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Biomedical subjects

A Levey

Publications and source records attributed to A Levey.

13 recordsLinked to original sources
PubMed2004

Plasma testosterone levels in Alzheimer and Parkinson diseases.

BACKGROUND: Testosterone deficiency, a treatable condition commonly seen in aging men, has been linked to Parkinson disease (PD) and Alzheimer disease (AD). In normal subjects, low testosterone levels are associated with cognitive and neuropsychiatric symptoms, yet the relationship between testosterone levels and cognitive function in PD and AD remains unclear. OBJECTIVE: To examine the relationship of testosterone levels to age and cognitive function in PD and AD. METHODS: Plasma testosterone levels were determined in men enrolled in a clinical registry of subjects with PD and AD, and neuropsychological testing was performed on subjects who consented. Testosterone levels in men with PD were compared with those in men with AD. In both groups, the relationship between testosterone levels and neuropsychological test scores was analyzed, adjusting for age and education. RESULTS: Linear regression analysis revealed that testosterone levels decreased with age in male PD patients (p < 0.03) and male AD patients (p < 0.07). The rate of decline was similar for the two groups. In PD patients, lower testosterone levels were associated with poorer performance on Trails B Seconds (p < 0.02). CONCLUSIONS: There is a similar age-related decline in plasma testosterone levels in men with either PD or AD. Previously described associations between low testosterone levels and frontal lobe dysfunction in normal aged men, together with these results, suggest that the hormonal deficiency may act as a "second hit" to impair cognitive function in neurodegenerative disease.

Adult↗
PubMed2002

Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine.

Acetylcholinesterase is one of the most prominent constituents of central cholinergic pathways. It terminates the synaptic action of acetylcholine through hydrolysis and yields the choline moiety that is necessary for transmitter recycling. Despite these pivotal relationships, mice nullizygous for acetylcholinesterase established all principal anatomical components of central cholinergic pathways. No compensatory increase in the distribution of butyrylcholinesterase was detected. However, both the wild-type and nullizygous mice showed that butyrylcholinesterase enzyme activity extended to all parts of the brain receiving cholinergic innervation and that it could hydrolyze the acetylcholine surrogate acetylthiocholine. As opposed to acetylcholinesterase which was mostly of neuronal origin, butyrylcholinesterase appeared to be mostly of glial origin. These experiments lead to the unexpected conclusion that acetylcholinesterase is not necessary for the establishment of cholinergic pathways. They also show that butyrylcholinesterase can potentially substitute for acetylcholinesterase and that this enzyme is likely to play a constitutive (rather than just back-up) role in the hydrolysis of acetylcholine in the normal brain. The inhibition of butyrylcholinesterase may therefore provide a desirable feature of cholinergic therapies, including those aimed at treating Alzheimer's disease.

Acetylcholine↗
PubMed2001

Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models.

Movement, cognition, emotion, and positive reinforcement are influenced by mesostriatal, mesocortical, and mesolimbic dopamine systems. We describe a fourth major pathway originating from mesencephalic dopamine neurons: a mesothalamic system. The dopamine transporter, specific to dopamine containing axons, was histochemically visualized in thalamic motor and limbic-related nuclei and regions that modulate behavioral state as opposed to sensory nuclei in rats, nonhuman primates, and humans. Anatomical tracing established this innervation's origin via axon collaterals from the mesostriatal pathway. These findings implicate the thalamus as a novel site for disease specific alterations in dopamine neurotransmission, such as exist with nigral degeneration attending Parkinson's disease. This was confirmed in hemiparkinsonian animals where reduction of thalamic dopamine innervation occurred coincident with signs of active axonal degeneration. Individual mesencephalic dopamine neurons therefore have the potential to modulate normal and pathologic behavior not only through traditional nigrostriatal pathways but also by way of axon collaterals that innervate the thalamus.

Animals↗
PubMed2000

Subcellular localization of presenilins: association with a unique membrane pool in cultured cells.

We have investigated the subcellular distribution of presenilin-1 (PS1) and presenilin-2 (PS2) in a variety of mammalian cell lines. In Iodixanol-based density gradients, PS1 derivatives show a biphasic distribution, cofractionating with membranes containing ER-resident proteins and an additional population of membranes with low buoyant density that do not contain markers of the Golgi complex, ERGIC, COP II vesicles, ER exit compartment, COP II receptor, Golgi SNARE, trans-Golgi network, caveolar membranes, or endocytic vesicles. Confocal immunofluorescence and immunoelectron microscopy studies fully supported the fractionation studies. These data suggest that PS1 fragments accumulate in a unique subcompartment(s) of the ER or ER to Golgi trafficking intermediates. Interestingly, the FAD-linked PS1 variants show a marked redistribution toward the heavier region of the gradient. Finally, and in contrast to PS1, PS2 fragments are detected preponderantly in more densely sedimenting membranes, suggesting that the subcellular compartments in which these molecules accumulate are distinct.

Alzheimer Disease↗
PubMed1998

"U" curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc.

BACKGROUND: Hypertension may play an important role in the pathogenesis of the excess cardiovascular and cerebrovascular (CV) morbidity observed in hemodialysis patients (HD). However, the optimal blood pressure (BP) range for HD patients has not been defined. We postulated that there is a "U" curve relationship between BP and CV mortality. To explore this hypothesis we studied 5,433 HD patients in Dialysis Clinic Inc., a large not-for-profit chain, over a five year period. METHODS: Cox regression, with fixed and time-varying covariates, was used to assess the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP), pre- and post-dialysis, on CV mortality, while adjusting for age, gender, ethnicity, primary cause of end-stage renal disease, Kt/V, serum albumin, and antihypertensive medications. RESULTS: The overall impact of BP on CV mortality was modest. Pre-dialysis, neither systolic nor diastolic hypertension were associated with an increase in CV mortality. Post-dialysis, SBP > or = 180 mm Hg (RR = 1.96, P < 0.015) and DBP > or = 90 mm Hg (RR = 1.73, P < 0.05) were associated with increased CV mortality. Low SBP (SBP < 110 mm Hg) was associated with increased CV mortality, pre- and post-dialysis. CONCLUSIONS: The results suggest the presence of a "U" curve relationship between SBP post-dialysis and CV mortality in HD patients.

Adult↗
PubMed1994

The evaluative response: primitive but necessary.

We do not believe the claim that "evaluative conditioning is a qualitatively distinct form of classical conditioning" [Davey (1994). Behaviour Research and Therapy, 32, 291-299]. We view all classical conditioning as a learning process which leads organisms to assign a positive or negative value to previously neutral stimuli and to respond to them accordingly. The evaluative response is a necessary component of this process and hence it is central to all classical conditioning, not a separate type. Davey concentrates on a signal-based information processing view of learning, i.e. the formation of linear associations between CS and UCS of which human subjects are aware and which they can verbalize. We propose a more primitive and more general model in which stimulus evaluation (like/dislike) occurs with a minimal degree of processing, and enters into a representation of stimulus (CS and UCS) and response (CR and UCR) characteristics which is reintegrative rather than associative.

Animals↗