Age-adjusted CSF t-tau and NfL do not improve diagnostic accuracy for prodromal Alzheimer's disease.

Cerebrospinal fluid total-tau (t-tau) and neurofilament light chain (NfL) are biomarkers of neurodegeneration and are increased in Alzheimer's disease (AD). In order to adjust for age-related increases in t-tau and NfL, cross-sectional age-adjusted norms were developed based on amyloid negative cognitively normal (CN) adults aged 41-78 years (CN, n = 137). The age-adjusted norms for t-tau and NfL did not improve receiver operating curve based diagnostic accuracies in individuals with mild cognitive impairment (MCI) due to AD (AD-MCI, n = 144).

Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.

Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status.

Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer's disease.

Background: Brain innate immune activation is associated with Alzheimer's disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles.

Regression-based normative data for the D-KEFS Color-Word Interference Test in Norwegian adults ages 20-85.

The Delis-Kaplan Executive Function System (D-KEFS) Color-Word-Interference Test (CWIT; AKA Stroop test) is a widely used measure of processing speed and executive function. While test materials and instructions have been translated to Norwegian, only American age-adjusted norms from D-KEFS are available in Norway. We here develop norms in a sample of 1011 Norwegians between 20 and 85 years.

Investigating the relationship between allocentric spatial working memory and biomarker status in preclinical and prodromal Alzheimer's disease.

The 4 Mountain Test (4MT) is a test of allocentric spatial working memory and has been proposed as an earlier marker of predementia Alzheimer's disease (AD) than episodic verbal memory. We here compare the 4MT to the CERAD word list memory recall in both cognitively normal (CN) and mild cognitive impairment (MCI) cases with or without cerebrospinal fluid markers (CSF) of Alzheimer's disease pathology. Linear regression was used to assess the influence of CSF determined Aβ-plaque (Aβ-/+) or neurofibrillary tau tangles (Tau-/+) on 4MT and CERAD recall performance.

Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden.

Importance: Identification of proteins and genetic factors that reduce Alzheimer disease (AD) pathology is of importance when searching for novel AD treatments. Heterozygosity of the KL-VS haplotype has been associated with reduced amyloid and tau burden. Whether this association is mediated by the Klotho protein remains unclear.

Stable cerebrospinal fluid neurogranin and β-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients.

Cerebrospinal fluid (CSF) β-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer's disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.

Regression-based cognitive change norms applied in biochemically defined predementia Alzheimer's disease.

Objective: We aim to develop 2-year cognitive change norms for adults ages 41-84 for six cognitive tests, and to evaluate these norms in groups with AD biomarkers.

Background: Practice effects are common in repeated neuropsychological testing. Not accounting for practice effects may obscure cognitive decline in early Alzheimer's disease (AD).

Reduction in manual asymmetry and decline in fine manual dexterity in right-handed older adults with mild cognitive impairment.

Research in Parkinson's or Alzheimer's disease suggests that hand function is affected by neurodegenerative diseases. However, little is known about the relationship between hand function and mild cognitive impairment (MCI). Therefore, we conducted a kinematic analysis of unimanual hand movements in MCI patients to answer whether manual asymmetries and manual dexterity are affected or preserved in this condition.

Regression-based normative data for the Rey Auditory Verbal Learning Test in Norwegian and Swedish adults aged 49-79 and comparison with published norms.

The Rey Auditory Verbal Learning Test (RAVLT) is a widely used measure of episodic verbal memory. To our knowledge, culturally adapted and demographically adjusted norms for the RAVLT are currently not available for Norwegian and Swedish adults, and imported North American norms are often used. We here develop regression-based norms for Norwegian and Swedish adults and compare our norms to North American norms in an independent sample of cognitively healthy adults.

Evaluation of Error Production in Animal Fluency and Its Relationship to Frontal Tracts in Normal Aging and Mild Alzheimer's Disease: A Combined LDA and Time-Course Analysis Investigation.

Semantic verbal fluency (VF), assessed by animal category, is a task widely used for early detection of dementia. A feature not regularly assessed is the occurrence of errors such as perseverations and intrusions. So far, no investigation has analyzed the how and when of error occurrence during semantic VF in aging populations, together with their possible neural correlates.

Assessing a Sensory-Motor-Cognition Triad in Amnestic Mild Cognitive Impairment With Dichotic Listening While Walking: A Dual-Task Paradigm.

A contemporary topic in aging research relates to the significance of cognitive changes proper to mild cognitive impairment (MCI) to higher risk of falls and gait deteriorations. The present study addresses this question in the amnestic type of MCI (aMCI) by examining a triad of interrelated comorbidities occurring in the MCI condition: attentional impairments, hearing loss and gait disturbances. To this end, we applied a dichotic listening (DL) test during over-ground walking.

Regression-based norms for the FAS phonemic fluency test for ages 40-84 based on a Norwegian sample.

The FAS phonemic fluency test is a commonly used neuropsychological test of executive function and processing speed. Although Norwegian discrete norms have been developed for the FAS test, American regression-based norms are frequently used by clinicians in Norway.However, language and cultural differences impact performance on the FAS test, and using foreign norms may not be appropriate.

Predictive and diagnostic utility of brief neuropsychological assessment in detecting Alzheimer's pathology and progression to dementia.

To assess the role of brief neuropsychological assessments in prediction and identification of Alzheimer's disease (AD) pathology and progression to AD dementia. Adults ( = 255; range = 40-81 years) with self-reported cognitive decline underwent baseline and 2-year follow-up clinical assessment, including a brief neuropsychological screening and lumbar puncture. Five different mild cognitive impairment (MCI) algorithms were applied on baseline cognitive test results: one conventional, three amnestic (lenient, stringent, multidomain), and one comprehensive criterion.

Demographically adjusted trail making test norms in a Scandinavian sample from 41 to 84 years.

Objective: The trail making test (TMT) is one of the most widely used neuropsychological tests. TMT-A provides measures of visual scanning/visuomotor speed and TMT-B involves additional demands on executive functions. Derived scores TMT B-A and TMT B/A enhance measures of executive functioning.

What does hand motor function tell us about our aging brain in association with WMH?

Background: White matter hyperintensities (WMH) are a common cerebral finding in older people. WMH are usually asymptomatic, but excessive WMH are associated with cognitive decline and dementia. WMH are also among the neurological findings most consistently associated with declining motor performance in healthy ageing.

The Role of Moderating Variables on BOLD fMRI Response During Semantic Verbal Fluency and Finger Tapping in Active and Educated Healthy Seniors.

Semantic verbal fluency is among the most employed tasks in cognitive aging research and substantial work is devoted to understanding the underlying mechanisms behind age-related differences at the neural and behavioral levels. The present investigation aimed to evaluate the role of moderating variables, such as age, sex, MMSE, and proxies of cognitive reserve (CR) on the hemodynamic response evoked by semantic verbal fluency in healthy young and healthy older adults. So far, no study has been conducted to this end.

Amyloid Plaques and Symptoms of Depression Links to Medical Help-Seeking due to Subjective Cognitive Decline.

Background: Subjective cognitive decline (SCD) is associated with an increased risk of Alzheimer's disease (AD). However, patients reporting SCD to their general practitioner are not always referred to a memory clinic.

Objective: To investigate whether prior history of medical help-seeking is associated with AD biomarker abnormality, worse cognitive performance, and/or depressive symptoms in SCD.

White matter correlates of gait perturbations resulting from spontaneous and lateralized attention in healthy older adults: A dual-task study.

To date the neural mechanisms behind gait perturbations caused by dual-task paradigms are still unknown. Therefore, the present study examined white matter correlates of gait perturbations caused by a dichotic listening task where spontaneous (free focus of attention) and lateralized attentional control (voluntary attention directed to right or left-ear) were tested. Fifty-nine right-handed, healthy older adults (59-88 years) were evaluated during single-task walking and three dual-task conditions.

Demographically adjusted CERAD wordlist test norms in a Norwegian sample from 40 to 80 years.

In recent years, several slightly younger cohorts have been established in order to study the preclinical and prodromal phases of dementia. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) wordlist memory test (WLT) is widely used in dementia research. However, culturally adapted and demographically adjusted test norms for younger ages are lacking.

Glial activation and inflammation along the Alzheimer's disease continuum.

Background: Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation.

Methods: We included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27).

In Brief Neuropsychological Assessment, Amnestic Mild Cognitive Impairment (MCI) Is associated with Cerebrospinal Fluid Biomarkers for Cognitive Decline in Contrast to the Prevailing NIA-AA MCI Criterion.

Background: In the care of persons with cognitive problems, it is important to use a valid mild cognitive impairment (MCI) criterion that discriminates well between normal and pathological aging.

Objective: To find the brief neuropsychological screening criterion that best correlates with cerebrospinal fluid (CSF) biomarkers for cognitive decline and dementia in persons seeking help for cognitive problems.

Methods: 452 consecutively recruited patients (age 40-80 years) from memory-clinics in the Norwegian national multicentre longitudinal study Dementia Disease Initiation were included.

Cerebrospinal fluid neurogranin/β-site APP-cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer's disease.

Introduction: The cerebrospinal fluid neurogranin (Ng)/β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) ratio may reflect synaptic affection resulting from reduced beta-amyloid (Aβ) clearance. We hypothesize that increased Ng/BACE1 ratio predicts the earliest cognitive decline in Alzheimer's disease.

Methods: We compared Ng/BACE1 levels between cases with subjective cognitive decline (n = 18) and mild cognitive impairment (n = 20) both with amyloid plaques and healthy controls (-ε4+, n = 16; -ε4-, n = 20).

Cortisol levels and cognitive profile in major depression: A comparison of currently and previously depressed patients.

The association between depressive symptoms and elevated cortisol levels, and depression and cognitive functioning, has been less robust in outpatients with symptoms in the mild to moderate range. Furthermore, the association between elevated cortisol levels and cognitive functioning is unclear. In the present study, currently depressed (n = 37), previously depressed (n = 81) and never depressed controls (n = 50) were assessed on a range of neuropsychological measures.