Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-β Protein Precursor β in the Subcortical Small Vessel Type of Dementia.

Background: The subcortical small vessel type of dementia (SSVD) is a common subtype of vascular dementia, but there is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers.

Objective: We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid-β protein precursor α (sAβPPα), sAβPPβ, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD), and mixed dementia (combined AD and SSVD).

Methods: This was a mono-center study of patients with SSVD (n = 38), AD (n = 121), mixed dementia (n = 62), and controls (n = 96).

Regional lithium prescription rates and recurrence in bipolar disorder.

Background: Lithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.

Aims: To estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.

Latent Cognitive Profiles Differ Between Incipient Alzheimer's Disease and Dementia with Subcortical Vascular Lesions in a Memory Clinic Population.

Background: It is unclear if latent cognitive profiles can distinguish between dementia with subcortical vascular lesions and Alzheimer's disease (AD) at the incipient stage, and if they differ in performance from the Petersen subtypes.

Objective: To identify latent cognitive profiles in a naturalistic population of patients from a memory clinic sample, and investigate the derived classes not only in terms of conversion to AD, but also in terms of conversion to dementia with subcortical vascular lesions. Another objective was to compare the derived classes to the Petersen subtypes.

Characteristic Biomarker and Cognitive Profile in Incipient Mixed Dementia.

Background: Research has shown that mixed dementia is more common than previously believed but little is known of its early stages.

Objective: To examine if incipient mixed dementia can be differentiated from incipient Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SVD) using neuropsychological tests, cerebrospinal fluid (CSF) markers, and magnetic resonance imaging markers.

Methods: We included 493 patients and controls from the Gothenburg MCI study and used the dementia groups for marker selection (CSF total-tau (T-tau), phospho-tau (P-tau), and amyloid-β42 (Aβ42), 11 neuropsychological tests, and 92 regional brain volumes) and to obtain cut-off values which were then applied to the MCI groups.

The five-items memory screen-extended variant: A tool for assessing memory.

Background And Purpose: The detection of memory impairment is an important part of dementia screening. However, the scope of memory measures in current screening batteries is limited. There is a need for a short yet sensitive instrument for early detection of memory impairment that could serve as a complement to existing globally oriented screening tests, for example, Mini-Mental State Examination (MMSE).

Better prognostic accuracy in younger mild cognitive impairment patients with more years of education.

Introduction: Age and years of education influence the risk of dementia and may impact the prognostic accuracy of mild cognitive impairment subtypes.

Methods: Memory clinic patients without dementia (N = 358, age 64.0 ± 7.

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.

Objective: Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects.

Similar pattern of atrophy in early- and late-onset Alzheimer's disease.

Introduction: Previous research on structural changes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have reported inconsistent findings.

Methods: In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer.

Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels.

Background/aims: The prognostic accuracy of mild cognitive impairment (MCI) in clinical settings is debated, variable across criteria, cut-offs, subtypes, and follow-up time. We aimed to estimate the prognostic accuracy of MCI and the MCI subtypes for dementia using three different cut-off levels.

Methods: Memory clinic patients were followed for 2 (n = 317, age 63.

Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.

Introduction: Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications.

Methods: Memory clinic patients ( = 235) were classified as SCD ( = 122): subtle cognitive decline ( = 36) and mild cognitive impairment ( = 77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3.

Cognitive reserve lessens the burden of white matter lesions on executive functions in bipolar disorder.

Background: The concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD.

Method: We tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75).

High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment.

Background/aims: Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimer's disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment).

Methods: Memory clinic patients (SCI: n = 90; age: 59.

Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls.

Introduction: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737.

Polymorphisms of dopamine pathway genes NRG1 and LMX1A are associated with cognitive performance in bipolar disorder.

Objectives: LIM homeobox transcription factor 1, alpha (LMX1A) and neuregulin 1 (NRG1) are susceptibility genes for schizophrenia that have been implicated in the dopaminergic pathway and have been associated with altered cognitive functioning. We hypothesized that single nucleotide polymorphisms (SNPs) in LMX1A and NRG1 would be associated with cognitive functioning in bipolar disorder.

Methods: In total, four SNPs were directly genotyped.

Alzheimer's disease--subcortical vascular disease spectrum in a hospital-based setting: Overview of results from the Gothenburg MCI and dementia studies.

The ability to discriminate between Alzheimer's disease (AD), subcortical vascular disease, and other cognitive disorders is crucial for diagnostic purposes and clinical trial outcomes. Patients with primarily subcortical vascular disease are unlikely to benefit from treatments targeting the AD pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment (MCI) and dementia studies are prospective, observational, single-center cohort studies suitable for both cross-sectional and longitudinal analysis that outline the cognitive profiles and biomarker characteristics of patients with AD, subcortical vascular disease, and other cognitive disorders.

The Gothenburg MCI study: Design and distribution of Alzheimer's disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up.

There is a need for increased nosological knowledge to enable rational trials in Alzheimer’s disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD.

CSF neuroinflammatory biomarkers in bipolar disorder are associated with cognitive impairment.

Persistent cognitive impairment in the euthymic state of bipolar disorder is increasingly recognized. Mounting evidence also suggests an association between neuroinflammation and cognitive dysfunction. The purpose of this study was to test if cerebrospinal fluid (CSF) markers of neuroinflammation could account for cognitive impairment in bipolar disorder.

Cognitive performance and cerebrospinal fluid biomarkers of neurodegeneration: a study of patients with bipolar disorder and healthy controls.

The purpose of the present study was to investigate if cerebrospinal fluid (CSF) biomarkers of neurodegeneration are associated with cognition in bipolar disorder and healthy controls, respectively. CSF concentrations of total and phosphorylated tau, amyloid beta (Aβ)1-42, ratios of Aβ42/40 and Aβ42/38, soluble amyloid precursor protein α and β, and neurofilament light chain protein were analyzed in relation to neuropsychological performance in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear regression models were applied to account for performance in five cognitive domains using the CSF biomarkers.

Differential Impact of Neurofilament Light Subunit on Cognition and Functional Outcome in Memory Clinic Patients with and without Vascular Burden.

The neurofilament light (NF-L) subunit is mainly expressed in large-caliber myelinated axons, and elevated concentrations in the cerebrospinal fluid (CSF) are correlated with damage to white matter and subcortical regions. Because the correlation between NF-L and cognition and functional impairment is largely unknown, we investigated associations in patients (n = 622) with (n = 199) and without (n = 423) vascular burden in subjective cognitive impairment (SCI, n = 168), mild cognitive impairment (MCI, n = 261), and dementia (n = 193). Patients were staged according to disease severity and the presence/absence of cerebrovascular disease.

Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates.

Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q)--a research tool discriminating between subjectively cognitively impaired patients and healthy controls.

Background: Subjective cognitive impairment (SCI) is a potential early marker for actual cognitive decline. The cognitive manifestation of the SCI stage is, however, largely unknown. Self-report instruments developed especially for use in the SCI population are lacking, and many SCI studies have not excluded mild cognitive impairment and dementia.

All cognitive systems but speed and visuospatial functions reduce the effect of CSF pathology on other systems.

The concept of reserve can be conceived as differences in the ability to compensate for pathology by recruiting additional or alternative networks. The purpose of this study was to examine whether certain cognitive systems may compensate for the effect of CSF amyloid beta 42 (Aβ42) and total tau (T-tau) on other cognitive systems. Five hundred and nine participants underwent neuropsychological examination and lumbar puncture.

Low cerebrospinal fluid sulfatide predicts progression of white matter lesions: The LADIS study.

Background/aims: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging.

Monte Carlo feature selection and rule-based models to predict Alzheimer's disease in mild cognitive impairment.

The objective of the present study was to evaluate a Monte Carlo feature selection (MCFS) and rough set Rosetta pipeline for generating rule-based models as a tool for comprehensive risk estimates for future Alzheimer's disease (AD) in individual patients with mild cognitive impairment (MCI). Risk estimates were generated on the basis of age, gender, Mini-Mental State Examination scores, apolipoprotein E (APOE) genotype and the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phospho-tau(181) (P-tau) and the 42 amino acid form of amyloid β (Aβ42) in two sets of longitudinally followed MCI patients (n = 217 in total). The predictive model was created in Rosetta, evaluated with the standard tenfold cross-validation approach and tested on an external set.

Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment.

Cerebrospinal fluid (CSF) measurements of amyloid-β42 (Aβ42), total-tau (T-tau), and phosphorylated tau (P-tau) may be used to predict future Alzheimer's disease (AD) dementia in patients with mild cognitive impairment (MCI). The precise temporal development of these biomarkers in relation to clinical progression is unclear. Earlier studies have been hampered by short follow-up.