of semantic memories regardless of their remoteness.

Clinical Characterization of Veterans With Alzheimer Disease by Disease Severity in the United States.

PURPOSE: We aimed to examine the clinical characteristics of US veterans who underwent neurocognitive test score-based assessments of Alzheimer disease (AD) stage in the Veterans Affairs Healthcare System (VAHS). METHODS: Test dates for specific stages of AD were referenced as index dates to study behavioral and psychological symptoms of dementia (BPSD) and other patient characteristics related to utilization/work-up and time to death. PATIENTS: We identified veterans with AD and neurocognitive evaluations using the VAHS Electronic Health Record (EHR). RESULTS: Anxiety and sleep disorders/disturbances were the most documented BPSDs across all AD severity stages. Magnetic resonance imaging, neurology and psychiatry consultations, and neuropsychiatric evaluations were slightly higher in veterans with mild AD than in those at later stages. The overall average time to death from the first AD severity record was 5 years for mild and 4 years for moderate/severe AD. CONCLUSION: We found differences in clinical symptoms, healthcare utilization, and survival among the mild, moderate, and severe stages of AD. These differences are limited by the low documentation of BPSDs among veterans with test score-based AD stages. These data support the hypothesis that our cohorts represent coherent subgroups of patients with AD based on disease severity.

A Transformer Approach for Cognitive Impairment Classification and Prediction.

INTRODUCTION: Early classification and prediction of Alzheimer disease (AD) and amnestic mild cognitive impairment (aMCI) with noninvasive approaches is a long-standing challenge. This challenge is further exacerbated by the sparsity of data needed for modeling. Deep learning methods offer a novel method to help address these challenging multiclass classification and prediction problems. METHODS: We analyzed 3 target feature-sets from the National Alzheimer Coordinating Center (NACC) dataset: (1) neuropsychological (cognitive) data; (2) patient health history data; and (3) the combination of both sets. We used a masked Transformer-encoder without further feature selection to classify the samples on cognitive status (no cognitive impairment, aMCI, AD)-dynamically ignoring unavailable features. We then fine-tuned the model to predict the participants' future diagnosis in 1 to 3 years. We analyzed the sensitivity of the model to input features via Feature Permutation Importance. RESULTS: We demonstrated (1) the masked Transformer-encoder was able to perform prediction with sparse input data; (2) high multiclass current cognitive status classification accuracy (87% control, 79% aMCI, 89% AD); (3) acceptable results for 1- to 3-year multiclass future cognitive status prediction (83% control, 77% aMCI, 91% AD). CONCLUSION: The flexibility of our methods in handling inconsistent data provides a new venue for the analysis of cognitive status data.

An algorithm for the early diagnosis and correct approach to dementia management: results of a multiprofessional team.

BACKGROUNG: The early identification of cognitive disorder is a primary scope, because it could reduce the rate of severe cognitive impairment and thus contribute to reduce healthcare costs in the next future. AIMS: The present paper aimed to build a virtuous diagnostic path of cognitive impairment, highlighting all the professionalism that can serve this purpose. METHODS: The Delphi method was used by the experts, who reviewed the information available during each meeting related to the following topics: early diagnosis of cognitive impairment, definition of Mild Cognitive Impairment, unmet needs in post-stroke patients, critical decision-making nodes in complex patients, risk factors, neuropsychological, imaging diagnosis, blood tests, the criteria for differential diagnosis and the possible treatments. RESULTS: The discussion panels analyzed and discussed the available evidences on these topics and the related items. At each meeting, the activities aimed at the creation of a diagnostic-welfare flow chart derived from the proposal of the board and the suggestions of the respondents. Subsequently, the conclusions of each panel were written, and the study group reviewed them until a global consensus was reached. Once this process was completed, the preparation of the final document was carried out. CONCLUSIONS: Eventually, we built an algorithm for the early diagnosis and treatment, the risk factors, with the possible differences among the different kinds of dementia.

Effectiveness of Early Multimodal Non-pharmacological Interventions in Cognitive Preservation in the Elderly.

INTRODUCTION: Multimodal non-pharmacological interventions (MNPI) have been determined as effective in delaying cognitive deterioration. The effectiveness of timing of such interventions in elderly is less discussed. We compared the different effectiveness of MNPI in cognitive preservation in elderly subjects with and without dementia. METHODS: We enrolled volunteer the elderly subjects. Subjects were classified as dementia group and non-dementia group by instrument of ascertainment of dementia 8. All were assigned to attend 3 hours of MNPI (physical fitness training, Chinese capillary, and Chinese drawings and paintings) twice a week over a 16-week period. Neuropsychiatric tests, including Mini-Mental State Examination (MMSE), Cognitive Assessment Screening Instrument (CASI), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI), were administered before and 1 year after MNPI. We demonstrated the changes of cognition and behavioral and psychological symptoms of dementia (BPSD) before and after MNPI. We compared the different effectiveness of cognition preservation between two groups. RESULTS: In total, there were 43 participants in our study, including 18 with non-dementia and 25 with dementia. The non-dementia group had a significantly higher proportion of cognitive preservation in remote memory (100.0% vs 68.0%, P = .007), orientation (94.4% vs 48.0%, P = .001), drawing (94.4% vs 64.0%, P = .021) and language (77.8% vs 48.0%, P = .049) than the dementia group. The highest proportion of preserved cognition after MNPI was remote memory (100%), followed by orientation (94.4%) and drawing (94.4%) in the non-dementia group. The highest proportion of preserved cognition after MNPI was attention (72%) followed by remote memory (68%), recent memory (64%) and drawing (64%) in the dementia group. Overall, their improved rate in behavioral and psychological symptoms was 55.6%. CONCLUSION: Our study concluded the benefits of early MNPI in cognition preservation in the elderly, especially in the field of remote memory, orientation, drawing and language.

Language impairment in sporadic and familial (type 8) amyotrophic lateral sclerosis: A comparative study.

INTRODUCTION/AIMS: Language is frequently affected in patients with sporadic amyotrophic lateral sclerosis (sALS), with reduced performance in naming, syntactic comprehension, grammatical expression, and orthographic processing. However, the language profile of patients with familial type 8 ALS (ALS8), linked to p.P56S VAPB mutation, remains unclear. We investigated language in patients with ALS8 by examining their auditory comprehension and verbal production. METHODS: We included three groups of participants: (1) patients with sALS (n = 20), (2) patients with familial ALS8 (n = 22), and (3) healthy controls (n = 21). The groups were matched for age, sex, and education level. All participants underwent a comprehensive language battery, including the Boston Diagnostic Aphasia Examination, the reduced Token test, letter fluency, categorical fluency (animals), word definition from the Cambridge Semantic Memory Research Battery, and a narrative discourse analysis. Participants also were evaluated using Addenbrooke's Cognitive Exam-Revised Version, the Hospital Anxiety and Depression Scale, and the ALS Functional Rating Scale-Revised. RESULTS: Compared to controls, sALS and ALS8 patients had impaired performance on oral (syntactic and phonological processing) comprehension and inappropriate discourse cohesion. sALS and ALS8 did not differ in any language measure. There was no correlation between language scores and functional and psychiatric scales. DISCUSSION: ALS8 patients exhibit language deficits that are independent of motor features. These findings are consistent with the current evidence suggesting that ALS8 has prominent non-motor features.

Development of Malaysian-MIND diet scores for prediction of mild cognitive impairment among older adults in Malaysia.

BACKGROUND: Mild Cognitive impairment (MCI) is a pre-demented state in the elderly populace. The Mediterranean & Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet has shown promise in reducing the risk of MCI and Alzheimer's disease in older people. Notably, the existing MIND diet is not adapted to the specific needs of older adults in Malaysia, considering distinct food cultures and availability. Consequently, this study aimed to develop the Malaysian version of the MIND diet (MY-MINDD) scores and investigate their association with MCI in the older adult populace of Malaysia. METHODS: A comprehensive pooled data analysis was conducted on combined data from 810 participants sourced from the longitudinal Long-Term Research Grant Scheme-Towards Useful Aging (LRGS-TUA) and Fundamental Research Grant Scheme (FRGS) studies. The MY-MINDD scores were developed by incorporating existing MIND diet food groups, their corresponding scoring mechanisms, and consideration of common Malaysian foods which are proven to be beneficial and detrimental to cognitive function. To substantiate the MY-MINDD scoring system, its association with MCI was evaluated using a series of validated neuropsychological test batteries. RESULTS: MY-MINDD consists of seven food groups promote brain health and four food groups exert negative cognitive outcomes. The study participants had an average age of 67.9 ± 4.7 years. The collective MY-MINDD score for all participants was 6.4 ± 0.1 (out of a maximum 11 points), revealing a lower score in individuals with MCI at 6.0 ± 1.7 compared to those without MCI at 6.6 ± 1.6 (p < 0.001). According to hierarchical multivariate binary logistic regression analysis, being in the highest tertile of MY-MINDD score was linked to reduced odds of MCI (odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.26-0.72, p < 0.001) in the fully adjusted model in comparison to the lowest tertile. CONCLUSION: The development of the MY-MINDD scores for Malaysian older population revealed that a stronger adherence to this diet is linked to a reduced risk of MCI. Further substantiation of the MY-MINDD scores using more objective measures, such as neuroimaging approaches and other neuropsychological batteries, is necessary.