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Biomedical subjects

L Volicer

Publications and source records attributed to L Volicer.

At least 19 recordsLinked to original sources
PubMed1999

PC12 cells transfected with a C-terminal fragment of the amyloid precursor protein (APP C-100), exhibit enhanced sensitivity to the calcium ionophore A23187, and diminished sensitivity to hydrogen peroxide.

Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is Abeta, a 39-43 amino acid peptide derived from the amyloid precursor protein (APP). APP C-100 is a C-terminal fragment of APP, 100 amino acids long, whose sequence includes Abeta. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H(2)O(2), rat PC12 cells were modified to overexpress APP C-100. Cellular survival (as measured in the MTT assay) was determined as a function of concentration for the calcium ionophore, A23187, and for H(2)O(2) in APP C-100 transfectants and vector-transfected controls. APP C-100 expression significantly increased cellular vulnerability to A23187, and decreased vulnerability to H(2)O(2).

Amyloid beta-Protein Precursor↗
PubMed1999

Enhanced inhibition of free radical-induced deoxyribose breakdown by Alzheimer brain homogenates.

The ability of homogenates from Alzheimer and control brains to inhibit formation of thiobarbituric acid reactive products (TBAR) induced by free radicals was compared. The assay for TBAR was modified by adding 1% sodium dodecyl sulfate (SDS) to prevent chromogen adsorption by biological matrices, and by extending the incubation time. The inhibitory activities required smaller equivalents of Alzheimer brain homogenates than control homogenates. Similar inhibitory activities were seen in homogenates from amygdala, temporal cortex and cerebellum. The inhibitory activities were similar in brain homogenates from individuals with different apolipoprotein E status. These results indicate that Alzheimer brain tissue has either increased content of free radical scavengers or is more sensitive to free radical attack than control brains.

Alzheimer Disease↗
PubMed1999

Development and testing of the Resistiveness to Care Scale.

A conceptual model and objective scale for measuring resistiveness to care in individuals with advanced dementia of the Alzheimer type (DAT) were empirically generated from the perspective of nursing staff caregivers and through observation of residents with DAT. The resistiveness to care scale (RTC-DAT) was judged to have content validity and reduced to 13 items. Quantifiable scoring procedures and methods for rating videotapes and conducting clinical observations were developed. The RTC-DAT was tested with 68 subjects at three sites. The RTC has a range of 0-156. Initial testing provided reliability estimates of .82-.87 for internal consistency and good to excellent kappas. Criterion-related validity with observed discomfort and construct validity by factor analysis support the RTC-DAT. Measurement issues and recommendations for use in research are discussed.

Activities of Daily Living↗
PubMed1999

Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia.

Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN), the putative site of the hypothalamic circadian pacemaker, to determine the nature and degree of pathologic changes caused by severe dementia. Neuropathologic examination indicated that among 30 patients with a clinical history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease, 3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had severe hippocampal sclerosis. Comparisons were made with a control group composed of 13 age-matched patients with no clinical or pathological evidence of dementia or other CNS disorders. To determine the pathologic involvement within the SCN, human hypothalami were stained with: Nissl, Bielchowsky silver, thioflavin S and specific antibodies directed against vasopressin (VP), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4) and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse plaques were noted. The pathologic changes within the SCN were less severe than in the other brain regions. Morphometric analysis was accomplished using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies provide evidence that both vasopressin and neurotensin neurons are lost in Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of disease-related pathology within the SCN. Taken collectively, our data support the hypothesis that damage to the SCN may be an underlying anatomical substrate for the clinically observed changes in circadian rhythmicity that have been observed in Alzheimer patients.

Case-Control Studies↗
PubMed1999

Evaluation of Simulated Presence: a personalized approach to enhance well-being in persons with Alzheimer's disease.

OBJECTIVE: To evaluate the efficacy of Simulated Presence, a personalized approach to enhance well-being among nursing home residents with Alzheimer's disease and related dementia's (ADRD). DESIGN: Latin-Square, double blinded, 3-factor design with restrictive randomization of three treatments (the study intervention, a placebo audio tape of a person reading the newspaper, and usual care). The three factors were treatment, time, and facility type. SETTING: Nine nursing homes in Eastern Massachusetts and Southern New Hampshire. PARTICIPANTS: Fifty-four subjects with documented ADRD who were aged 50 years or older, medically stable, had resided in their current nursing home for at least 3 months, and who had no planned discharge. All subjects had a history of agitated or withdrawn behaviors. INTERVENTION: The purpose of Simulated Presence is to provide a personalized intervention for persons with moderate to severe cognitive impairment. Through a unique testing process, some of the best loved memories of the ADRD person's lifetime are identified and then those memories are introduced to the patient in the format of a telephone conversation using a continuous play audio tape system. The intervention may be used for extended periods of time because each repetition is viewed as a fresh, live telephone call as a result of the short-term memory deficit of the person with ADRD. MEASUREMENTS: Direct observations of outcomes included using a newly developed scale, the Scale for the Observation of Agitation in Persons with Dementia, an agitation visual analog scale, the Positive Affect Rating Scale (mood and "interest"), a withdrawal visual analog scale, and facial diagrams of mood. Reported measures included daily staff observation logs of responses to interventions offered, and weekly staff surveys using the short-form Cohen-Mansfield Agitation Inventory and the Multidimensional Observation Scale for Elderly Subjects (mood and "interest"). Severity of dementia was assessed by the Mini-Mental State Exam, the Test for Severe Impairment, the Bedford Alzheimer's Nursing Scale, and the ADL Self-Performance Scale. RESULTS: Chi-square analysis of direct observations, using facial diagrams, revealed that Simulated Presence was equivalent to usual care (P = .141) and superior to placebo for producing a happy facial expression (P = .001). A positive effect was also documented in nursing staff observation logs using Analysis of Variance techniques (ANOVA) for subjects during Simulated Presence phases compared with the placebo phases (P < .001) and usual care phases (P < .001). According to ANOVA analyses of "interest" from weekly surveys, Simulated Presence was superior to both usual care (P = .001) and placebo (P = .008). We were unable to find evidence of significant differences (P < .05) among interventions for other direct observations and weekly reports of overall agitation or mood aspects of withdrawal. Subjects accepted the intervention most of the time, except for five subjects who refused it more than 50% of the time. CONCLUSION: This study provided evidence that Simulated Presence can be effective in enhancing well-being and decreasing problem behaviors in the nursing home setting as a substitute for or complement to usual care.

Aged↗
PubMed1997

Persistent vegetative state in Alzheimer disease. Does it exist?

OBJECTIVE: To determine if the published criteria for diagnosis of the persistent vegetative state could be applied to patients suffering from Alzheimer disease. DESIGN AND METHODS: Eighty-eight institutionalized patients with a diagnosis of possible or probable Alzheimer disease were evaluated for the presence of persistent vegetative state. Initial screening excluded patients who were able to do any of the following: feed themselves, respond to command, walk, or maintain continence of bowel and bladder. A sample of 12 of 28 patients unable to perform any of these functions was examined independently by 3 of us. RESULTS: During the first examination, 2 patients were diagnosed as being in a vegetative state by 2 of us and 3 additional patients by 1 of us. One of us did not diagnose any patient as being in a vegetative state. A second evaluation of the same patients was performed 2 months later, after holding a consensus meeting to standardize the evaluation procedure. During the second evaluation, the vegetative state was diagnosed in 6 patients but only by 1 of us. CONCLUSION: The diagnostic disagreement between the neurologists indicate that Alzheimer disease may only rarely progress to the persistent vegetative state.

Aged↗
PubMed1997

Postnatal changes of brain monoamine levels in prenatally malnourished and control rats.

The effects of age and prenatal protein malnutrition (6% casein diet) on the concentration of monoamine neurotransmitters and their metabolites and precursors in the hippocampal formation, striatum, brain stem and cerebral cortex were investigated in 1-, 15-, 30-, 45-, 90- and 220-day-old rats. Concentrations of all neurotransmitters, i.e. dopamine, norepinephrine and serotonin changed significantly during the development. However, two main patterns were recognized. Serotonin in all areas, and dopamine in the striatum, increased from birth to day 45, and declined significantly in 90-day-old rats. In contrast, norepinephrine in all areas, and dopamine in areas other than the striatum, showed the lowest levels in 30-day-old rats, with levels increasing gradually after this age. Concentrations of metabolites paralleled changes in corresponding neurotransmitter levels. Prenatal protein malnutrition did not significantly affect any neurotransmitter concentrations with the exception of increased tryptophan levels (181%) in the hippocampal formation of newborn rats and decreased tyrosine levels (59%) in the striatum of day 30 rats. The results indicate that the monoamine transmitter content varied dynamically throughout postnatal life; however, they seem to counteract the insult from prenatal protein malnutrition after postnatal nutritional rehabilitation.

Aging↗
PubMed1997

Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease.

A placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer's disease who were refusing food. Eleven patients completed both study periods; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis. The study was terminated in 3 patients: one developed a grand mal seizure and 2 developed serious intercurrent infections. Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.

Aged↗
PubMed1997

Physical status and complications in patients with Alzheimer disease: implications for outcome studies.

Physical illnesses commonly coexist with dementia of the Alzheimer type (DAT). Their presence complicates DAT research because it represents a confounding variable. Furthermore, some illnesses or their symptoms also may be used as outcome measures. The conditions that frequently occur in subjects with DAT include neurological complications, intercurrent infections, and malnutrition. This review summarizes data regarding the connections among these conditions and DAT.

Alzheimer Disease↗
PubMed1996

Neurotoxicity of free-radical-mediated serotonin neurotoxin in cultured embryonic chick brain neurons.

Exposure of serotonin (5-HT) to oxygen-derived free-radical-generating system, xanthine oxidase-hypoxanthine or to a Fenton reaction results in the formation of the neurotoxin, tryptamine-4,5-dione. In cultured embryonic chick brain neurons, incubation of tryptamine-4,5-dione or its ethyl carbonate derivative resulted in a dose-dependent neurotoxicity (1-100 microM). The addition of sulfhydryl compound, glutathione at 2 or 10 microM significantly enhanced the toxicity induced by 10 microM tryptamine-4,5-dione. On the contrary, glutathione at 10 microM decreased the neurotoxic effect caused by 10 microM 5,6- and 5,7-dihydroxytryptamine in the cultured neurons. The toxicity resulted from 5,6- and 5,7-dihydroxytryptamine could be fully prevented by a 5-HT uptake inhibitor, fluoxetine. However, the toxicity caused by tryptamine-4,5-dione and glutathione conjugate could not be blocked by fluoxetine (10 or 100 microM) or by a glutathione transferase inhibitor, boric acid/serine. The results indicate a different molecular mechanism among 5-HT derived neurotoxins and suggest that tryptamine-4,5-dione and/or its glutathione conjugate would cause neuronal damage, if they are formed in vivo.

5,6-Dihydroxytryptamine↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4.

Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one epsilon 4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking epsilon 4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband's APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility.

Adult↗
PubMed1996

Effect of fever-management strategy on the progression of dementia of the Alzheimer type.

This study was undertaken to determine if the progression of dementia of the Alzheimer type (DAT) is accelerated by an intercurrent infection and if management strategy (aggressive or palliative care) would modify this effect. A prospective cohort study compared the progression of DAT in patients in three 25-bed dementia special care units that provide a hospice option for care. There were three groups of patients, as follows: (a) developed a fever and received aggressive care (FAC, n = 30), (b) developed a fever and received palliative care (FPC, n = 19), and (c) did not develop a fever (NF, n = 46). The presence of a fever episode did not have an effect of its own on DAT progression. Over a 3-month period, DAT severity increased in most patients, but more so in FAC patients. Thus aggressive medical treatment of infections did not affect the underlying disease process and was associated with an acceleration of the progression of severity of DAT. Providing palliative care is recommended because it prevents patients from undergoing invasive diagnostic workups and treatments, does not accelerate the progression of DAT, and conserves scarce health care resources.

Activities of Daily Living↗
PubMed1995

Allele epsilon 4 of apolipoprotein E shows a dose effect on age at onset of Pick disease.

Pick disease is a rare progressive dementing illness characterized by severe atrophy of the frontal and temporal lobes. Clinically, Pick disease may be difficult to distinguish from Alzheimer disease (AD). The fact that Pick disease is often familial, and the evidence suggesting that the epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for AD and possibly other dementias, prompted us to study ApoE isoforms in Pick disease. ApoE genotypes were evaluated in an autopsy series of 21 AD and 12 Pick cases and compared with published data for a large group of adults participating in the Framingham Study. The distributions of ApoE genotypes in the AD and Pick patients and the controls were significantly different from one another. The frequency of epsilon 4 was 50.0, 20.0, and 13.6% in these respective groups. Linear regression analysis showed that the number of epsilon 4 alleles was inversely related to age at onset of Pick disease (P < 0.03) and accounted for 40% of the variation in age at onset. These results suggest that epsilon 4 may be a susceptibility factor for dementia and not specifically for AD. Experiments using a monoclonal antibody against ApoE suggest that neurons and Pick bodies are immunoreactive with ApoE. The dose effect of the epsilon 4 allele on age at onset of dementias other than AD and the association of ApoE immunoreactivity with neurons and Pick bodies support a broader role for ApoE in the pathogenesis of neuronal degeneration through interactions with the neuronal cytoskeleton.

Age of Onset↗
PubMed1995

Effect of prenatal malnutrition on release of monoamines from hippocampal slices.

The effect of prenatal protein malnutrition on release of monoamine neurotransmitters, their precursors and metabolites, from hippocampal slices was investigated in 15, 30, 90 and 220 days old male rats. The release of dopamine and its metabolites, tryptophan, and 5-hydroxyindoleacetic acid from hippocampal slices of malnourished rats was greater than release from control slices at all ages studied. Malnutrition also significantly increased the release of normetanephrine but only in the 220 day age group. Potassium-induced depolarization increased release of tyrosine, normetanephrine and 5-hydroxyindoleacetic acid less from slices of malnourished than from control rats. The release of norepinephrine, normetanephrine, serotonin and 5-hydroxyindoleacetic acid increased significantly with age while the release of tyrosine, 3,4-dihydroxyphenylacetic acid and homovanillic acid decreased significantly with age. Age was also significantly associated with the effectiveness of potassium-induced depolarization in increasing release of tyrosine, norepinephrine, normetanephrine, tryptophan, serotonin and 5-hydroxyindoleacetic acid.

Age Factors↗