Determinants of Post-Operative Cognitive Decline in Elderly People.

BACKGROUND: Surgery and anesthesia can result in temporary or permanent deterioration of the cognitive functions, for which causes remain unclear. OBJECTIVES: In this pilot study, we analyzed the determinants of cognitive decline following a non-emergency elective prosthesis implantation surgery for hip or knee. DESIGN: Prospective single-center study investigating psychomotor response time and changes in MoCA scores between the day before (D-1) and 2 days after (D+2) following surgery at the Lariboisière Hospital (Paris, France). PARTICIPANTS: 60 patients (71.9±7.1-year-old, 72% women) were included. MEASUREMENTS: Collected data consisted in sociodemographic data, treatments, comorbidities and the type of anesthesia (local, general or both). Furthermore, we evaluated pain and well-being before as well as after the surgery using point scales. RESULTS: Post-operative (D+2) MoCA scores were significantly lower than pre-operative ones (D-1) with a median difference of 2 pts [IQR]=4pts, (p<0.001), we found no significant difference between locoregional and general anesthesia. Pre-operative benzodiazepine or anticholinergic treatments were also associated to a drop in MoCA scores (p=0.006). Finally, the use of ketamine during anesthesia (p=0.043) and the well-being (p=0.006) evaluated before intervention, were both linked to a reduced cognitive impact. CONCLUSION: In this pilot study, we observed a post-operative short-term cognitive decline following a lower limb surgery. We also identified pre and perioperative independent factors linked to cognitive decline following surgery. In a next stage, a larger cohort should be used to confirm the impact of these factors on cognitive decline.

Chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated traumatic brain injury (TBI). This disorder is mainly observed in subjects at risk for brain traumatisms including boxers, American football and European football (soccer) players, as well as war veterans. Neuropathological findings are marked by abnormally phosphorylated tau accumulations at the depth of cerebral sulci, as well as TDP43, Aß and α-synuclein positive staining. It has been described 3 clinical variants: the behavioural/mood variant, the cognitive variant and the mixed behavioural/cognitive variant. Cerebral MRI revealed signs of diffuse atrophy with abnormal axonal findings using the diffusion tensor imaging methods. Cerebral PET tau revealed increased standardised uptake value ratio (SUVR) levels in various brain regions of CTE patients compared to controls. The place of CTE among other neurodegenerative diseases is still debated. The focus of CTE management must be on prevention. The best way to prevent CTE in athletes is to put in place strict and appropriate measures by physicians. An individual with concussion should not be allowed to play again immediately (and sometimes never) in cases of abnormal neurological symptoms or imaging abnormalities.

Association of big-5 personality traits with cognitive impairment and dementia: a longitudinal study.

BACKGROUND: Personality traits have been liked to cognitive outcomes such as dementia, but whether these associations are robust to the effects of third variables remains the subject of debate. We examined the role of socioeconomic status, depression (history and depressive symptoms), health behaviours and chronic conditions in the association of the big-5 personality traits with cognitive performance, cognitive impairment and incidence of dementia. METHODS: Data on 6135 persons (30% women), aged 60-83 years in 2012/13, are drawn from the Whitehall II Study. Participants responded to the 26-item Midlife Development Inventory to assess personality traits (openness, conscientiousness, extraversion, agreeableness and neuroticism), underwent cognitive testing in 2012/13 and 2015/16 and were followed for incidence of dementia (N=231) until 2019. RESULTS: Logistic regression, adjusted for sociodemographic factors, suggested a cross-sectional association with cognitive impairment for four of the five traits but only neuroticism was associated with incident cognitive impairment. All associations were completely attenuated when the analyses were adjusted for depression. Cox regression (mean follow-up: 6.18 years) adjusted for sociodemographic variables showed higher conscientiousness (HR per SD increment=0.72; 95% CI 0.65 to 0.81) and extraversion (HR=0.85; 95% CI 0.75 to 0.97) to be associated with lower dementia risk; higher neuroticism (HR=1.32; 95% CI 1.17 to 1.49) was associated with increased risk. Further adjustment for depression led to only conscientiousness retaining an association with dementia (HR=0.81; 95% CI 0.69 to 0.96), which was robust to adjustment for all covariates (HR=0.84; 95% CI 0.71 to 0.91; P=0.001). CONCLUSION: Our results show that only conscientiousness has an association with incidence of dementia that is not attributable to socioeconomic status or depression. The association of neuroticism with dementia was explained by depression.

Clinical features related to CSF level of amyloid Aß42 and Aß40 proteins in presence of lobar microbleeds.

In presence of lobar microbleeds, the exact clinical features related to the level of Aß42, Aß40 and to the Aß40/Aß42 ratio in the cerebrospinal fluid (CSF) are poorly known. We analyzed in 28 consecutive patients with such lesions, whose clinical or additional magnetic resonance imaging features are related to these biomarkers. The results showed that the presence of absence of hypertension, the extent or the antero-posterior distribution of white matter hyperintensities, the presence or absence of vascular lesions in the deepest parts of the brain, and the presence of dementia are related to variations of Aß42, Aß40 or of the Aß40/Aß42 ratio in the cerebrospinal fluid.

Epidemiology of neurological diseases in older adults.

Neurological diseases refer to the diseases that target the nervous system (brain, spine or nerves). They are the second leading cause of death, and the first cause of severe long-term disability in the world. The prevalence of most neurological diseases increases sharply with age, and age also modulates the impact of risk factors, clinical presentation and the natural course of these diseases. Longitudinal population-based studies provide useful insights for a better understanding of the specificities of neurological diseases in older adults by assessment of a wide range of risk factors. Rapid population aging, especially in low-income countries, presents challenges in terms of health and social care. A multidisciplinary approach is necessary to find solutions to tackle the burden of neurological diseases in older adults.

Diagnosis associated with Tau higher than 1200 pg/mL: Insights from the clinical and laboratory practice.

CONTEXT: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling. PATIENTS AND METHODS: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aß 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis. RESULTS: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aß1-42 and Aß1-42/pTau values differed significantly between the three groups of patients (p < .001). An Aß1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aß1-42 concentrations <550 pg/mL or pTau>60 pg/mL. CONCLUSION: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.

[Alzheimer's disease cerebro-spinal fluid biomarkers: A clinical research tool sometimes useful in daily clinical practice of memory clinics for the diagnosis of complex cases]. / Les biomarqueurs du liquide cérébro-spinal dans la maladie d'Alzheimer : un outil de recherche utile dans la pratique clinique courante des consultations mémoire pour les cas complexes.

The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aß1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aß1-40 amyloid peptide dosage helps to interpret Aß1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases.

PKR downregulation prevents neurodegeneration and ß-amyloid production in a thiamine-deficient model.

Brain thiamine homeostasis has an important role in energy metabolism and displays reduced activity in Alzheimer's disease (AD). Thiamine deficiency (TD) induces regionally specific neuronal death in the animal and human brains associated with a mild chronic impairment of oxidative metabolism. These features make the TD model amenable to investigate the cellular mechanisms of neurodegeneration. Once activated by various cellular stresses, including oxidative stress, PKR acts as a pro-apoptotic kinase and negatively controls the protein translation leading to an increase of BACE1 translation. In this study, we used a mouse TD model to assess the involvement of PKR in neuronal death and the molecular mechanisms of AD. Our results showed that the TD model activates the PKR-eIF2α pathway, increases the BACE1 expression levels of Aß in specific thalamus nuclei and induces motor deficits and neurodegeneration. These effects are reversed by PKR downregulation (using a specific inhibitor or in PKR knockout mice).

Relationship between blood pressure, cognitive function and education level in elderly patients with diabetes: a preliminary study.

AIMS: This study aimed to assess the relationship between blood pressure and cognitive function in elderly patients with diabetes mellitus (DM). METHODS: A total of 32 patients with DM aged ≥ 65 years (seven women and 25 men; mean ± SD age: 74.3 ± 6.4 years) were included in this cross-sectional study. Relationships between blood pressure and neuropsychological tests were determined using Spearman's rank correlations (ρ) and multivariable linear regression models. RESULTS: Lower diastolic blood pressure was associated with lower scores on the Frontal Assessment Battery (ρ=0.32, P=0.02), longer times to complete the Trail Making Test Part B (ρ=0.51, P=0.003), lower scores for the Finger Tapping Test (ρ=0.36, P=0.046) and less verbal fluency (ρ=0.36, P=0.047). In multivariable models, these relationships were attenuated after adjusting for levels of education. CONCLUSION: There was an association between lower diastolic blood pressure and poorer executive function in this cohort of elderly DM patients. These results underline the importance of systematic cognitive evaluation in elderly patients with DM, and suggest that a too-low diastolic blood pressure may have deleterious effects on mental function. Larger studies in the future are required to confirm these preliminary results.

Cognitive function after several years of antiretroviral therapy with stable central nervous system penetration score.

OBJECTIVES: Previous studies in HIV-infected populations have yielded conflicting results on the effect of antiretroviral therapy (ART) on cognition. Our objective was to investigate the effect of several years of ART with stable central nervous system penetration effectiveness (CPE) score on neuropsychological performance in HIV-infected individuals. METHODS: We analysed a clinical cohort of HIV-infected patients who initiated ART between June 2003 and December 2006 and maintained stable CPE scores. Patients were evaluated with a short neuropsychological battery. Using linear regression, we examined the relationship between results of cognitive tests and CPE scores in all patients. RESULTS: Patients were divided into three similarly sized groups (CPE ≤ 1, CPE between 1.5 and 2.5, and CPE ≥ 2.5). We found that ART with high CPE scores was associated with poorer executive performances in HIV-1-infected patients. CONCLUSION: These results suggest that cognitive performance in treated HIV-infected patients could be influenced by ART.

Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies.

Restless legs syndrome (RLS) often presents with paresthesias and dysesthesisas. We have investigated the prevalence and clinical features of RLS in a cohort of patients referred for clinical suspicion of peripheral neuropathy (PN). Sixty-four patients with sensory symptoms, and 101 age-matched controls were prospectively evaluated for RLS, PN and causes of both conditions. In the 64 patients (60 +/- 14 years), none were referred with a suspicion of RLS. Forty-one had a sensori-motor PN of which 22 had a definite RLS (54%). When excluding other causes of RLS, 8 of 41 patients had a RLS associated with a neuropathy (20%). The proportion of RLS in the healthy controls was 10%, lower than in the cohort of patients. In patients without PN, 57% had a RLS, and 55% in the whole cohort, a higher proportion than in the healthy controls (P < 0.0001). Patients with PN and RLS had more sleep disorders (P < 0.04), and legs and calves symptoms (P = 0.09) than patients with PN without RLS. Toes symptoms were more frequently observed in patients with PN but without RLS (P < 0.02). We conclude that RLS frequently presents with symptoms suggestive of peripheral neuropathy, and therefore, is often overlooked.

[Complete ophthalmoplegia complicating ophthalmic herpes zoster]. / Ophtalmoplégie complète compliquant un zona ophtalmique.

We report a case of a 73-year-old patient with complete ophthalmoplegia following an episode of ophthalmic herpes zoster. MRI showed an associated ipsilateral temporal meningioma with cavernous sinus extension. We discuss the possible responsibility of these two conditions in the ocular motor signs.

[Occlusion of the innominate artery in association with a primary antiphospholipid syndrome: treatment by angioplasty stenting]. / Occlusion du tronc artériel brachio-céphalique associée à un syndrome des antiphospholipides: traitement par angioplastie-stent.

INTRODUCTION: Antiphospholipid syndrome may be associated with stroke. CASE REPORT: We report a case of a symptomatic occlusion of the innominate artery in a 37-year-old patient, who developed primary anti-phospholipid syndrome. This association, to our knowledge, has not been reported in the literature. Occlusion of the innominate artery was treated by angioplasty-stenting. Effective oral anticoagulation was given to prevent a new thrombotic event. CONCLUSION: Systematic search for antiphospholipid antibodies is needed as part of the etiology work-up in young stroke victims.