Endocannabinoid System Biomarkers in Alzheimer's Disease.

Alterations in the endocannabinoid system (ES) have been described in Alzheimer's disease (AD) pathophysiology. In the past years, multiple ES biomarkers have been developed, promising to advance our understanding of ES changes in AD. ES biomarkers, including positron emission tomography with cannabinoid receptors tracers and biofluid-based endocannabinoids, are associated with AD disease progression and pathological features.

Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline.

A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A) and tau PET-positive (T) in the medial temporal lobe (AT) and/or in the temporal neocortex (AT) and compared them with AT and AT groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the AT (hazard ratio (HR) = 19.

CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers.

Background: A putative role for iron in driving Alzheimer's disease (AD) progression is complicated by previously reported associations with neuroinflammation, apolipoprotein E and AD proteinopathy. To establish how iron interacts with clinicopathological features of AD and at what disease stage iron influences cognitive outcomes, we investigated the association of cerebrospinal fluid (CSF) biomarkers of iron (ferritin), inflammation (acute phase response proteins) and apolipoproteins with pathological biomarkers (CSF Aβ/t-tau, p-tau181), clinical staging and longitudinal cognitive deterioration in subjects from the BioFINDER cohort, with replication of key results in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

Methods: Ferritin, acute phase response proteins (n=9) and apolipoproteins (n=6) were measured in CSF samples from BioFINDER (n=1239; 4 years cognitive follow-up) participants stratified by cognitive status (cognitively unimpaired, mild cognitive impairment, AD) and for the presence of amyloid and tangle pathology using CSF Aβ/t-tau (A+) and p-tau181 (T+).

Striatal Hand Deformities in Parkinson's Disease: Hand Surgical Perspectives.

Background: The knowledge about striatal hand deformities (SHD) in Parkinson's disease (PD), has recently increased but need more attention due to their early impact on dexterity. The focus of clinical studies has been on the staging of SHD severity and neurological features. However, a hand surgical perspective has not been considered.

Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer's disease.

For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade of Aβ- and tau-related processes. Therefore, we set out to investigate how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer's disease (AD) continuum. Using human cross-sectional and longitudinal neuroimaging and cognitive assessment data, we show that in early stages of AD, increased concentration of soluble CSF p-tau is strongly associated with accumulation of insoluble tau aggregates across the brain, and CSF p-tau levels mediate the effect of Aβ on tau aggregation.

Functional connectivity in behavioral variant frontotemporal dementia.

Introduction: Functional connectivity (FC)-which reflects relationships between neural activity in different brain regions-has been used to explore the functional architecture of the brain in neurodegenerative disorders. Although an increasing number of studies have explored FC changes in behavioral variant frontotemporal dementia (bvFTD), there is no focused, in-depth review about FC in bvFTD.

Methods: Comprehensive literature search and narrative review to summarize the current field of FC in bvFTD.

Second-generation Elecsys cerebrospinal fluid immunoassays aid diagnosis of early Alzheimer's disease.

Objectives: Timely diagnosis of Alzheimer's disease (AD) is critical for appropriate treatment/patient management. Cerebrospinal fluid (CSF) biomarker analysis is often used to aid diagnosis. We assessed analytical performance of second-generation (Gen II) Elecsys CSF immunoassays (Roche Diagnostics International Ltd), and adjusted existing cut-offs, to evaluate their potential utility in clinical routine.

General anesthesia in early childhood and possible association with autism: a population-based matched cohort study.

Background: In experimental animal studies, exposure to general anesthesia in early childhood may results in changes in infant brain morphology and behavior, potentially leading to the development of autistic behaviors in the long-term. However, in clinical studies the role of exposure to general anesthesia in early childhood and the risk of autism is unknown.

Methods: This is a population-based cohort study including all children aged 0-5 years of age exposed to general anesthesia between 2001 and 2014 and a corresponding matched population without such an exposure.

Prevalence and Ascertainment of Dementia Cases in the Malmö Diet and Cancer Study.

Background: Register diagnoses, both hospital-based and from open clinic care, are often used in research studies in Sweden. The validity of such diagnoses has been debated and a validation assessment can improve the diagnostic accuracy for use in research studies.

Objective: The aim of this study was to investigate the quality of register-derived dementia diagnoses in the Malmö Diet and Cancer population study (MDCS) and to validate these diagnoses using systematic criteria.

Longitudinal Tau PET Using F-Flortaucipir: The Effect of Relative Cerebral Blood Flow on Quantitative and Semiquantitative Parameters.

Semiquantitative PET measures such as SUV ratio (SUVr) have several advantages over quantitative measures, such as practical applicability and relative computational simplicity. However, SUVr may potentially be affected by changes in blood flow, whereas quantitative measures such as nondisplaceable binding potential (BP) are not. For F-flortaucipir PET, the sensitivity of SUVr for changes in blood flow is currently unknown.

A Head-to-Head Comparison Between Plasma pTau181 and Tau PET Along the Alzheimer's Disease Continuum.

Both plasma tau phosphorylated at threonine-181 (pTau181) and tau PET show potential for detecting Alzheimer's disease (AD) pathology and predicting clinical progression. In this study, we performed a head-to-head comparison between plasma pTau181 and tau PET along the AD continuum. We included participants from the Amsterdam Dementia Cohort who underwent F-flortaucipir (tau) PET and had a plasma sample biobanked within 12 mo from tau PET.

Association Between Dietary Habits in Midlife With Dementia Incidence Over a 20-Year Period.

Background And Objectives: Dementia cases are expected to triple during the next 30 years, highlighting the importance of finding modifiable risk factors for dementia. The aim of this study was to investigate whether adherence to conventional dietary recommendations or to a modified Mediterranean diet are associated with a subsequent lower risk of developing all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), or with future accumulation of AD-related β-amyloid (Aβ) pathology.

Methods: Baseline examination in the prospective Swedish population-based Malmö Diet and Cancer Study took place in 1991-1996 with a follow-up for incident dementia until 2014.

Transversal functional connectivity and scene-specific processing in the human entorhinal-hippocampal circuitry.

Scene and object information reach the entorhinal-hippocampal circuitry in partly segregated cortical processing streams. Converging evidence suggests that such information-specific streams organize the cortical - entorhinal interaction and the circuitry's inner communication along the transversal axis of hippocampal subiculum and CA1. Here, we leveraged ultra-high field functional imaging and advance Maass et al.

High risk of developing dementia in Parkinson's disease: a Swedish registry-based study.

Dementia have substantial negative impact on the affected individual, their care partners and society. Persons living with Parkinson's disease (PwP) are also to a large extent living with dementia. The aim of this study is to estimate time to dementia in PD using data from a large quality register with access to baseline clinical and patient reported data merged with Swedish national health registries.

Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non-progressors.

Background: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative 'non-progressor' mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay.

Methods: Cerebrospinal fluid (CSF) NfL, amyloid beta 1-42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD.

Axonal degeneration and amyloid pathology predict cognitive decline beyond cortical atrophy.

Background: Cortical atrophy is associated with cognitive decline, but the association is not perfect. We aimed to identify factors explaining the discrepancy between the degree of cortical atrophy and cognitive decline in cognitively unimpaired elderly.

Methods: The discrepancy between atrophy and cognitive decline was measured using the residuals from a linear regression analysis between change in whole brain cortical thickness over time and change in a cognitive composite measure over time in 395 cognitively unimpaired participants from the Swedish BioFINDER study.

Corrigendum to "Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer's disease" [Clin. Mass Spectrom. 14 (Part B) (2019) 74-82].

[This corrects the article DOI: 10.1016/j.clinms.

Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer's disease.

Background: In Alzheimer's disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels-which differ substantially between white matter tracts in the brain-are a key modulating factor of region-specific susceptibility to tau deposition.

Confounding factors of Alzheimer's disease plasma biomarkers and their impact on clinical performance.

Introduction: Plasma biomarkers will likely revolutionize the diagnostic work-up of Alzheimer's disease (AD) globally. Before widespread use, we need to determine if confounding factors affect the levels of these biomarkers, and their clinical utility.

Methods: Participants with plasma and CSF biomarkers, creatinine, body mass index (BMI), and medical history data were included (BioFINDER-1: n = 748, BioFINDER-2: n = 421).

Clinical performance and robustness evaluation of plasma amyloid-β prescreening.

Introduction: Further evidence is needed to support the use of plasma amyloid β (Aβ) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma Aβ /Aβ for amyloid positivity prescreening.

Methods: Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants.

Measures of cortical microstructure are linked to amyloid pathology in Alzheimer's disease.

Markers of downstream events are a key component of clinical trials of disease-modifying therapies for Alzheimer's disease. Morphological metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect amyloid-beta (Aβ)- related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes and to test their associations with multiple aspects of the Alzheimer's disease pathological cascade, including both Aβ and tau accumulation, astrocytic activation and cognitive deficits.