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PubMed2026

Plasma von Willebrand Factor and ADAMTS13 Interact With APOE-ε4 in Predicting Longitudinal Brain Atrophy and Cognitive Decline Over a 9-Year Follow-Up.

BACKGROUND: Von Willebrand factor (VWF) and ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) are linked to dementia risk, and limited evidence suggests apolipoprotein E (APOE)-ε4 alters VWF release. This study assessed whether baseline VWF and ADAMTS13 levels predict neurodegeneration and cognitive decline and evaluated effect modification by APOE-ε4 carriership. METHODS: Vanderbilt Memory and Aging Project cohort participants (n=332, 73±7 years, 59% male) completed serial blood draw, neuropsychological assessment, and brain magnetic resonance imaging over 6.4 years (range 1.4-9.7 years). Baseline plasma VWF and ADAMTS13 levels were quantified using mass spectrometry and Olink. Fully adjusted linear mixed-effects models related protein×time and protein×APOE-ε4×time interaction terms to longitudinal brain magnetic resonance imaging and neuropsychological outcomes. RESULTS: Lower baseline ADAMTS13 predicted faster declines in language (β=0.11, P=0.01), information processing speed (β=0.27, P=0.001), executive function (β=0.01, P=0.03), episodic memory (β=0.01, P=0.03), and visuospatial ability (β=0.11, P=0.001) and faster increases in global (β=-0.29, P=0.01) and frontal (β=-0.17, P=0.01) white matter hyperintensity volumes. Associations between ADAMTS13 and faster rates of cognitive decline and white matter injury were driven by APOE-ε4 carriers. Models relating VWF to longitudinal outcomes were null. APOE-ε4 interacted with VWF on longitudinal gray matter volumetric outcomes, such that faster rates of global gray matter atrophy were observed with higher baseline VWF levels among APOE-ε4 noncarriers only (β=-1530.5, P<0.001). CONCLUSIONS: ADAMTS13 shows promise as a potential plasma biomarker for brain aging outcomes, but additional research is warranted to understand the performance of VWF in the presence versus absence of an APOE-ε4 allele.

Humans↗

PubMed2024

Free-water: A promising structural biomarker for cognitive decline in aging and mild cognitive impairment.

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 ± 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 ± 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-ε4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (ΔRadj 2 = 3.47 ± 1.65%) and executive function (ΔRadj 2 = 2.43 ± 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (ΔRadj 2 = 8.13 ± 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

Alzheimer’s disease (AD)↗

PubMed1976

Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability.

Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups.

Antipsychotic Agents↗

PubMed1992

The effect of neuroleptics on cognitive and psychomotor function. A preliminary study in healthy volunteers.

The effects of haloperidol (1 mg), benzhexol (5 mg), diazepam (10 mg) and caffeine (400 mg) on subjective and objective measures of cognitive and psychomotor function were compared with placebo in 20 healthy volunteers. While both diazepam and benzhexol were associated with highly significant impairments in subjective altertness, critical flicker fusion threshold and choice reaction time (CRT), haloperidol could not be distinguished from placebo in most tests but was actually associated with an apparent improvement in CRT (in males) and simple visual reaction time. The perceptual maze test detected impairment by benzhexol on processing speed but was not sensitive to any other drug effects. Multiple-dose studies are required to establish if there is a true activating effect of haloperidol using a test of sustained attention. No effect of Eysenck personality subtype or life events on baseline or drug response data was detected.

Adult↗

PubMed1992

The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment in relation to progression of disease.

To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27 HIV negative, 193 HIV positive) completed tests evaluating premorbid intelligence, memory, non-verbal performance, information processing speed, and mood. When these measures were compared cross-sectionally by the severity of HIV illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two-choice decision time, delayed recall of the Wechsler Logical Memory Test and most components of the Auditory Verbal Learning Test. These findings imply reduced capacity for concentration, speed of thought and memory. When 101 patients were retested a mean of 16 months after their initial assessment, performance on Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory Test deteriorated more for patients at, or progressing within, CDC stage IV, than performance of patients at stage III. The results broadly correspond to the cross-sectional findings. However, there was a decline in all tests of memory function for the sample independent of clinical staging. This may be evidence of brain involvement before the appearance of other symptoms. Self-rated measures of mood did not change cross-sectionally, progressively, or interactively with time and stage of HIV illness, and cannot account for the changes in cognitive function observed. Change in drug use, similarly, does not account for the cognitive findings. Four (5%) of the retested subjects developed AIDS dementia complex, but most of the performance and memory impairments seen were subclinical despite the destructive neuropathology presumed to underlie intellectual decline in patients with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

PubMed1975

An electron microscopic study of the vascular factor in hemorrhagic diathesis.

Experimental diapedetic hemorrhage (oozing) was produced by streptokinase in rabbits and the fine structures of mesenterial microvessels were observed. Diapedesis of erythrocytes was seen in the venular side of microcirculation. On the contrary, no diapedesis was seen in true capillary on the arteriolar side. Sticking of erythrocytes to venular wall prior to diapedesis was proved, electron microscopically, to be the state in which red blood cells were trapped in the gaps on the endothelial junction. It was considered to be the morphological findings of the prediapedetic state. Erythrocytes passed through gaps on the endothelial junctions with high plasticities under any diapedetic conditions mentioned above. Furthermore, in author's experiments by ruthenium red staining, erythrocytes were observed just passing through the basement membrane under electron microscopy, in spite of its high speed process. It was found that the basement membrane is a very important barrier in erythrocyte diapedesis.

Animals↗

PubMed1976

A system for rapid analysis of long-term recordings of heart rate and other physiological parameters.

Using miniature cassette tape recorders, measurement of ECG and other physiological measures is possible in industrial or working situations. The development of a semi-automatic high speed processing system for analysis of the tape recorded data is described. This system decodes the signals on the tape, converts ECG to heart rate and presents a listing of the heart rate variation over the recording period, which may be up to 24 hours. A punched paper tape copy of the listing is used for input into a mainframe computer for subsequent analysis. The recorders and processing system have been used extensively for three years on a study of industrial work stress, and have proved reliable, accurate, and of sufficient sensitivity for in-depth analysis. They allow considerable data to be collected, permitting the thorough statistical analysis necessary for the interpretation of complex physiological responses.

Computers↗

PubMed1979

Speed of information processing in high and low susceptible subjects: a preliminary study.

Explore the source record for details and available documents.

Humans↗

PubMed1979

Processing determinants of reading speed.

Two groups of university undergraduates differing in reading ability were tested on a number of reaction-time tasks designed to determine the speed of encoding visual information at several different levels. In addition, the subjects were given tests of sensory functions, verbal and quantitative reasoning ability, short-term auditory memory span, and ability to comprehend spoken text. The groups did not differ on the sensory tests. However, the faster reader group had faster reaction times on all of the reaction-time tasks, and the size of the fast-reader advantage increased with the mean reaction time. Faster readers also performed more accurately in verbal and quantitative reasoning, short-term auditory memory, and speech comprehension. Regression analyses suggested that the ability to comprehend spoken material and speed of accessing overlearned memory codes for visually presented letters represented two important independent correlates of reading ability in our sample of subjects. Two variables reflecting these abilities--the percentage of correct answers to a listening comprehension test and the reaction time for correct responses in a letter-matching task--accounted for nearly all of the variance in reading ability tapped by both of our reading tests. In a second experiment, no reaction-time difference was found between fast and average readers in a matching task requiring no long-term memory code access but considerable visual information processing as indexed by overall mean reaction time. The results supported the conclusion that one skill allowing fast readers to capture more information from each reading fixation is faster access to letter codes from print.

Concept Formation↗

PubMed2022

Engineered helicase replaces thermocycler in DNA amplification while retaining desired PCR characteristics.

Polymerase Chain Reaction (PCR) is an essential method in molecular diagnostics and life sciences. PCR requires thermal cycling for heating the DNA for strand separation and cooling it for replication. The process uses a specialized hardware and exposes biomolecules to temperatures above 95 °C. Here, we engineer a PcrA M6 helicase with enhanced speed and processivity to replace the heating step by enzymatic DNA unwinding while retaining desired PCR characteristics. We name this isothermal amplification method SHARP (SSB-Helicase Assisted Rapid PCR) because it uses the engineered helicase and single-stranded DNA binding protein (SSB) in addition to standard PCR reagents. SHARP can generate amplicons with lengths of up to 6000 base pairs. SHARP can produce functional DNA, a plasmid that imparts cells with antibiotic resistance, and can amplify specific fragments from genomic DNA of human cells. We further use SHARP to assess the outcome of CRISPR-Cas9 editing at endogenous genomic sites.

Humans↗

PubMed1978

[Interhemispheric relations in the process of visual perception in schizophrenic patients].

The purpose of the performed study was to compare the time of visual stimuli perception for different hemispheres in normals and in schizophrenic patients. In normals there was a certain asymmetry in the speed of perception of letter stimuli between the right and left hemispheres. It was established, that in the right hemisphere there was a more rapid perception of the letters as compared to the left one. In schizophrenic patients there is no interhemispheric differences in the time of perception, owing to the fact that the right hemisphere loses the advantage in speed of processing visual information. The author makes an assumption of the possible role of disturbed activity of the right hemisphere in the psychopathological symptomatology.

Adolescent↗

PubMed1976

Comparison of nonretarded and mentally retarded children on a perceptual learning task.

The performances of 12 EMR and 12 nonretarded sixth-grade children on a perceptual learning task were compared to investigate the information processing of visually presented stimuli in individuals with different intelligence levels. A minicomputer flashed either familiar (lowercase) or unfamiliar letters (Gibson-like figures) in either a stimultaneous or successive mode on a same-different matching task. The computer automatically calculated accuracy and latency data for each subject. Results showed that accuracy was superior in the nonretarded group and that mean latencies for the EMR group was consistently higher than those of the nonretarded group. However, when latencies were corrected for differences in basic reaction time, there were no significant differences between the groups in the speed of processing the information.

Attention↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

PubMed1992

Intrinsic neuronal determinants of regeneration.

Axon growth and axon regeneration are co-operative processes; the speed and extent of axon growth are influenced both by the properties of the environment surrounding the axon growth cone, and the properties of the neuron itself. In recent years, the environmental influences on axon growth have received most of the attention directed towards this area of research, but the properties of the neurons themselves are likely to be just as important. Within both adults and embryos there are differences in the growth potential of different neuronal types, and there is also evidence for an overall decrease in the vigour of axon growth with neuronal age.

Animals↗

PubMed1975

Age differences in the speed of a spatial cognitive process.

Older subjects responded slower than younger subjects on a spatial task which required them to rotate mentally a perspectively drawn figure in order to judge whether it was congruent with a second figure. Decision time was partitioned into two components: (1) the time taken for the "mental rotation" process, (2) the time taken for the remaining processes such as stimulus encoding and motor output. Both components required more time in the elderly group. The increase with age in the component of decision time representing rotational processes was similar to those increases seen by other investigators examining age-dependent differences in time required for memory-scanning processes using verbal stimuli.

Adolescent↗

PubMed1992

Clinical measures to promote corneal epithelial healing.

It is necessary to know the specific pathobiology of a persistent epithelial defect to determine the strategy to be employed to assist in its repair. Lid position and function must be normal and any deficiency in the quantity and quality of the tears enhanced by tear preparations and closure of the lacrimal canaliculi. Adverse drug effects must be eliminated. Multiple corneal punctures and excision of reduplicated basal lamina have virtually eliminated the problem of recurrent corneal erosions. Control of any inflammatory process also speeds healing. Vitamin supplements, especially A, reverse defects associated with xerophthalmia. In any of these diseases, mechanical treatments consisting of soft contact lenses for persistent epithelial defects and collagen shields for the delivery of antibiotics or steroids to the eye may be employed. Tarsorrhaphy relieves the problem of persistent epithelial defects in neurotrophic keratitis and a variety of other conditions characterized by persistent surface breakdown. Preliminary data from open label studies of epidermal growth factors and fibronectin are encouraging but not yet conclusive.

Animals↗

PubMed1977

Neonatal records and the computer.

To use a combined single document clinical case sheet/computer record which can form the basic document for a life medical record is a practical proposition. With adequate briefing doctors and nurses soon become familiar with the record and appreciate its value. Secretarial and clerical requirements are reduced to a minimum as transcription of medical data is eliminated, so greatly speeding up processing and feed back to the medical services. A few illustrations of trends in neonatal statistics and of computer linked maternal/neonatal data are presented.

Computers↗

PubMed1979

Microsurgical lumbar discectomy: preliminary report of 83 consecutive cases.

The application of microsurgical technique to lumbar discectomy may be of dual value: minimal disruption of the integrity of normal anatomy and meticulous hemostasis may help to speed the process of convalescence, and the retention of epidural fat around the nerve root may help to prevent adhesions, a common cause of the late, "failed disc" syndrome. The authors report their experience with 83 consecutive microdiscectomies for lumbar disc protrusions. The results must be considered as tentative because the follow-up period has been short and the authors found it difficult to quantify the quality of health during the convalescent phase, although this seemed to be excellent. Their short term results are similar to those of the larger series reported by Williams, whose experience with microsurgical lumbar discectomies began 6 years ago. No other series have been reported. The authors describe their technique and compare it to that of Williams.

Adult↗