Biomedical subjects

William Milberg

Publications and source records attributed to William Milberg.

10 recordsLinked to original sources

PubMed2024

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

BACKGROUND: Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. METHODS: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. RESULTS: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. CONCLUSION: The inclusion of exposure variables adds to the predictive power of MRS. Classification-based MRS may be useful in predicting risk of future PTSD in populations with anticipated trauma exposure. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting PTSD and, relatedly, improve their performance in independent cohorts.

Humans↗

PubMed2024

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

BACKGROUND: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. METHODS: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. RESULTS: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p-0.003), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. CONCLUSION: Results, especially those from the eMRS, reinforce earlier findings that methylation and trauma are interconnected and can be leveraged to increase the correct classification of those with vs. without PTSD. Moreover, our models can potentially be a valuable tool in predicting the future risk of developing PTSD. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting the condition and, relatedly, improve their performance in independent cohorts.

DNA methylation↗

PubMed2006

Cognitive dysfunction is associated with poor diabetes control in older adults.

OBJECTIVE: To evaluate the association between cognitive dysfunction and other barriers and glycemic control in older adults with diabetes. RESEARCH DESIGN AND METHODS: Patients over the age of 70 years presenting to a geriatric diabetes clinic were evaluated for barriers to successful diabetes management. Patients were screened for cognitive dysfunction with the Mini Mental State Examination (MMSE) and a clock-drawing test (CDT) scored by 1) a method validated by Mendez et al. and 2) a modified CDT (clock in a box [CIB]). Depression was evaluated with the Geriatric Depression Scale. Interview questionnaires surveyed activities of daily living (ADLs) and instrumental ADLs (IADLs), as well as other functional disabilities. RESULTS: Sixty patients (age 79 +/- 5 years, diabetes duration 14 +/- 13 years) were evaluated. Thirty-four percent of patients had low CIB (< or =5), and 38% of patients had low CDT (< or =13). Both CIB as well as CDT were inversely correlated with HbA(1c), suggesting that cognitive dysfunction is associated with poor glycemic control (r = -0.37, P < 0.004 and r = -0.38, P < 0.004, respectively). Thirty-three percent of patients had depressive symptoms with greater difficulty completing the tasks of the IADL survey (5.7 +/- 1.7 vs. 4.6 +/- 2.0; P < 0.03). These older adults with diabetes had a high incidence of functional disabilities, including hearing impairment (48%), vision impairment (53%), history of recent falls (33%), fear of falls (44%), and difficulty performing IADLs (39%). CONCLUSIONS: Older adults with diabetes have a high risk of undiagnosed cognitive dysfunction, depression, and functional disabilities. Cognitive dysfunction in this population is associated with poor diabetes control.

Aged↗

PubMed2005

Improvement of a face perception deficit via subsensory galvanic vestibular stimulation.

The remediative effect of galvanic vestibular stimulation (GVS) was investigated in a patient who, following right hemisphere damage, is profoundly unable to recognize faces. We administered a two-alternative forced choice match-to-sample task in which the patient had to choose which of two faces matched a sample face presented directly above, while bipolar, transcutaneous current was applied to the left and right vestibular nerves at a level below the patient's sensory threshold. Performance improved beyond the chance-level observed prestimulation, and relied on reversing the electrode polarity across two separate blocks of trials, such that each mastoid received positive current for one block and then negative charge for the next. Although our study involved only a single case, the data provide preliminary evidence that a deficit in perceptual face matching can be reduced by GVS. This raises the intriguing possibility that other unilateral visual disorders may also respond in such a manner.

Electric Stimulation Therapy↗

PubMed2005

Evidence for intact selective attention in Alzheimer's disease patients using a location priming task.

Researchers examining selective attentional mechanisms in patients with Alzheimer's disease (AD) often report impairment in patients' ability to inhibit irrelevant or distracting information. However, in many studies reporting such failures, researchers used tasks that require semantic processing, which a large body of literature documents to be disrupted in AD. The authors of this study used a spatial location-priming task that minimized semantic processing to examine the phenomena of negative priming and facilitative priming in 13 AD patients and 13 healthy older adults. AD patients demonstrated facilitative and negative priming proportionately equivalent to that of older adults. These findings suggest that both the facilitative and inhibitory mechanisms involved in selective attention are preserved in patients with AD and can be revealed in tasks that minimize semantic processing.

Aged↗

PubMed2004

Effect of blood pressure on cognitive functions in elderly persons.

BACKGROUND: Little is known about what specific cognitive functions are affected by elevated blood pressure (BP) and how orthostatic BP change is related to cognitive impairment. The aim of this study was to determine the effect of BP and its postural change on cognitive functions in otherwise healthy elders. METHODS: In 70 healthy persons (mean age, 72 +/- 4 years), supine systolic BP (SBP) was assessed 3 times using a sphygmomanometer, and the average values were obtained for the analysis. After 1, 3, and 5 minutes of standing, 3 BP measurements were obtained and the orthostatic SBP changes were determined by subtracting these values from the supine average. Neuropsychological tests were administered to assess short-term and long-term verbal and visual memory, visuospatial skills, and frontal-executive functions. Participants were considered impaired in the specific cognitive performance if their scores fell below the 25th percentile of the study population. Multiple logistic regression models were used to evaluate the relation of SBP and the magnitude of orthostatic SBP decline to risk for impairment in each of the cognitive tests. RESULTS: Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31-fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in psychomotor speed and set shifting as measured using the Trailmaking Part-B test. There was no significant association between cognitive functions and orthostatic SBP decline at 1, 3, and 5 minutes of standing. CONCLUSION: Elevation of BP is associated with a selective impairment in executive function in otherwise healthy community-dwelling elders.

Aged↗

PubMed2003

Summation priming in aphasia: evidence for alterations in semantic integration and activation.

The present study used a lexical decision paradigm to study the summation of priming effects in normal and aphasic participants. The amount of priming produced by pairs of definitionally converging associative words was compared to the amount of priming produced by pairs of single associative words and non-words in two experiments in which the ISI between primes and targets varied from 200 ms (Experiment 1) to 600 ms (Experiment 2). Control subjects showed a pattern of additive summation priming at the short ISI and overadditive summation priming at the longer ISI. Broca's aphasics showed overadditive priming at the short ISI and no significant priming at the longer ISI; Wernicke's aphasics showed no significant priming at the short ISI and additive priming at the longer ISI. These results suggest that aphasics differ from normals in their ability to integrate the activation derived from multiple linguistic associations and may provide an account of some of the clinical phenomenology of these patients.

Aged↗

PubMed2003

Taking the thumbs off the multidimensional scales in the debate on semantic memory and Alzheimer's disease: a comment on Storms et al. (2003).

G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) bring into focus at least 3 important issues. First, the performance of even simple tasks may be affected by several basic cognitive processes. Second, the statistical variance that these processes contribute to task performance may be different for a group of participants with neuropsychological deficits than for normal control particpants. Third, claims regarding the nature of semantic memory in Alzheimer's disease (AD) reflect indeterminacy about the nature and assessment of semantic memory itself. Critically, their analysis suggests that the T. Shallice and E. K. Warrington (1979) criteria widely used to operationalize the semantic memory deficit in AD be carefully scrutinized and reevaluated.

Alzheimer Disease↗

PubMed2002

Aware and unaware perception in hemispatial neglect: evidence from a stem completion priming task.

The current study used the process dissociation procedure in conjunction with a stem-completion priming task to disentangle the influences of aware and unaware perception in patients with hemispatial neglect. One lateralized picture prime was presented simultaneously with a filler picture followed by a centrally presented word stem. In the inclusion condition participants were asked to complete the word stem with the previously presented picture name; in the exclusion task they were asked to complete the stem with the name of a picture other than the one previously presented. Findings indicated that neglect patients had reduced unaware perception of pictures presented in the left visual field and an absence of awareness for those same pictures. In addition, patients had reduced awareness for right visual field pictures, but unaware perception remained intact. These findings suggest that observations of preserved information processing in neglect are due to residual unaware perception and not due to residual awareness of information in the neglected hemispace.

Aged↗

PubMed2002

Triangular backgrounds shift line bisection performance in hemispatial neglect: the critical point.

Isosceles triangular backgrounds influence line bisection performance in normal control participants and patients with hemispatial neglect. When the triangles are oriented asymmetrically with the vertex in I visual field, and the base in the other, the perceived midpoint of horizontal lines within the triangle is shifted towards the base, and away from the vertex. The current study examines this illusion further by systematically varying the extent of the triangle presented. With only fragments of the triangle in the background of the line, the vertex is the critical component driving the illusory shift in perceived midpoint. Patients with neglect and controls are equally sensitive to the illusion. Similar geometric illusions that are also intact in neglect, along with these results, suggest that preattentive, implicit visual processing is preserved in neglect and drives these illusions.

Aged↗