ComBat models for harmonization of resting-state EEG features in multisite studies.

OBJECTIVE: Pooling multisite resting-state electroencephalography (rsEEG) datasets may introduce bias due to batch effects (i.e., cross-site differences in the rsEEG related to scanner/sample characteristics). The Combining Batches (ComBat) models, introduced for microarray expression and adapted for neuroimaging, can control for batch effects while preserving the variability of biological covariates. We aim to evaluate four ComBat harmonization methods in a pooled sample from five independent rsEEG datasets of young and old adults. METHODS: RsEEG signals (n = 374) were automatically preprocessed. Oscillatory and aperiodic rsEEG features were extracted in sensor space. Features were harmonized using neuroCombat (standard ComBat used in neuroimaging), neuroHarmonize (variant with nonlinear adjustment of covariates), OPNested-GMM (variant based on Gaussian Mixture Models to fit bimodal feature distributions), and HarmonizR (variant based on resampling to handle missing feature values). Relationships between rsEEG features and age were explored before and after harmonizing batch effects. RESULTS: Batch effects were identified in rsEEG features. All ComBat methods reduced batch effects and features' dispersion; HarmonizR and OPNested-GMM ComBat achieved the greatest performance. Harmonized Beta power, individual Alpha peak frequency, Aperiodic exponent, and offset in posterior electrodes showed significant relations with age. All ComBat models maintained the direction of observed relationships while increasing the effect size. CONCLUSIONS: ComBat models, particularly HarmonizeR and OPNested-GMM ComBat, effectively control for batch effects in rsEEG spectral features. SIGNIFICANCE: This workflow can be used in multisite studies to harmonize batch effects in sensor-space rsEEG spectral features while preserving biological associations.

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer's Disease: A Pragmatic Review for Clinicians.

This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer's disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

Subjective Cognitive and Communicative Complaints and Health-Related Quality of Life in Parkinson's Disease with and without Mild Cognitive Impairment.

INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.

Machine Learning-Based Detection of Parkinson's Disease From Resting-State EEG: A Multi-Center Study.

Resting-state EEG (rs-EEG) has been demonstrated to aid in Parkinson's disease (PD) diagnosis. In particular, the power spectral density (PSD) of low-frequency bands (δ and θ) and high-frequency bands (α and ß) has been shown to be significantly different in patients with PD as compared to subjects without PD (non-PD). However, rs-EEG feature extraction and the interpretation thereof can be time-intensive and prone to examiner variability. Machine learning (ML) has the potential to automatize the analysis of rs-EEG recordings and provides a supportive tool for clinicians to ease their workload. In this work, we use rs-EEG recordings of 84 PD and 85 non-PD subjects pooled from four datasets obtained at different centers. We propose an end-to-end pipeline consisting of preprocessing, extraction of PSD features from clinically-validated frequency bands, and feature selection. Following, we assess the classification ability of the features via ML algorithms to stratify between PD and non-PD subjects. Further, we evaluate the effect of feature harmonization, given the multi-center nature of the datasets. Our validation results show, on average, an improvement in PD detection ability (69.6% vs. 75.5% accuracy) by logistic regression when harmonizing the features and performing univariate feature selection (k = 202 features). Our final results show an average global accuracy of 72.2% with balanced accuracy results for all the centers included in the study: 60.6%, 68.7%, 77.7%, and 82.2%, respectively.Clinical relevance- We present an end-to-end pipeline to extract clinically relevant features from rs-EEG recordings that can facilitate the analysis and detection of PD. Further, we provide an ML system that shows a good performance in detecting PD, even in the presence of centers with different acquisition protocols. Our results show the relevance of harmonizing features and provide a good starting point for future studies focusing on rs-EEG analysis and multi-center data.

Subjective Cognitive and Communicative Complaints and Health-Related Quality of Life in Parkinson's Disease with and without Mild Cognitive Impairment / Quejas subjetivas cognitivas y comunicativas y Calidad de Vida Relacionada con la Salud en la Enfermedad de Parkinson con y Sin Deterioro Cognitivo Leve

ABSTRACT Introduction: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. Objective: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. Methods: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. Results: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. Conclusions: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psy-chotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.

RESUMEN Introducción: El deterioro cognitivo leve (DCL) es frecuente en la enfermedad de Parkinson (EP). Pocos estudios han comparado la calidad de vida relacionada con la salud (CVRS) en pacientes con DCL debido a EP (EP-DCL) sin explorar la relación entre la CVRS y las quejas subjetivas cognitivas y comunicativas de los pacientes. Objetivo: Comparar la CVRS en EP-DCL y EP sin DCL (EP-nDCL) explorando sus posibles relaciones con las quejas subjetivas cognitivas y comunicativas. Métodos: Se incluyó a 29 EP-DCL y 11 EP-nDCL. La CVRS se evaluó con el cuestionario PDQ-39: su dimensión Cognición se usó como medida de las quejas subjetivas cognitivas; su dimensión Comunicación, como medida de las quejas subjetivas comunicativas y su puntuación resumen (PDQ-39 SI), como indicador de CVRS. Se realizaron correlaciones parciales no paramétricas entre el PDQ-39 SI ajustado y las dimensiones Cognición y Comunicación. Resultados: Los pacientes EP-DCL presentaron una peor CVRS y mayores quejas subjetivas cognitivas y comunicativas. En el grupo EP-DCL, tanto las quejas subjetivas cognitivas como las comunicativas mostraron correlaciones directas significativas con la puntuación de CVRS ajustada. Conclusiones: La CVRS de los pacientes con EP-DCL parece estar afectada e influida por las quejas subjetivas en cognición y comunicación. Incluir los resultados de CVRS reportados por los pacientes, proveer rehabilitación cognitiva y del lenguaje y estrategias de psicoterapia para afrontar dicho déficit podrían mejorar el abordaje centrado en el paciente en la EP.

Specific neuropsychiatric symptoms are associated with functional decline trajectories in Alzheimer's disease and Lewy body dementia: a five-year follow-up study.

Background: Neuropsychiatric symptoms (NPS) are often overlooked and under-identified symptoms associated with dementia, despite their significant impact on the prognosis of individuals living with the disease. The specific role of certain NPS in functional prognosis remains unclear. Aims: To determine the association of different NPS with functional decline in people living with Alzheimer's disease (AD) or Lewy body dementia (LBD). Methods: This is an analysis of data from the Dementia Study of Western Norway (DemVest) with 196 patients included of which 111 had AD and 85 LBD. The Neuropsychiatric Inventory (NPI) and the Rapid Disability Rating Scale (RDRS-2) for activities of daily living were administered annually for 5 years. NPI total score and individual items with RDRS-2 trajectories were analyzed with linear mixed models. Results: The LBD group exhibited higher levels of functional impairment and a greater burden of NPS at baseline. Over the 5-year follow-up, hallucinations, aggression, depression, anxiety, apathy, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and abnormal eating patterns were significantly associated with the decline in functional abilities in individuals with AD, as well as irritability and aberrant motor behavior in those with LBD. Discussion: These results highlight the relevance of early detection and intervention of these particularly relevant NPS, due to its potential of also impacting physical function. Better detection and management of these NPS could improve functional prognosis in people living with dementia. Conclusion: Specific NPS demonstrate relevant distinct associations with Longitudinal trajectories of functional decline in AD and LBD.

Spectral features of resting-state EEG in Parkinson's Disease: A multicenter study using functional data analysis.

OBJECTIVE: This study aims 1) To analyse differences in resting-state electroencephalogram (rs-EEG) spectral features of Parkinson's Disease (PD) and healthy subjects (non-PD) using Functional Data Analysis (FDA) and 2) To explore, in four independent cohorts, the external validity and reproducibility of the findings using both epoch-to-epoch FDA and averaged-epochs approach. METHODS: We included 169 subjects (85 non-PD; 84 PD) from four centres. Rs-EEG signals were preprocessed with a combination of automated pipelines. Sensor-level relative power spectral density (PSD), dominant frequency (DF), and DF variability (DFV) features were extracted. Differences in each feature were compared between PD and non-PD on averaged epochs and using FDA to model the epoch-to-epoch change of each feature. RESULTS: For averaged epochs, significantly higher theta relative PSD in PD was found across all datasets. Also, higher pre-alpha relative PSD was observed in three of four datasets in PD patients. For FDA, similar findings were achieved in theta, but all datasets showed consistently significant posterior pre-alpha differences across multiple epochs. CONCLUSIONS: Increased generalised theta, with posterior pre-alpha relative PSD, was the most reproducible finding in PD. SIGNIFICANCE: Rs-EEG theta and pre-alpha findings are generalisable in PD. FDA constitutes a reliable and powerful tool to analyse epoch-to-epoch the rs-EEG.

Serum TCA cycle metabolites in Lewy bodies dementia and Alzheimer's disease: Network analysis and cognitive prognosis.

Abnormalities in the Tri-Carboxylic-Acid (TCA) cycle have been documented in dementia. Through network analysis, TCA cycle metabolites could indirectly reflect known dementia-related abnormalities in biochemical pathways, and key metabolites might be associated with prognosis. This study analyzed TCA cycle metabolites as predictors of cognitive decline in a mild dementia cohort and explored potential interactions with the diagnosis of Lewy Body Dementia (LBD) or Alzheimer's Disease (AD) and APOE-ε4 genotype. We included 145 mild dementia patients (LBD = 59; AD = 86). Serum TCA cycle metabolites were analyzed at baseline, and partial correlation networks were conducted. Cognitive performance was measured annually over 5-years with the Mini-mental State Examination. Longitudinal mixed-effects Tobit models evaluated each baseline metabolite as a predictor of 5-years cognitive decline. APOE-ε4 and diagnosis interactions were explored. Results showed comparable metabolite concentrations in LBD and AD. Multiple testing corrected networks showed larger coefficients for a negative correlation between pyruvate - succinate and positive correlations between fumarate - malate and citrate - Isocitrate in both LBD and AD. In the total sample, adjusted mixed models showed significant associations between baseline citrate concentration and longitudinal MMSE scores. In APOE-ε4 carriers, baseline isocitrate predicted MMSE scores. We conclude that, in mild dementia, serum citrate concentrations could be associated with subsequent cognitive decline, as well as isocitrate concentrations in APOE-ε4 carriers. Downregulation of enzymatic activity in the first half of the TCA cycle (decarboxylating dehydrogenases), with upregulation in the latter half (dehydrogenases only), might be indirectly reflected in serum TCA cycle metabolites' networks.

Frailty in Parkinson's disease and its association with early dementia: A longitudinal study.

INTRODUCTION: Frailty is recognized as a clinical condition associated with increased vulnerability for developing negative health outcomes but has been little studied in patients with Parkinson's disease (PD). Here, we investigated the risk of frailty in de novo PD patients and its association with subsequent development of dementia. METHODS: We conducted a three-year longitudinal population-based study of 192 drug-naive newly diagnosed PD patients and 172 controls (No-PD) matched for age, sex, and education. Frailty was measured using the frailty index (FI). Logistic regression models, adjusting for potential confounders, were conducted to assess the association between frailty at the time of PD diagnosis and the subsequent odds for developing PD dementia during follow-up. RESULTS: The mean baseline FI score was higher in the PD (0.21 ± 0.10) than in the No-PD group (0.11 ± 0.07, p < 0.001). One-third of PD patients had high-FI (>0,25), compared to 5% in the no-PD group. Participants with PD had an increased risk to present frailty with an odds ratio (OR) of 6.68 (SE 2.70 IC 95% [3.15; 15.62], p-value <0.001) compared to the No-PD group. PD Participants with greater FI measured at baseline had increased odds of having dementia within three years of follow-up, after adjustment for age and sex (OR 2.91 SE 1.00 IC 95% [1.54; 5.99] p-value = 0.002). CONCLUSION: Frailty is common in people with newly diagnosed PD and associated with increased odds for subsequent development of dementia in a three-year follow-up. This study emphasizes the prognostic importance of frailty in PD from the earliest clinical stages.

Body mass index trajectories and associations with cognitive decline in people with Lewy body dementia and Alzheimer's disease.

Background and Aims: In older adults with dementia, low body mass index (BMI) is associated with higher mortality and other adverse health outcomes. BMI or nutritional status trajectories from diagnosis have not yet been well described in dementia, especially in people with Lewy body dementia (LBD); a group that has a poorer prognosis. With this study, we aimed to evaluate the BMI trajectory in people diagnosed with mild LBD and Alzheimer's disease (AD). Methods: The Dementia Study of Western Norway is a cohort study with annual assessments. Five-year measurements of BMI from 196 patients (LBD = 85 and AD = 111) diagnosed with mild dementia were analyzed using adjusted linear mixed-effects models. Results: There were no differences between LBD and AD in baseline BMI, age, or mini-mental status examination (MMSE). During the follow-up, we observed a significant decrease in BMI in the LBD group across the study period (estimation [Est.]: -0.63, SE: 0.14; p < 0.001). By contrast, there was no significant change in BMI trajectory associated with AD diagnosis (Est.: 0.05, SE: 0.15; p = 0.730). Further, the introduction of an interaction term between diagnosis and time in the study showed that this difference (BMI trajectories) was significant (Est.: -0.63, SE: 0.14; p < 0.001). In addition, there was a significant interaction between MMSE total score and the follow-up time; the lower the MMSE, the lower the BMI (Est.: 0.01, SE: 0.01; p = 0.044). Conclusion: In LBD, BMI significantly decreased with disease progression. In addition, low cognitive performance was associated with a reduction in BMI. These results highlight the importance of BMI evaluation in people with dementia, particularly patients diagnosed with LBD, and suggest that patients with LBD could be targeted for dietary intervention to maintain body weight.

Prodromal Dementia With Lewy Bodies and Recurrent Panic Attacks as the First Symptom: A Case Report.

Psychiatric-onset dementia with Lewy bodies (DLB) might include symptoms of depression, hallucinations, anxiety, and apathy. Here, we report a patient with DLB with recurrent panic attacks as her first symptom 5 years before a biological-based diagnosis of probable DLB. We provide an extended description of the clinical presentation and course from psychiatric-onset DLB to dementia in an 83-year-old woman. This case illustrates the common misdiagnosis of DLB and the delay of having a detailed clinical and biomarker assessment for structured diagnosis. With a detailed description of the clinical presentation of this case, the empirical treatment strategies, and the patient perspectives, we aim to make clinicians aware of panic attacks within the psychiatric-onset DLB.

Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness.

INTRODUCTION: Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). METHODS: This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. RESULTS: The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. DISCUSSION/CONCLUSION: TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.

Muscular Function as an Alternative to Identify Cognitive Impairment: A Secondary Analysis From SABE Colombia.

BACKGROUND: Identification of cognitive impairment is based traditionally on the neuropsychological tests and biomarkers that are not available widely. This study aimed to establish the association between motor function (gait speed and handgrip strength) and cognitive performance in the Mini-Mental State Examination, globally and by domains. A secondary goal was calculating a cut-off point for gait speed and handgrip strength to classify older adults as cognitively impaired. METHODS: This is a secondary analysis of SABE Colombia (Salud, Bienestar & Envejecimiento), a survey that was conducted in 2015 on health, wellbeing, and aging in Colombia. This study used linear regression models to search for an association between motor function and cognitive performance. The accuracy of motor function measurements in identifying cognitive impairment was assessed with receiver operating characteristic (ROC) curves. This study also analyzed other clinical and sociodemographical variables. RESULTS: Gait speed was associated with orientation (r 2 = 0.16), language (r 2 = 0.15), recall memory (r 2 = 0.14), and counting (r 2 = 0.08). Similarly, handgrip strength was associated with orientation (r 2 = 0.175), language (r 2 = 0.164), recall memory (r 2 = 0.137), and counting (r 2 = 0.08). To differentiate older adults with and without cognitive impairment, a gait speed cut-off point of 0.59 m/s had an area under the curve (AUC) of 0.629 (0.613-0.646), and a weak handgrip (strength below 17.5 kg) had an AUC of 0.653 (0.645-0.661). The cut-off points for handgrip strength and gait speed were significantly higher in male participants. CONCLUSIONS: Gait speed and handgrip strength are similarly associated with the cognitive performance, exhibiting the most extensive association with orientation and language domains of the Mini-Mental State Examination. Gait speed and handgrip strength can easily be measured by any clinician, and they prove to be useful screening tools to detect cognitive impairment.

Subjective Cognitive and Communicative Complaints and Health-Related Quality of Life in Parkinson's Disease with and without Mild Cognitive Impairment.

INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.

Association Between Amygdala Volume and Trajectories of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia With Lewy Bodies.

Introduction: The amygdala is implicated in psychiatric illness. Even as the amygdala undergoes significant atrophy in mild dementia, amygdala volume is underexplored as a risk factor for neuropsychiatric symptoms (NPS). Objective: To analyze the association between baseline amygdala volume and the longitudinal trajectories of NPS and cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) over 5 years. Methods: Eighty-nine patients with mild dementia were included (AD = 55; DLB = 34). Amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi-automatic method (Freesurfer 6.0) and normalized by intracranial volumes. The intracranial volume-normalized amygdala was used as a predictor of the Neuropsychiatric Inventory (NPI) total score, ordinal NPI item scores (0 = absence of symptoms, 1-3 = mild symptoms, ≥4 = clinically relevant symptoms), and Mini-Mental State Examination (MMSE) as measured annually over 5 years using gamma, ordinal, and linear mixed-effects models, respectively. The models were adjusted for demographic variables, diagnosis, center of sMRI acquisition, and cognitive performance. Multiple testing-corrected p-values (q-values) are reported. Results: Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90], p = 0.011, q = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03], p = 0.001, q = 0.010) but more depression (OR = 1.49 [1.09, 2.04], p = 0.013, q = 0.040). Conclusions: Greater amygdala volume in mild dementia is associated with lower odds of developing agitation/aggression, but higher odds of developing depression symptoms during the 5-year study period.

Quality of life in early-onset Alzheimer's disease due to a PSEN1-E280A mutation.

PURPOSE: The present study aims to explore the association between the quality of life (QoL) score and the clinical and sociodemographic variables in patients with the PSEN1-E280A mutation. We also seek to evaluate the differences between the QoL reported by the patients (P-QoL) and the scores reported by the caregivers (C-QoL). METHODS: An analysis of 75 patients with the PSEN1-E280A mutation with mild cognitive impairment and dementia was performed. We used the Quality of Life in Alzheimer Disease (QoL-AD) survey to evaluate QoL as an outcome and evaluated its association with sociodemographic, lifestyle, clinical, and past medical history variables. RESULTS: The largest difference in the median of the QoL-AD score was in those who needed help to eat, those with moderate or severe dementia, those classified as frail or pre-frail, those with moderate social risk, and those with depression. Also, C-QoL was lower than the P-QoL, and the QoL-AD of individuals with severe dementia was lower than for milder forms of the disease. Not needing help to eat, not having a stressful situation in the past 3 months, and the years of education were positively correlated with QoL-AD in the linear model. CONCLUSION: As studies in similar populations with AD, factors with more impact on QoL are those related to loss of functionality and independence. These factors are also associated with variables related to the current literature with the burden of the disease for the caregivers.

Body mass index, performance on activities of daily living and cognition: analysis in two different populations.

BACKGROUND: With this study, we aim to determine the associations of the different categories of the body mass index (BMI) with activities of daily living (ADL) and cognitive performance in two different populations living in the community; Colombian and South Korean older adults. METHODS: We performed a cross-sectional analysis of two surveys separately; The Survey on Health, Well-Being, and Aging in Colombia (SABE) (n = 23,343) and the Korean Longitudinal Study of aging (KLoSA) (n = 4556). Participants older than 50 years were selected from rural and urban areas achieving a representative sample. Here we investigated the association between BMI categories with function using zero-inflated negative binomial regressions, and with cognition using logistic regression models. RESULTS: After adjustment, in Colombia, underweight was associated with an impaired score on the Mini-mental State Examination (MMSE) and worse performance in the instrumental activities of daily living (IADL). Also, being overweight was associated with a better score on the MMSE and the IADL. For both outcomes education level significantly influenced the predictions. In South Korea, there were no significant associations for cognition, IADL, or basic activities of daily living (BADL). CONCLUSIONS: In the Colombian population, underweight, was associated with reduced cognitive performance and daily functioning. Additionally, being overweight but not obese was associated with better cognition and daily functioning. In South Korea, there were no significant associations between BMI and cognition, IADL, or BADL.

Resting-state EEG alpha/theta ratio related to neuropsychological test performance in Parkinson's Disease.

OBJECTIVE: To determine possible associations of hemispheric-regional alpha/theta ratio (α/θ) with neuropsychological test performance in Parkinson's Disease (PD) non-demented patients. METHODS: 36 PD were matched to 36 Healthy Controls (HC). The α/θ in eight hemispheric regions was computed from the relative power spectral density of the resting-state quantitative electroencephalogram (qEEG). Correlations between α/θ and performance in several neuropsychological tests were conducted, significant findings were included in a moderation analysis. RESULTS: The α/θ in all regions was lower in PD than in HC, with larger effect sizes in the posterior regions. Right parietal, and right and left occipital α/θ had significant positive correlations with performance in Judgement of Line Orientation Test (JLOT) in PD. Adjusted moderation analysis indicated that right, but not left, occipital α/θ influenced the JLOT performance related to PD. CONCLUSIONS: Reduction of the occipital α/θ, in particular on the right side, was associated with visuospatial performance impairment in PD. SIGNIFICANCE: Visuospatial impairment in PD, which is highly correlated with the subsequent development of dementia, is reflected in α/θ in the right posterior regions. The right occipital α/θ may represent a useful qEEG marker for evaluating the presence of early signs of cognitive decline in PD and the subsequent risk of dementia.

Association of Malnutrition with Functional and Cognitive Trajectories in People Living with Dementia: A Five-Year Follow-Up Study.

BACKGROUND: In dementia, functional status depends on multiple factors in addition to cognition. Nutritional status is a potentially modifiable factor related to homeostasis and proper functioning of body systems and may contribute to cognitive and functional decline. OBJECTIVE: This paper aims to analyze the association of malnutrition with the course of cognitive and functional decline in people living with dementia. METHODS: This is an analysis of a longitudinal cohort study, the Dementia Study of Western Norway. Data of 202 patients diagnosed with mild dementia were analyzed; Alzheimer's disease (AD) (n = 103), Lewy body dementia (LBD) (n = 74), and other dementias (OD) (n = 25). Cognition was assessed with the Mini-Mental State Examination and functional decline through the activities of daily living included in the Rapid Disability Rating Scale. The Global Leadership Initiative on Malnutrition Index was used to determine nutritional status. Associations of nutritional status with cognitive and functional decline were evaluated through adjusted linear mixed models. RESULTS: At baseline, the prevalence of general malnutrition was 28.7%; 17.3% were classified as moderate malnutrition and 11.38% as severe malnutrition (there were no significant differences between AD and LBD). Malnutrition at diagnosis and over follow-up was a significant predictor of functional-decline, but not of cognitive decline. CONCLUSION: According to our results malnutrition was associated with faster functional loss but, not cognitive decline in older adults with dementia. A more comprehensive dementia approach including nutritional assessments could improve prognosis.

Benzodiazepines and antidepressants: Effects on cognitive and functional decline in Alzheimer's disease and Lewy body dementia.

OBJECTIVES: We aim to study the effects of the prescription of benzodiazepines and antidepressants on cognitive and functional decline in older adults living with Alzheimer's disease (AD) and Lewy body dementia (LBD) over a 5-year follow-up. METHODS: This is a longitudinal analysis of a Norwegian cohort study entitled "The Dementia Study of Western Norway" (DemVest). We included 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed annually for 5 years. Three prescription groups were defined: only benzodiazepines (BZD), only antidepressants (ADep), and the combination of benzodiazepines and antidepressants (BZD-ADep). Linear mixed-effects models were conducted to analyze the effect of the defined groups on the outcomes. The outcomes were functional decline, measured by the Rapid Disability Rating Scale-2, and cognition measured with the Mini-Mental State Examination. RESULTS: Prescription of the combination of benzodiazepines and antidepressants in LBD was associated with faster functional decline. In AD, the prescription of BZD and BZD-ADep was associated with greater functional deterioration. ADep alone did not show positive or negative significant associations with the studied outcomes. CONCLUSIONS: BZD and especially the combination of BZD and ADep are associated with functional decline in AD and LBD and should be used cautiously.