Non-demented Patients Research Articles

Mental State Recognition Deficits Linked to Brain Changes in Parkinson's Disease Without Dementia.

Recent studies have reported social cognitive deficits, particularly in emotional processing, in Parkinson's disease (PD). However, a comprehensive characterization of these deficits and their underlying neural correlates remains elusive. Therefore, this study aims to investigate the association between deficits in the recognition of complex mental states and structural/functional brain changes in non-demented PD individuals. To reach this aim, 24 PD participants underwent clinical assessment, neuropsychological testing and the FAcial Complex Expressions (FACE) test, a novel test of complex mental state recognition from faces. Patients were classified as clinically impaired (n = 8) or unimpaired (n = 16) based on performance on this test. Magnetic resonance imaging data were acquired to investigate the association between FACE test performance and both resting-state functional connectivity and grey matter volume, within the emotion understanding network and at the whole-brain level. Statistical analyses also included the comparison of imaging metrics between the impaired and unimpaired groups. Results showed that complex mental state recognition in PD was significantly associated with both defective and compensatory mechanisms at the functional and anatomical level within the emotion understanding network, particularly involving the amygdala, dorsomedial prefrontal cortex, primary/secondary somatosensory cortices, and right anterior temporal cortex. Whole-brain results extended the network to temporal and medial frontal areas. In conclusion, reduced recognition of complex mental states in non-demented PD patients is associated with alterations in the emotion understanding network A comprehensive characterization of early emotional deficits in these patients may have significant implications in the characterization of the cognitive phenotype, with potential benefit for tailored non-pharmacological intervention.

Effects of a daylight intervention in the morning on circadian rhythms and sleep in geriatric patients: a randomized crossover trial

During hospitalization, circadian rhythms and sleep are often disrupted, which has negative effects on health outcomes. Therefore, we aimed to investigate whether a daylight intervention in the morning could improve the circadian rhythms of cortisol and melatonin and enhance objective and subjective sleep quality in geriatric patients. The present study is a randomized, two-period crossover trial conducted in a geriatric ward in 15 non-demented geriatric trauma patients with a mean age of 83.1 ± 5.4years. All patients underwent a daylight intervention period, during which they were exposed to a daylight lamp from 8:00 to 13:00h, and a control period of 6days each. Cortisol and melatonin levels were measured on day 5 of each period. Objective and subjective sleep quality were assessed using actigraphy and questionnaires, respectively. Within-participant differences between periods were investigated for all parameters. A trend towards improvement in cortisol and melatonin rhythmicity was found. An increase in mean melatonin levels from 0.3 ± 0.1 to 0.9 ± 0.8ng/L was observed during the intervention period (p = .063). There was also a trend towards increased sleep efficiency, whereas subjective sleep quality tended to decrease. None of the results were significant. A daylight intervention in the morning led to a positive trend in cortisol and melatonin rhythmicity, whereas no improvement in subjective sleep quality was found. DRKS00028626 at German Clinical Trials Register, 13.06.2022.

Highly prevalent geriatric medications and their effect on β-amyloid fibril formation

BackgroundThe unprecedented increase in the older population and ever-increasing incidence of dementia are leading to a “silver tsunami” in upcoming decades. To combat multimorbidity and maintain daily activities, elderly people face a high prevalence of polypharmacy. However, how these medications affect dementia-related pathology, such as Alzheimer’s β-amyloid (Aβ) fibrils formation, remains unknown. In the present study, we aimed to analyze the medication profiles of Alzheimer’s disease (AD; n = 124), mild cognitive impairment (MCI; n = 114), and non-demented (ND; n = 228) patients to identify highly prevalent drugs and to determine the effects of those drugs on Aβ fibrils formation.MethodsStudy subjects (≥ 65 years) were recruited from an academic geriatric practice that heavily focuses on memory disorders. The disease state was defined based on the score of multiple cognitive assessments. Individual medications for each subject were listed and categorized into 10 major drug classes. Statistical analysis was performed to determine the frequency of individual and collective drug classes, which are expressed as percentages of the respective cohorts. 10 µM monomeric β-amyloid (Aβ) 42 and fibrillar Aβ (fAβ) were incubated for 6–48 h in the presence of 25 µM drugs. fAβ was prepared with a 1:10 ratio of Aβ42 to Aβ40. The amount of Aβ fibrils was monitored using a thioflavin T (Th-T) assay. Neuronal cells (N2A and SHSY-5Y) were treated with 25 µM drugs, and cell death was measured using a lactose dehydrogenase (LDH) assay.ResultsWe noticed a high prevalence (82–90%) of polypharmacy and diverse medication profiles including anti-inflammatory (65–77%), vitamin and mineral (64–72%), anti-cholesterol (33–41%), anti-hypersensitive (35–39%), proton pump inhibitor (23–34%), anti-thyroid (9–21%), anti-diabetic (5–13%), anti-constipation (9–11%), anti-coagulant (10–13%), and anti-insomnia (9–20%) drugs in the three cohorts. Our LDH assay with 18 highly prevalent drug components showed toxic effects of Norvasc, Tylenol, Colace, and Plavix on N2A cells, and of vitamin D and Novasc on SH-SY5Y cells. All these drugs except Colace significantly reduced the amount of Aβ fibril when incubated with Aβ42 for a short period (6 h). However, Lipitor, vitamin D, Levothyroxine, Prilosec, Flomax, and Norvasc prominently reduce the amount of fibrils when incubated with monomeric Aβ42 for a longer period (48 h). Furthermore, our disaggregation study with fAβ showed consistent results for cholecalciferol (vitamin D), omeprazole (Prilosec), clopidogrel hydrogensulfate (Flomax), levothyroxine, and amlodipine (Norvasc). The chemical structures of these four efficient molecules contain polyphenol components, a characteristic feature of the structures of polyphenolic inhibitors of Aβ fibrillation.ConclusionA higher polypharmacy incidence was observed in an elderly population of 228 ND, 114 MCI, and 124 AD patients. We found that several highly recommended drug components, including vitamin D3, Levothyroxine, Prilosec, Flomax, and Norvasc, efficiently reduce the amount of fibrils formed by monomeric Aβ42 and existing preformed Aβ fibrils in vitro. However, only Levothyroxine was able to prevent Aβ-mediated toxicity to SH-SY5Y cells. Our study suggested that these drugs likely function as polyphenolic inhibitors of Aβ.

Gait abnormalities and longitudinal fall risk in older patients with end-stage kidney disease and sarcopenia

BackgroundSarcopenia, gait disturbance, and intradialytic hypotension are among the various factors that contribute to fall risk. This study aimed to investigate the relationship between risk of sarcopenia, hemodialysis (HD) session, and long-term fall risk in older end-stage kidney disease (ESKD) patients by analyzing their spatiotemporal gait characteristics.MethodsWe recruited 22 non-demented patients aged ≥ 65 years who were undergoing maintenance HD. Participants were divided into two groups based on their SARC-F score (< 4 and ≥ 4) to identify those with higher and lower risk of sarcopenia. Demographics, comorbidities, and renal parameters were compared between groups. Inertial measurement unit-based technology equipped with triaxial accelerometry and gyroscope was used to evaluate gait characteristics. The gait task was assessed both before and after dialysis using the Timed-Up and Go (TUG) test and a 10-meter walking test at a regular pace. Essential gait parameters were thoroughly analyzed, including gait speed, stride time, stride length, double-support phase, stability, and symmetry. We investigated the interaction between the dialysis procedure and gait components. Outcome of interest was any occurrence of injurious fall during follow-up period. Logistic regression models were employed to examine the relationship between baseline gait markers and long-term fall risk.ResultsThe SARC-F ≥ 4 group showed various gait abnormalities, including longer TUG time, slower gait speed, longer stride time, shorter stride length, and longer double support time compared to counterpart (SARC-F < 4). After HD sessions, the SARC-F ≥ 4 group showed a 2.0-second decrease in TUG task time, an 8.0 cm/s increase in gait speed, an 11.6% lower stride time, and a 2.4% increase in gait symmetry with significant group-time interactions. Shorter stride length and longer double support time were associated with injurious falls during the two-year follow-up.ConclusionOur study demonstrated the utility of triaxial accelerometers in extracting gait characteristics in older HD patients. High-risk sarcopenia (SARC-F ≥ 4) was associated with various gait abnormalities, some of which partially improved after HD sessions. These gait abnormalities were predictive of future falls, highlighting their prognostic significance.

Fear among patients with Parkinson's disease and repeated falls: Analysis of skin conductance responses during simulated accidents

Fear among patients with Parkinson's disease and repeated falls: Analysis of skin conductance responses during simulated accidents

Reliable change indices for the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson’s disease patients

Background. The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson’s disease (PD) patients.MethodsN = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval (M = 6.6; SD = 0.6) with the MoCA. Practice effects and test-retest reliability were assessed via dependent-sample t-tests and intra-class correlation (ICC) coefficients, respectively. RCIs were derived separately for raw and demographically adjusted MoCA scores according to a standardized regression-based approach by accounting for both baseline confounders (i.e., demographics, disease duration and Unified Parkinson’s Disease Rating Scale scores) and retest interval.ResultsNo practice effects were found (t(32) = 0.29; p = .778), with acceptable test-retest reliability being detected (ICC = 0.67). MoCA scores at T0 proved to be the only significant predictor of T1 MoCA performances within both the model addressing raw scores and that addressing adjusted scores (ps < 0.001).ConclusionsThe present study provides Italian practitioners and researchers with regression-based RCIs for the MoCA in non-demented PD patients, which can be reliably adopted for retest interval ≥ 5 and ≤ 8 months without encountering any practice effect.

Mild cognitive impairment in amyotrophic lateral sclerosis: current view.

Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.

Clinical usefulness of the Verbal Fluency Index (VFI) in amyotrophic lateral sclerosis.

This study aimed at assessing the clinical utility of the Verbal Fluency Index (VFI) over a classical phonemic verbal fluency test in Italian-speaking amyotrophic lateral sclerosis (ALS) patients. N = 343 non-demented ALS patients and N = 226 healthy controls (HCs) were administered the Verbal fluency - S task from the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The associations between the number of words produced (NoW), the time to read words aloud (TRW) and the VFI (computed as [(60"-TRW)/NoW]) on one hand and both bulbar/respiratory scores from the ALS Functional Rating Scale - Revised (ALSFRS-R) and the ECAS-Executive on the other were tested. Italian norms for the NoW and the VFI were derived in HCs via the Equivalent Score method. Patients were classified based on their impaired/unimpaired performances on the NoW and the VFI (NoW-VFI-; NoW-VFI+; NoW + VFI-; NoW + VFI+), with these groups being compared on ECAS-Executive scores. The VFI, but neither the NoW nor the TRW, were related to ALSFRS-Bulbar/-Respiratory scores; VFI and NoW measures, but not the TRW, were related to the ECAS-Executive (p < .001). The NoW slightly overestimated the number of executively impaired patients when compared to the VFI (31.1% vs. 26.8%, respectively). Patients with a defective VFI score - regardless of whether they presented or not with a below-cutoff NoW - reported worse ECAS-Executive scores than NoW + VFI + ones. The present reports support the use of the Italian VFI as a mean to validly assess ALS patients' executive status by limiting the effect of motor disabilities that might undermine their speech rate.

Development and assessment of algorithms for predicting brain amyloid positivity in a population without dementia

BackgroundThe accumulation of amyloid-β (Aβ) peptide in the brain is a hallmark of Alzheimer’s disease (AD), occurring years before symptom onset. Current methods for quantifying in vivo amyloid load involve invasive or costly procedures, limiting accessibility. Early detection of amyloid positivity in non-demented individuals is crucial for aiding early AD diagnosis and for initiating anti-amyloid immunotherapies at early stages. This study aimed to develop and validate predictive models to identify brain amyloid positivity in non-demented patients, using routinely collected clinical data.MethodsPredictive models for amyloid positivity were developed using data from 853 non-demented participants in the MEMENTO cohort. Amyloid levels were measured potentially repeatedly during study course through Positron Emision Tomography or CerebroSpinal Fluid analysis.The probability of amyloid positivity was modelled using mixed-effects logistic regression. Predictors included demographic information, cognitive assessments, visual brain MRI evaluations of hippocampal atrophy and lobar microbleeds, AD-related blood biomarkers (Aβ42/40 and P-tau181), and ApoE4 status. Models were subjected to internal cross-validation and external validation using data from the Amsterdam Dementia Cohort. Performance also was evaluated in a subsample that met the main criteria of the Appropriate Use Recommendations (AUR) for lecanemab.ResultsThe most effective model incorporated demographic data, cognitive assessments, ApoE status, and AD-related blood biomarkers, achieving AUCs of 0.82 [95%CI 0.81-0.82] in MEMENTO sample and 0.90 [95%CI 0.86-0.94] in the external validation sample. This model significantly outperformed a reference model based solely on demographic and cognitive data, with an AUC difference in MEMENTO of 0.10 [95%CI 0.10-0.11]. A similar model without ApoE genotype achieved comparable discriminatory performance. MRI markers did not improve model performance. Performances in AUR of lecanemab subsample were comparable.ConclusionA predictive model integrating demographic, cognitive, and blood biomarker data offers a promising method to help identify amyloid status in non-demented patients. ApoE genotype and brain MRI data were not necessary for strong discriminatory ability, suggesting that ApoE genotyping may be deferred when assessing the risk-benefit ratio of immunotherapies in amyloid-positive patients who desire treatment. The integration of this model into clinical practice could reduce the need for lumbar puncture or PET examinations to confirm amyloid status.

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

Body image appearance in Parkinson's disease patients on device aided therapies.

Parkinson's disease patients may experience altered body image perception. Advanced Parkinson's disease (aPD) with motor complications often requires surgical and device-aided treatments (DAT), such as levodopa-carbidopa intestinal gel (LCIG) and deep brain stimulation (DBS). Understanding body image perception is crucial when managing these devices. This study aims to explore body image perception in aPD patients, hypothesizing a link between DAT and body image perception. We performed a cross-sectional study including non-demented aPD patients with and without DAT and age- and sex-matched controls. Participants were assessed using the Appearance Schemas Inventory-Revised (ASI-R), including Motivational Salience (MS) and Self-Evaluative Salience (SES) scores. Additional data included age, education, BMI, comorbidities, pharmacotherapy, and psychopathologies. PD patients were also evaluated with UPDRS, Hoehn and Yahr scales and LEDD calculation. 70 aPD and 36 controls were enrolled. No differences in ASI-R scores were found between PD patients and controls, but women with PD had significantly lower MS scores than controls (16.1 ± 5.6 vs 19.7 ± 5.8; p = 0.023). Among aPD patients, those on DAT had longer disease duration, higher Hoehn and Yahr, and lower UPDRS IV scores. The lowest MS was observed in women on LCIG (12.7 ± 3.3; p = 0.001). This study shows low MS ratings driven by female gender and LCIG treatment. Women on LCIG show reduced attention and management of their appearance. This may be influenced by cultural, environmental, and biological factors. Prospective research is needed to understand the impact of DAT on body image.

Correlation between dopaminergic and metabolic asymmetry in Lewy body disease – A dual-imaging study

IntroductionThe a-Synuclein Origin and Connectome (SOC) model of Lewy body diseases postulates that a-syuclein will be asymmetrically distributed in some patients with Lewy body diseases, potentially leading to asymmetric neuronal dysfunction and symptoms. MethodsWe included two patient groups: 19 non-demented Parkinson's disease (nPD) patients with [18F]FDG PET and motor symptoms assessed by UPDRS-III, and 65 Lewy body dementia (LBD) patients with [18F]FDG PET and dopamine radioisotope imaging. Asymmetry indices were calculated for [18F]FDG PET by including the cortex for each hemisphere, for dopamine radioisotope imaging by including the putamen and caudate separately, and for motor symptoms by using the difference between right-left UPDRS-III score. Correlations between these asymmetry indices were explored to test the predictions of the SOC model. To identify cases with a more typical LBD imaging profile, we calculated a Cingulate Island Sign (CIS) index on the [18F]FDG PET image. ResultsWe found a significant correlation between cortical interhemispheric [18F]FDG asymmetry and motor-symptom asymmetry in nPD patients (r = 0.62, P = 0.004). In patients with LBD, we found a significant correlation between cortical interhemispheric [18F]FDG asymmetry and dopamine transporter asymmetry in the caudate (r = 0.37, P = 0.0019), but not in the putamen (r = 0.15, P = 0.22). We observed that the correlation in the caudate was stronger in LBD subjects with the highest CIS index, i.e., with more typical LBD imaging profiles. ConclusionOur study partly supports the SOC model, but further investigations are needed – ideally of de novo, non-demented PD patients.

Amyloid-Negative, Neurodegeneration-Negative Amnestic Mild Cognitive Impairment.

The concept of amnestic mild cognitive impairment (aMCI) was developed to identify patients at an initial stage of Alzheimer's disease (AD). However, some patients with aMCI do not present biomarkers of amyloid pathology or neuronal injury. To know the natural history of amyloid-negative and neurodegeneration-negative patients with aMCI, namely to ascertain: 1) whether these patients remain cognitively stable or they present a slow decline in neuropsychological tests; 2) whether the memory complaints subside with the apparently benign clinical course of the disorder or if they persist along the time. Patients who fulfilled criteria for aMCI with no biomarkers of amyloid pathology or neuronal injury were selected from a large cohort of non-demented patients with cognitive complaints, and were followed with clinical and neuropsychological assessments. Twenty-one amyloid-negative and neurodegeneration-negative aMCI patients were followed for 7.1±3.7 years. At the baseline they had more pronounced deficits in verbal learning (California Verbal Learning Test) and were also impaired in Word Recall and Logical Memory. However, they did not decline in any cognitive test during follow-up. The patients maintained a high level of subjective memory complaints from baseline (9.7±4.1) to the follow-up visit (9.2±4.1, a non-significant difference), in spite of a statistically significant decrease in the depressive symptoms, with Geriatric Depression Scale (15 items) score 4.9±2.8 at baseline and 3.2±1.8 at the follow-up visit. Amyloid-negative, neurodegeneration-negative aMCI is a chronic clinical condition characterized by the long-term persistence of cognitive deficits and distressing memory complaints. Adequate strategies to treat this condition are needed.

Factors associated with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) alteration at time of diagnosis, in amyotrophic lateral sclerosis

Factors associated with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) alteration at time of diagnosis, in amyotrophic lateral sclerosis

Emotional awareness in patients with amyotrophic lateral sclerosis.

It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS). Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20). Patients were assessed for the identification of motor-phenotypes and frontotemporal syndromes based on current classification criteria. Spearman's coefficients explored the correlates of TAS-20 measures with motor-functional profiles, global cognitive, social-cognitive (emotion recognition and empathy) and behavioral status. Abnormal TAS-20 scores were found in 13% of patients, and their distribution did not vary within motor and frontotemporal phenotypes. Significant associations were detected between TAS-20 and executive (p ≤ .011), memory (p = .006), state-anxiety (p ≤ .013) and depression measures (p ≤ .010). By contrast, TAS-20 scores were unrelated to social-cognitive performances, dysexecutive and apathetic profiles. Disease duration was the only motor-functional feature being related to the TAS-20 (p ≤ .008). Alexithymia of potential clinical relevance occur in a minority of ALS patients, and its neuropsychological correlates mostly resemble those featuring the general population. Hence, it is unlikely that alexithymia is a specific feature of frontotemporal-spectrum characterizing ALS, rather it could be an expression of psychogenic factors as a reaction to the disease.

Levodopa modulates semantic fluency and uniqueness in non-demented patients with progressive supranuclear palsy.

Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well-established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words' uniqueness in patients with PSP. Twenty-seven patients with PSP Richardson's syndrome (PSP-RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio-recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity. The PSP-RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP-RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP-RS. The PSP-RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words. These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP-RS.

Unusual Predominant Memory Decline in an Early-Stage CADASIL Patient: A Four-Year Longitudinal Follow-Up of Hereditary Vascular Dementia

Introduction: Deficits in executive function and processing speed have traditionally been viewed as the chief cognitive manifestation of vascular contributions to cognitive impairment and dementia. This case study describes the longitudinal progression of cognitive symptoms in a 42-year-old Colombian woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary condition leading to the early onset of cerebral small vessel disease. Because of the young age of onset of vascular cognitive impairment, CADASIL allows examining the early cognitive consequences of cerebrovascular changes in the absence of age-related comorbidities. Methods: We followed the neuropsychological progression of a non-demented and stroke-free patient carrying a CADASIL mutation, in parallel to that of 13 non-carrier control subjects. At baseline, all subjects completed detailed clinical, neurological, and neuropsychological evaluations as well as an MRI scan. After a period of four years, subjects completed a follow-up neuropsychological evaluation. Results: Examination of the patient’s baseline MRI revealed the presence of significant areas of white matter hyperintensity. The patient did not present cerebral microbleeds, lacunes, notable brain atrophy, or evidence of previous strokes. In contrast to non-carrier subjects, the patient experienced predominant memory decline, with relatively preserved executive function and processing speed. Conclusions: This case highlights the heterogeneity of cognitive deficits associated with cerebrovascular disease.

Ecological validity of performance-based cognitive screeners in amyotrophic lateral sclerosis: preliminary evidence.

This study aimed at preliminarily assessing, in a cohort of non-demented amyotrophic lateral sclerosis (ALS) patients, the ecological validity, and more specifically the veridicality, of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioral Screen (ALS-CBS™), by relating their scores to caregiver-report ratings of cognitive changes. N = 147 patient-caregiver dyads were recruited. Patients were administered the ECAS and ALS-CBS™, whilst caregiver the Caregiver Behavioral Questionnaire (CBQ) and Beaumont Behavioural Inventory (BBI). An Ecological Cognitive Functioning Index (ECFI) was derived from those items of the CBQ and BBI that tap on executive and language changes. Ecological validity was assessed via both correlational and predictive analyses net of caregiver-rated behavioural changes (as assessed by the ECAS-Carer Interview). The ECFI was associated with the total scores on both the ECAS (p = .014) and ALS-CBS™ (p = .017). When looking at ECAS and ALS-CBS™ subscales, those assessing verbal fluency were selectively associated with the ECFI. The ECFI was higher in patients performing defectively on the ECAS (p = .004) and on the ALS-CBS™ (p = .027). This study suggests that both the ECAS and the ALS-CBS™ represent a valid estimate of non-demented ALS patients' cognitive status in the real world, also highlighting the clinical relevance of cognitive changes reported by caregivers.

Combined Effect of Red Wine and Mocha Pot Coffee in Mild Vascular Cognitive Impairment

Combined Effect of Red Wine and Mocha Pot Coffee in Mild Vascular Cognitive Impairment

Unveiling metabolic patterns in dementia: Insights from high-resolution quantitative blood-oxygenation-level-dependent MRI.

Oxygen extraction fraction (OEF) and deoxyhemoglobin (DoHb) levels reflect variations in cerebral oxygen metabolism in demented patients. Delineating the metabolic profiles evident throughout different phases of dementia necessitates an integrated analysis of OEF and DoHb levels. This is enabled by leveraging high-resolution quantitative blood oxygenation level dependent (qBOLD) analysis of magnitude images obtained from a multi-echo gradient-echo MRI (mGRE) scan performed on a 3.0 Tesla scanner. Achieving superior spatial resolution in qBOLD necessitates the utilization of an mGRE scan with only four echoes, which in turn limits the number of measurements compared to the parameters within the qBOLD model. Consequently, it becomes imperative to discard non-essential parameters to facilitate further analysis. This process entails transforming the qBOLD model into a format suitable for fitting the log-magnitude difference (L-MDif) profiles of the four echo magnitudes present in each brain voxel. In order to bolster spatial specificity, the log-difference qBOLD model undergoes refinement into a representative form, termed as r-qBOLD, particularly when applied to class-averaged L-MDif signals derived through k-means clustering of L-MDif signals from all brain voxels into a predetermined number of clusters. The agreement between parameters estimated using r-qBOLD for different cluster sizes is validated using Bland-Altman analysis, and the model's goodness-of-fit is evaluated using a -test. Retrospective MRI data of Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented patients without neuropathological disorders, pacemakers, other implants, or psychiatric disorders, who completed a minimum of three visits prior to MRI enrolment, are utilized for the study. Utilizing a cohort comprising 30 demented patients aged 65-83 years in stages 4-6 representing mild, moderate, and severe stages according to the clinical dementia rating (CDR), matched with an age-matched non-demented control group of 18 individuals, we conducted joint observations of OEF and DoHb levels estimated using r-qBOLD. The observations elucidate metabolic signatures in dementia based on OEF and DoHb levels in each voxel. Our principal findings highlight the significance of spatial patterns of metabolic profiles (metabolic patterns) within two distinct regimes: OEF levels exceeding the normal range (S1-regime), and OEF levels below the normal range (S2-regime). The S1-regime, accompanied by low DoHb levels, predominantly manifests in fronto-parietal and perivascular regions with increase in dementia severity. Conversely, the S2-regime, accompanied by low DoHb levels, is observed in medial temporal (MTL) regions. Other regions with abnormal metabolic patterns included the orbitofrontal cortex (OFC), medial-orbital prefrontal cortex (MOPFC), hypothalamus, ventro-medial prefrontal cortex (VMPFC), and retrosplenial cortex (RSP). Dysfunction in the OFC and MOPFC indicated cognitive and emotional impairment, while hypothalamic involvement potentially indicated preclinical dementia. Reduced metabolic activity in the RSP suggested early-stage AD related functional abnormalities. Integrated analysis of OEF and DoHb levels using r-qBOLD reveals distinct metabolic signatures across dementia phases, highlighting regions susceptible to neuronal loss, vascular involvement, and preclinical indicators.