Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King’s College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

Peripheral compartments including blood and cerebrospinal fluid exhibit signals reflecting neuropathological changes in Alzheimer disease (AD).^1,2 In cerebrospinal fluid, these include a decrease in amyloid-β peptide (Aβ) and an increase in total and phosphorylated tau concentrations,³ reflecting amyloid sequestration as plaques and neurofibrillary degeneration, respectively.^4,5 Similarly, while numerous articles suggest that plasma concentrations of several metabolites and proteins might represent responses to neuropathological changes in AD,^6-11 these findings have not been conclusively replicated.¹² A limitation of such studies may be their reliance upon demonstrating changes between affected and unaffected people, a design of study that might identify secondary changes lacking relevance to core disease biology.

Introduction: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).Methods: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.Results: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R² = 0.10, test data set) and brain atrophy (R² ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.Discussion: Blood lipids are promising AD biomarkers that may lead to new treatment strategies.

As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests. Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data. 22 tests fitted criteria. Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good psychometric properties in primary care. In the secondary care settings, MMSE has considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT), Brief Alzheimer's Screen, HVLT, and 7 Minute Screen have good properties for detecting dementia but need further validation. Addenbrooke's Cognitive Examination (ACE) and Montreal Cognitive Assessment are effective to detect dementia with Parkinson's disease and Addenbrooke's Cognitive Examination-Revised (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests such as Test for Early Detection of Dementia, Test Your Memory, Cognitive Assessment Screening Test (CAST) and the recently developed ACE-III show promise but need validation in different settings, populations, and dementia subtypes. Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for dementia screening in acute hospital settings. Practitioners should use tests as appropriate to the setting and individual patient. More validation of available tests is needed rather than development of new ones.

Background: Neuropsychiatric symptoms (NPS) in dementia have received much attention due to their high prevalence and their significant implications. NPS in mild cognitive impairment (MCI), a clinical concept proposed as an intermediate state between normal aging and dementia, is now gradually gaining in interest. We aimed to conduct a selective review to examine the prevalence rate of NPS in MCI and associations of NPS symptoms with disease progression. Summary: We searched the PubMed database for articles on NPS in MCI and included articles that fulfilled the inclusion criteria. NPS was present in 35–85% of MCI patients. The most common symptoms were depression, irritability, apathy, anxiety, agitation, and sleep problems. Although the associated risk for disease progression of some symptoms, such as apathy and anxiety, was more consistent across studies, evidence was conflicting for symptoms like depression and sleep problems. NPS tend to co-occur, and certain combinations of NPS had a mutual or cumulative effect on disease progression. Late-onset NPS, even in a mild form (mild behavioural impairment) were found to be associated with an increased risk of dementia, even in the absence of cognitive impairment. Key Messages: NPS are highly prevalent in MCI patients and associated with subsequent cognitive deterioration. Late-onset NPS should raise suspicions of neurodegeneration. Future studies with improvised methodology are required to understand the interrelations of NPS and the role they play in the prognosis for patients with MCI.