Interest of biological biomarkers in the diagnostic approach of neurocognitive disorders in the elderly.

Alzheimer's disease (AD) is the most common cause of major neurocognitive disorders in older adults, affecting millions of individuals worldwide and leading to irreversible cognitive decline. The main neuropathological features of AD are brain amyloid deposition and neurofibrillary tangles. The biomarkers of AD are highly accurate in detecting these pathophysiological and neuropathological changes, up to several decades before the onset of cognitive impairment. They specifically reflect the presence of abnormal proteins in the brain, and can be measured reliably in the cerebrospinal fluid of affected individuals and in plasma for research purposes. Their implementation in clinical practice, together with neuropsychological assessment and neuroimaging, strongly increases diagnostic precision. Thus, amyloid and tau biomarkers can help rule out differential diagnoses such as vascular cognitive impairment or frontotemporal lobar degeneration. They also enable earlier diagnosis and are used in research to characterize the preclinical stage of AD. The new definition of AD has highlighted the usefulness of these biomarkers, shifting the focus from symptoms to biological and brain changes in living patients. Recent longitudinal studies demonstrated the ability of these biomarkers to predict future cognitive decline, regardless of the stage of the disease. Ongoing drug trials against AD systematically require diagnostic confirmation with biomarkers. Apart from clinical research, they have been increasingly used for several years in clinical practice, in secondary and tertiary-referral memory clinics. Nevertheless, their use has been raising ethical issues, in particular in the oldest old or in patients with multimorbidity. Their interpretation in patients older than 90 years is limited by the lack of evidence. The implications of a misdiagnosis of AD should be taken into account. Besides, there may be discrepancies between the biological diagnosis and the clinical course of the disease. In the absence of clear guidelines for their utilization, we hereby discuss their potential interests and limitations in older individuals.

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.