Biomedical subjects

Eric C Petrie

Publications and source records attributed to Eric C Petrie.

6 recordsLinked to original sources

PubMed2006

Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid.

BACKGROUND: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-beta (Abeta) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS). METHODS: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n=10) at 40 mg/day or pravastatin (a CNS impermeant statin; n=13) at 80 mg/day in hypercholesterolemic subjects without dementia. RESULTS: Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau181) in all subjects. There were no differences in CSF levels of total tau, Abeta42, Abeta40, soluble amyloid beta protein precursor (sAbetaPP) alpha or beta, or F2-isoprostanes. CONCLUSIONS: Statins may modulate the phosphorylation of tau in humans and this effect may depend on the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce the risk of AD.

Adult↗

PubMed2006

Lewy body pathology in late-onset familial Alzheimer's disease: a clinicopathological case series.

BACKGROUND: Lewy body pathology (LBP) is a common finding in Alzheimer's disease (AD), but the pathophysiology for this coexistent pathology remains unclear. METHODS: We ascertained late-onset dementia (mean age > 60 years old) families with at least 3 autopsies. We then conducted systematic alpha-synuclein (SNCA) immunostaining to determine the frequency and distribution of LBP in families with late-onset AD. RESULTS: All 32 subjects met NIA-Reagan neuropathological criteria for "high likelihood" of having AD. Hematoxylin and eosin staining detected LBP in the substantia nigra (SN) in 8 (25%) individuals. SNCA immunostaining detected LBP in 21 individuals (66%). While all subjects with SN LBP had co-existent amygdala LBP, many (9/21, 43%) of the cases with amygdala LBP did not have coexistent SN LBP (McNemar's chi-square test, p=0.008). Each family had at least two cases with LBP, but no family had LBP in all autopsied cases. CONCLUSIONS: Presence of significant AD pathology in one family member was highly predictive of similar pathology in other family members. However, despite the use of more sensitive SNCA immunohistochemistry, the presence of LBP was variable within all 7 families. Consistent with previous studies in sporadic and familial AD, the amygdala appeared to be the most vulnerable region for LBP in AD. Additional clinical, neuropathologic, and genetic studies are necessary to determine the clinical and pathological significance of LBP in AD.

Age of Onset↗

PubMed2005

Salivary cortisol and memory function in human aging.

OBJECTIVE: To examine the association of salivary cortisol with cognitive changes in a 3 year longitudinal study. Previous studies have suggested that elevated glucocorticoid concentrations alter hippocampal neuronal morphology, inhibit neurogenesis, and impair cognition. METHODS: Salivary cortisol samples were collected at home by 79 cognitively intact older persons (mean age 78+/-7 years) at 08:00, 15:00 and 23:00h, and collections were repeated annually for 3 years. Cognitive function was also assessed annually. RESULTS: The mean cortisol level of samples taken at three times of day and the cortisol concentration at 23:00h were significantly associated with poorer performance on tasks of declarative memory and executive function. Of 46 subjects who completed the entire 3 year study, higher initial cortisol concentration at 23:00h predicted a decline in performance of delayed paragraph recall. CONCLUSION: These results partially confirm previous findings that high cortisol is associated with impaired declarative memory function in non-demented older persons. In addition, our data show that high salivary cortisol concentrations predict a decline in memory function over the next 3 years.

Aged↗

PubMed2003

Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study.

OBJECTIVE: Prazosin is a centrally active alpha(1) adrenergic antagonist. The authors' goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans. METHOD: Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol. RESULTS: Prazosin (mean dose=9.5 mg/day at bedtime, SD=0.5) was superior to placebo for the three primary outcome measures: scores on the 1) recurrent distressing dreams item and the 2) difficulty falling/staying asleep item of the Clinician-Administered PTSD Scale and 3) change in overall PTSD severity and functional status according to the Clinical Global Impression of change. Total score and symptom cluster scores for reexperiencing, avoidance/numbing, and hyperarousal on the Clinician-Administered PTSD Scale also were significantly more improved in the prazosin condition, and prazosin was well tolerated. CONCLUSIONS: These data support the efficacy of prazosin for nightmares, sleep disturbance, and other PTSD symptoms.

Adrenergic alpha-Antagonists↗

PubMed2002

Neuroimaging in dementia with Lewy bodies: metabolism, neurochemistry, and morphology.

Dementia with Lewy bodies (DLB) is recognized as one of the most common forms of neurodegenerative dementia. Neuroimaging contributes to a better understanding of the pathophysiology of DLB by examining alterations in brain metabolism, neurochemisty, and morphology in living patients. Neuroimaging can provide objective and quantifiable antemortem markers for the presence of and the progression of DLB and permits differentiation from other dementias. This article reviews current neuroimaging findings in DLB with particular attention to occipital hypometabolism, dopaminergic and cholinergic deficits, and medial temporal lobe atrophy as measured by positron emission tomography, single-photon emission computed tomography, and magnetic resonance imaging.

Aged↗

PubMed2002

Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder.

BACKGROUND: Preclinical and clinical observations suggest that the centrally active alpha1-adrenergic antagonist prazosin might alleviate trauma content nightmares and other symptoms in combat veterans with chronic posttraumatic stress disorder (PTSD). METHOD: In this retrospective chart review study, we analyzed data from 59 consecutive combat veterans with previously treatment-resistant chronic PTSD (DSM-IV criteria) and severe intractable trauma content nightmares to whom prazosin had been prescribed. Nightmare severity was quantified using the recurrent distressing dreams item of the Clinician Administered PTSD Scale (CAPS). Change in overall PTSD severity exclusive of nightmares was estimated by assigning a Clinical Global Impressions-Change scale (CGI-C) score based on chart review. RESULTS: Mean +/- SEM recurrent distressing dreams item scores improved significantly (7.0 +/- 0.2 to 3.5 +/- 0.3, p <.0001) in the 36 patients who completed at least 8 weeks of prazosin treatment at their maximum titrated dose. The mean maximum prazosin dose achieved in these 36 patients was 9.6 +/- 0.9 mg/day. Recurrent distressing dreams scores also improved in the total group who filled their prazosin prescriptions (N = 51) (7.1 +/- 0.2 to 4.2 +/- 0.3, p <.0001). In a comparison group of 8 patients who did not fill their prazosin prescriptions but continued in outpatient treatment, there was no significant change in CAPS recurrent distressing dreams score (6.8 +/- 0.5 to 6.7 +/- 0.4). There also was at least some improvement in CGI-C ratings of overall PTSD severity exclusive of nightmares in a substantial majority of patients receiving prazosin, but not in the 8 comparison subjects. There were no serious adverse effects attributable to prazosin. CONCLUSION: These observations suggest that prazosin may relieve symptomatic distress in PTSD, and they provide rationale for placebo-controlled trials of prazosin for PTSD trauma content nightmares and other PTSD symptoms.

Adrenergic alpha-Antagonists↗