pituitrin and Alzheimer-Disease

The amygdala is a complex structure playing primary role in the processing and memorizing of emotional reactions. The amygdalae send impulses to the hypothalamus for activation of the sympathetic nervous system, to the reticular nucleus for increasing reflexes, to the nuclei of the trigeminal nerve and facial nerve for facial expressions of fear, and to the ventral tegmental area, locus coeruleus, and laterodorsal tegmental nucleus for activation of dopamine, norepinephrine and epinephrine release. The amygdala plays a key role in what has been called the "general-purpose defense response control network" and reacts in response to unpleasant sights, sensations, or smells. Anger, avoidance, and defensiveness are emotions activated largely by the amygdale. The amygdala is responsible for activating ancestral signs of distress such as "tense-mouth" and defensive postures such as crouching. Poor functioning of amygdala has also been associated with anxiety, autism, depression, narcolepsy, post-traumatic stress disorder, phobias, frontotemporal dementia, and schizophrenia. Impairment of emotional event memory in patients with Alzheimer's disease also correlates with the intensity of amygdalar damage. All these events speak out for the importance to preserve the normal function of the amygdala which can only be achieved by constant deepening of our knowledge about this unique structure.

Topics: Alzheimer Disease; Amygdala; Anxiety Disorders; Autistic Disorder; Corticotropin-Releasing Hormone; Dementia; Emotions; gamma-Aminobutyric Acid; Humans; Neurotransmitter Agents; Oxytocin; Schizophrenia; Vasopressins

Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.

Topics: Adult; Aged; Aging; Alzheimer Disease; Case-Control Studies; Circadian Rhythm; Cognition Disorders; Corticotropin-Releasing Hormone; Dehydroepiandrosterone; Dementia; Dementia, Vascular; Hippocampus; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Neuronal Plasticity; Pituitary-Adrenal System; Receptors, Steroid; Stress, Physiological; Vasopressins

The impact of ageing on the choroid plexus (CP)-CSF circulatory system has largely been un-investigated, or has been of interest only in relation to neurological disease. This paper reviews the evidence for age-related changes to the CP-CSF system and compares changes with disease states where appropriate. The changes discussed include reduced ion transport capabilities, evidence for oxidative stress, altered hormone interactions, decreased CSF secretion rates in animal models and the contradictory nature of human data, reduced clearance of protein from CSF, and slower fluid turnover. The potential impacts of these changes are highlighted, including the possibility of reduced resistance to stress insults and slow clearance of toxic compounds from CSF with specific reference to amyloid peptide. Other impacts may include the reduced ability of CSF to act as a circulating medium for hormone and growth factors to reach their brain targets, and reduced homeostasis of CSF nutrients (amino acids, vitamins), which might influence brain interstitial fluid homeostasis.

Topics: Aging; Alzheimer Disease; Animals; Cerebrospinal Fluid; Choroid Plexus; Energy Metabolism; Humans; Ion Transport; Oxidative Stress; Permeability; Vasopressins

Topics: Aging; Alzheimer Disease; Corticotropin-Releasing Hormone; Depression; Humans; Hypothalamus; Neuropeptides; Oxytocin; Vasopressins

Characteristic of the normal ageing process are changes in the renal, hormonal and thirst regulatory systems involved in the control of sodium and water balance. In the presence of disease or drug use, the ageing changes put the elderly person at increased risk of either sodium retention or loss and of water retention or loss. Clinically, these alterations in water and sodium balance are commonly expressed as either hyponatraemia or hypernatraemia with central nervous system dysfunction as the symptomatic expression. Thus, the impaired homeostasis of the many systems affecting fluid balance in the elderly is readily influenced by many of the disease states and medications which are often present in the elderly with resultant adverse clinical consequences. Awareness of these age-associated circumstances can allow the physician to anticipate the impact of illnesses and drugs and to implement a rational approach to therapeutic intervention and management.

Topics: Aged; Aging; Aldosterone; Alzheimer Disease; Atrial Natriuretic Factor; Humans; Kidney; Renin-Angiotensin System; Vasopressins; Water-Electrolyte Balance

Normal aging is accompanied by many changes in the hormonal systems involved in control of sodium and water balance. These alterations, together with age-associated changes in renal function, diminish the capacity of the elderly person to withstand the challenges of illness, drugs, and physiologic stresses. Thus, the aging individual is at increased risk of developing clinically significant alterations in sodium and water balance, which are commonly expressed as hyperatremia and hypoatremia. Awareness of the limitations of homeostatic ability allow the physician to anticipate the impact of illness and drugs on volume and electrolyte status and lead to prevention or to a rational approach to therapeutic intervention and management.

Topics: Aged; Aging; Aldosterone; Alzheimer Disease; Humans; Middle Aged; Renin-Angiotensin System; Sodium; Vasopressins; Water-Electrolyte Balance

Profound reductions in cortical acetylcholine levels together with degeneration of cholinergic neurons in the basal forebrain have been reported in patients with Alzheimer's disease. A similar loss of the cholinergic neurons of the basal forebrain and impairment of learning and memory occur in animals injected with a nerve growth factor-diphtheria toxin conjugate, suggesting that this animal model is suitable to analyze cholinergic roles on learning and memory processes, and also the pathogenesis of Alzheimer's disease. In addition, animal models constructed by electrolytic or neurotoxic lesioning of the basal magnocellular nucleus, and models made by transgenetic technology were described.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Disease Models, Animal; Memory; Nerve Growth Factors; Nerve Tissue Proteins; Neurons; Parasympathetic Nervous System; Prosencephalon; Vasopressins

Topics: Acetylcholine; Acetylcholinesterase; Adrenocorticotropic Hormone; Alzheimer Disease; Animals; Catecholamines; Cholinesterase Inhibitors; Endorphins; Humans; Memory; Neuropeptides; Neurotransmitter Agents; Serotonin; Vasopressins

The neuropeptide vasopressin (VP) is released from the neurohypophysis into the circulation where it acts as antidiuretic hormone on the kidney. In addition, VP is present in nerve cells and fibers in several areas in the rodent and primate brain where it acts as a neurotransmitter or neuromodulator. In the human brain a marked decrease in total cell number and VP cell number was observed in senescence in the suprachiasmatic nucleus, the hypothalamic nucleus regulating circadian rhythms. This degeneration was even more pronounced in Alzheimer's disease (AD) and might be related to the disturbances in sleep-wake cycle and endocrine rhythms which occur in this condition. No degenerative changes were observed with aging or in AD in the human hypothalamo-neurohypophyseal system (HNS); on the contrary, total cell numbers remain unaltered and the VP cells in this system are activated in senescence, probably in compensation for decreased sensitivity of the kidney to VP. It is proposed that this activation may prevent degeneration of the VP cells in the HNS. The extrahypothalamic VP innervation in the male rat brain was shown to be diminished in senescence in a number of areas. This innervation, which was previously shown to depend on plasma levels of sex-steroids, could be restored in a number of brain structures by subcutaneous testosterone administration to senescent male rats for one month. Reversibility of changes in VP innervation in the senescent rat brain through peripheral testosterone supplementation might open new possibilities for the development of therapeutic strategies in age-related disorders of the central nervous system.

Topics: Aging; Alzheimer Disease; Animals; Female; Male; Neurofibrils; Neurons; Neuropeptides; Rats; Rejuvenation; Testosterone; Vasopressins

Topics: Alzheimer Disease; Humans; Vasopressins

CSF neurotransmitter markers may reflect neurochemical alterations in Alzheimer's disease (AD). The best studied neurochemical deficit in AD is that of acetylcholine. Both acetylcholinesterase and butyrylcholinesterase activity have been reported to be reduced in some but not all studies of AD CSF. Studies of monoamine metabolites have also been controversial but most authors have found reduced concentrations of CSF HVA, lesser reductions in HIAA and no change in MHPG. CSF GABA concentrations have been found to be reduced in AD. Studies of CSF neuropeptides in AD have shown reduced concentrations of somatostatin and vasopressin, normal concentrations of vasoactive intestinal polypeptide and either normal or decreased concentrations of beta-endorphin and corticotropin releasing factor. Although no individual CSF neurochemical markers are specific for AD it may be possible to develop a profile of several neurochemical markers which will have enhanced specificity.

Topics: Alzheimer Disease; Biogenic Amines; Cholinesterases; gamma-Aminobutyric Acid; Humans; Neuropeptides; Neurotransmitter Agents; Somatostatin; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Animals; Cognition Disorders; Dementia; Humans; Neuropeptides; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Animals; Brain; Brain Chemistry; Humans; Memory; Neurons; Rats; Serotonin; Vasopressins

No class of presently available drugs is able to alleviate the cognitive deficits which accompany senile dementia. The present article critically reviews the strategies which have until now been used to treat these deficits. A description is given of the cognitive deficits which are commonly seen and of the cerebral substrate underlying memory processes. Furthermore, the various treatment strategies are critically reviewed as well as the rationale behind the use of the currently available drugs. It is concluded that no clinically significant improvement of cognitive disturbances can be obtained with the present available drugs. The neuropeptide strategy however may reveal new pharmacotherapeutic possibilities in the near future.

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Anticonvulsants; Brain; Catecholamines; Choline; Dementia; Dihydroergotoxine; Humans; Memory Disorders; Narcotic Antagonists; Nerve Tissue Proteins; Neuropsychology; Parasympatholytics; Phosphatidylcholines; Physostigmine; Piracetam; Trace Elements; Vasopressins; Vitamins

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Topics: Alzheimer Disease; Animals; Brain; Cholecystokinin; Choline O-Acetyltransferase; Endorphins; Epilepsy; Forecasting; Histocytochemistry; Humans; Huntington Disease; Migraine Disorders; Nerve Tissue Proteins; Nervous System Diseases; Pain; Parkinson Disease; Radioimmunoassay; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Tissue Distribution; Vasopressins

Many of the neurochemical changes associated with aging brain, particularly lower choline acetyltransferase and higher monoamine oxidase, occur with greater severity in senile dementia, Alzheimer's type (SDAT). These alterations correlate with neuropathologic indices, e.g., the number of senile plaques and tangles. Although many different treatment techniques have been used, most have been unsuccessful. No strong data have supported the use of stimulants, Gerovital H3, or hyperbaric oxygen. Among the vasodilators, cyclandelate and hydergine may be of value in some but not most patients. Much recent work has focused on techniques to increase acetylcholine brain concentrations. To date, precursors, such as choline, seem to have very limited value. Postsynaptic treatments, e.g., physostigmine, hold more hope for future benefit, if longer acting oral preparations are developed. Other compounds, such as ACTH, vasopressin, and piracetam, may have some value but need better definition and treatment indications. Recent discoveries on the influences of lecithin on membrane fluidity and receptor binding, may affect the focus of future pharmacologic investigation.

Topics: Adrenocorticotropic Hormone; Aged; Aging; Alzheimer Disease; Arecoline; Brain Chemistry; Choline; Cognition Disorders; Cyclandelate; Electroencephalography; Humans; Memory; Methylphenidate; Pentylenetetrazole; Phosphatidylcholines; Physostigmine; Piracetam; Procaine; Vasodilator Agents; Vasopressins

Topics: Aged; Alzheimer Disease; Animals; Brain; Cholecystokinin; Depressive Disorder; Endorphins; Female; Humans; Male; Mental Disorders; Middle Aged; Nerve Tissue Proteins; Neurotransmitter Agents; Schizophrenia; Substance P; Vasopressins

Topics: Alzheimer Disease; Amino Acid Sequence; Brain Injuries; Clinical Trials as Topic; Dementia; Humans; Memory; Memory Disorders; Middle Aged; Structure-Activity Relationship; Vasopressins

Topics: Alzheimer Disease; Humans; Vasopressins

Human motor activity has a robust, intrinsic fractal structure with similar patterns from minutes to hours. The fractal activity patterns appear to be physiologically important because the patterns persist under different environmental conditions but are significantly altered/reduced with aging and Alzheimer's disease (AD). Here, we report that dementia patients, known to have disrupted circadian rhythmicity, also have disrupted fractal activity patterns and that the disruption is more pronounced in patients with more amyloid plaques (a marker of AD severity). Moreover, the degree of fractal activity disruption is strongly associated with vasopressinergic and neurotensinergic neurons (two major circadian neurotransmitters) in postmortem suprachiasmatic nucleus (SCN), and can better predict changes of the two neurotransmitters than traditional circadian measures. These findings suggest that the SCN impacts human activity regulation at multiple time scales and that disrupted fractal activity may serve as a non-invasive biomarker of SCN neurodegeneration in dementia.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Biological Clocks; Biomarkers; Body Temperature; Circadian Rhythm; Dementia; Humans; Male; Middle Aged; Motor Activity; Neurons; Neurotensin; Neurotransmitter Agents; Suprachiasmatic Nucleus; Vasopressins

Circadian disturbances, including a fragmented sleep-wake pattern and sundowning, are commonly reported early in the progression of Alzheimer's disease (AD). These changes are distinctly different from those observed in non-pathological aging. Transgenic models of AD are a promising tool in understanding the underlying mechanisms and cause of disease. A novel triple-transgenic model of AD, 3xTg-AD, is the only model to exhibit both Abeta and tau pathology, and mimic human AD. The present study characterized changes pertaining to circadian rhythmicity that occur prior to and post-AD pathology. Both male and female 3xTg-AD mice demonstrated alterations to their circadian pacemaker with decreased nocturnal behavior when compared to controls. Specifically, males showed greater locomotor activity during the day and shorter freerunning periods prior to the onset of AD-pathology, and females had a decrease in activity levels during their typical active phase. Both sexes did not differ in terms of their freerunning periods or photic phase shifting ability. A decrease in vasoactive intestinal polypeptide-containing and vasopressin-containing cells was observed in the suprachiasmatic nucleus of 3xTg-AD mice relative to controls. This study demonstrates that abnormalities in circadian rhythmicity in 3xTg-AD mice precede expected AD pathology. This suggests that human studies may wish to determine if similar circadian dysfunction is predictive of early-onset AD.

Topics: Age Factors; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Analysis of Variance; Animals; Animals, Genetically Modified; Chronobiology Disorders; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Male; Mice; Mice, Inbred C57BL; Motor Activity; Nerve Growth Factors; Presenilin-1; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

The suprachiasmatic nuclei (SCN) are necessary and sufficient for the maintenance of circadian rhythms in primate and other mammalian species. The human dorsomedial SCN contains populations of non-species-specific vasopressin and species-specific neurotensin neurons. We made time-series recordings of core body temperature and locomotor activity in 19 elderly, male, end-stage dementia patients and 8 normal elderly controls. Following the death of the dementia patients, neuropathological diagnostic information and tissue samples from the hypothalamus were obtained. Hypothalamic tissue was also obtained from eight normal control cases that had not had activity or core temperature recordings previously. Core temperature was analysed for parametric, circadian features, and activity was analysed for non-parametric and parametric circadian features. These indices were then correlated with the degree of degeneration seen in the SCN (glia/neuron ratio) and neuronal counts from the dorsomedial SCN (vasopressin, neurotensin). Specific loss of SCN neurotensin neurons was associated with loss of activity and temperature amplitude without increase in activity fragmentation. Loss of SCN vasopressin neurons was associated with increased activity fragmentation but not loss of amplitude. Evidence for a circadian rhythm of vasopressinergic activity was seen in the dementia cases but no evidence was seen for a circadian rhythm in neurotensinergic activity. These results provide evidence that the SCN is necessary for the maintenance of the circadian rhythm in humans, information on the role of neuronal subpopulations in subserving this function and the utility of dementia in elaborating brain-behaviour relationships in the human.

Topics: Aged; Alzheimer Disease; Analysis of Variance; Body Temperature Regulation; Case-Control Studies; Cell Count; Circadian Rhythm; Humans; Immunohistochemistry; Male; Mediodorsal Thalamic Nucleus; Motor Activity; Neuroglia; Neurons; Neurotensin; Sleep; Vasopressins

The pineal hormone melatonin is involved in the regulation of circadian rhythms and feeds back to the central biological clock, the hypothalamic suprachiasmatic nucleus (SCN) via melatonin receptors. Supplementary melatonin is considered to be a potential treatment for aging and Alzheimer's disease (AD)-related circadian disorders. Here we investigated by immunocytochemistry the alterations of the MT1 melatonin receptor, the neuropeptides vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the SCN during aging and AD. We found that the number and density of AVP/VIP-expressing neurons in the SCN did not change, but the number and density of MT1-expressing neurons in the SCN were decreased in aged controls compared to young controls. Furthermore, both MT1-expressing neurons and AVP/VIP-expressing neurons were strongly diminished in the last neuropathological stages of AD (Braak stages V-VI), but not in the earliest stages (Braak stages I-II), compared to aged controls (Braak stage 0). Our study suggests that the MT1-mediated effects of melatonin on the SCN are disturbed during aging and even more so in late stage AD, which may contribute to the clinical circadian disorders and to the efficacy of therapeutic melatonin administration under these conditions.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Neurons; Postmortem Changes; Receptor, Melatonin, MT1; Statistics, Nonparametric; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

Topics: Alzheimer Disease; Amyloid Precursor Protein Secretases; Analgesics; Animals; Antidepressive Agents; Antipsychotic Agents; Aspartic Acid Endopeptidases; Drugs, Investigational; Hormone Antagonists; Humans; Neurosciences; Protease Inhibitors; Receptors, Metabotropic Glutamate; Vasopressins

We measured serum content of autoantibodies to beta-amyloid protein Abeta(1-42), its neurotoxic fragment Abeta(25-35), vasopressin, bradykinin, thrombin, antithrombin III, alpha(2)-macroglobulin, and angiotensin II in patients with various forms of Alzheimer's dementias, including presenile and senile dementias of the Alzheimer type. The ratio of antibradykinin and anti-Abeta(1-42) autoantibody contents differed by 39% in these patients. Our results can be used for the development of a new biochemical method for differential diagnostics of dementias of the Alzheimer type.

Topics: Aged; Aged, 80 and over; alpha-Macroglobulins; Alzheimer Disease; Amyloid beta-Peptides; Antithrombin III; Autoantibodies; Bradykinin; Humans; Middle Aged; Neurotoxins; Peptide Fragments; Peptides; Thrombin; Vasopressins

In various hypothalamic and adjacent brain regions we have previously found a remarkable increase in nuclear estrogen receptor staining in Alzheimer's disease (AD). In order to see whether this was a general phenomenon or rather specific for those areas that are affected by the AD process we investigated ERalpha and ERbeta expression in the arginine-vasopressin (AVP) neurons of the human dorsolateral suparoptic nucleus (dl-SON), that is the major source of plasma AVP. These neurons remain exceptionally intact in AD. Changes in ER expression were studied in relation to early Alzheimer changes (i.e. hyperphosphorylated tau) and neuronal metabolism in AD as determined by the size of the Golgi apparatus (GA) or cell size. No difference in neuronal metabolism (i.e. GA size or cell size) of AVP neurons was observed between AD and control patients and no early cytoskeletal AD alterations were found confirming the resistance of the dl-SON to AD. While no differences between AD and control patients were present for ERalpha and ERbeta staining except for a lower proportion of nuclear ERbeta AVP-positive neurons in AD subjects, complex sex differences not directly related to AD were observed within each group. The main finding of the present study is that in the dl-SON, that remains active and spared of AD changes, the increase in nuclear ERs seen in adjacent affected areas in AD patients does not occur. This indicates that a rise of nuclear ERs is not a generally occurring phenomenon but rather related to the pathogenetic alterations of the AD process.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cell Size; Cytoskeleton; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Golgi Apparatus; Humans; Immunohistochemistry; Male; Middle Aged; Neurons; Receptors, Estrogen; Supraoptic Nucleus; Tissue Fixation; Vasopressins

The paraventricular (PVN) and supraoptic nucleus (SON) demonstrate a striking stability with respect to cell numbers during aging and Alzheimer's disease (AD). Vasopressin (AVP) neurons even become activated during aging as judged from several parameters for neuronal activity, such as increased AVP plasma levels, enlarged nucleolar as well as cell size and an increased size of the Golgi apparatus in AVP-neurons. The activation possibly occurs as compensation for an age-related loss of AVP-receptors in the kidney. As a specific marker for AVP synthesis, we used quantitative in situ hybridization and estimated total amounts of AVP-mRNA in the entire SON and PVN of 14 control subjects and 14 AD patients that were matched for age, fixation time, postmortem delay and storage time of the tissue in paraffin. Following quantification, no differences were observed in total amounts of AVP-mRNA in the SON or PVN between young and old controls or between young and old AD patients, nor between the entire group of controls and AD patients. A significant negative correlation was found between the volume of the AVP-mRNA signal in the AD SON and age while the total amount of mRNA remained the same. This suggests a redistribution of cells or cell compartments in aging. A significant positive relation in both SON and PVN of AD patients was found between storage time of the paraffin-embedded tissue and the total amount of AVP-mRNA. A significant positive relation was present in the PVN, but not SON between pH of the cerebrospinal fluid, which is a marker for agonal state and the total amount of AVP mRNA. The present unchanged AVP-mRNA levels in SON and PVN confirm earlier observations on the stability of cell numbers in these nuclei in aging and AD. Although on the basis of other parameters, AVP-mRNA upregulation was expected, gradual, chronic stimulation over prolonged periods of time may, possibly, induce alternative mechanisms of regulation such as changes in translatability or in mRNA stability.

Topics: Adult; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Female; Humans; In Situ Hybridization; Male; Middle Aged; Paraventricular Hypothalamic Nucleus; Regression Analysis; RNA, Messenger; Supraoptic Nucleus; Vasopressins

The distribution of vasopressin and oxytocin immunoreactive fibers was examined in the pontine parabrachial nucleus of the human brain using purified polyclonal antibodies. The results revealed a striking predominance of vasopressin in this brain region. No obvious density difference, either in vasopressin or in oxytocin innervation, was found between Alzheimer's disease patients and matched controls. The present study corroborates other reports that suggest that in Alzheimer's disease the vasopressin innervation in the caudal part of the human brain is not affected.

Topics: Aged; Alzheimer Disease; Antibodies; Brain; Female; Humans; Immunohistochemistry; Male; Oxytocin; Pons; Tegmentum Mesencephali; Vasopressins

The vasopressin (VP) innervation of the human locus coeruleus (LC) was immunocytochemically investigated in Alzheimer's disease (AD) patients and non-demented controls. A dense innervation of VP fibers was present throughout the entire rostro-caudal length of the LC in both, controls and AD-patients. The VP immunoreactivity was confined to fibers; no signs of cell body staining could be found. Comparison of five non-demented control subjects and five AD patients on fifteen different levels throughout the LC revealed that the VP innervation of this nucleus remained intact in AD, even in the rostral part of the LC, which is the most affected region with respect to neuronal loss.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Female; Humans; Immunohistochemistry; Locus Coeruleus; Male; Nerve Degeneration; Nerve Fibers; Vasopressins

Individuals with Alzheimer's disease (AD) have been shown to have abnormalities in response to fluid restriction. Twelve subjects with AD and ten elderly controls underwent overnight fluid restriction followed by measurement of plasma and urine vasopressin and serum osmolality. Estimates of "thirst" were determined after one hour of ad libitum water intake. All subjects were tested with a Mini-Mental State Examination (MMSE) and Global Deterioration Scale (GDS). Individuals with AD had a greater degree of overnight dehydration than the elderly control group (serum osmolality 310 +/- 1 vs. 305 +/- 1 mosmol/kg, p = 0.02). There was no difference between the groups in the plasma or urinary levels of vasopressin. There was a direct correlation (r = 0.45, p = 0.03) of the amount of water intake as a measure of "thirst" with the MMSE score as a measure of cognitive functioning. Individuals with advanced cognitive impairment may be at risk of dehydration due to loss of protective "thirst" responses with secondary complications of dehydration.

Topics: Aged; Alzheimer Disease; Drinking Behavior; Female; Humans; Male; Middle Aged; Thirst; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Alzheimer's disease is a progressive deterioration of neuropsychological functioning. One of the main neuropathological correlates of the disease is a drop-out of cholinergic neurons within the central nervous system. The neuropeptide that is responsible for water homeostasis and defense against dehydration, vasopressin, is also under direct cholinergic control. Several studies have suggested that in Alzheimer's disease there has been a trend toward lower vasopressin levels than in age-matched controls. In order to improve discrimination of normal from diminished vasopressin levels, nine subjects with Alzheimer's disease (mean age 65 +/- 2 years) and nine age- and sex-matched controls (68 +/- 3 years) underwent a mild provocative challenge of overnight fluid restriction. Individuals with Alzheimer's disease had a greater degree of dehydration, with overnight serum osmolality of 313 +/- 4 vs 300 +/- 3 Mosmol/kg, P = .01, and diminished "thirst" as measured by water ingested in one hour of ad libitum water intake. Eight of the nine with Alzheimer's disease had levels of vasopressin which, by extrapolation, appear to be subnormal for their serum osmolalities, whereas seven of the nine control subjects has vasopressin levels within or above the reference range (P less than .05). Elderly individuals with Alzheimer's disease may be at increased risk of dehydration during periods of fluid restriction due to the loss of normal physiological responses of "thirst" and vasopressin secretion.

Topics: Aged; Alzheimer Disease; Cognition; Dehydration; Female; Humans; Male; Middle Aged; Osmolar Concentration; Sex Characteristics; Thirst; Vasopressins

As a first step toward assessing the status of brain neuropeptide systems that may be involved in Alzheimer's disease (AD), the cerebrospinal fluid (CSF) concentrations of the neuropeptides arginine vasopressin, somatostatin, oxytocin, and beta-endorphin were measured in patients with AD, normal elderly subjects, and normal young subjects. The plasma arginine vasopressin level was also measured in the three groups. The CSF arginine vasopressin level was significantly lower in patients with AD than in either elderly or young normal subjects, but oxytocin and beta-endorphin levels did not differ between groups. The CSF osmolarity also did not differ between groups. The plasma arginine vasopressin level did not significantly differ between groups, but high plasma arginine vasopressin values were absent in the patients with AD. The CSF somatostatin level was significantly lower in patients with AD than in normal elderly persons, but it did not differ in young normal subjects. These results suggest that central vasopressinergic activity may be decreased in AD and confirm reports of low CSF somatostatin levels in AD.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Arginine Vasopressin; beta-Endorphin; Endorphins; Female; Humans; Male; Osmolar Concentration; Oxytocin; Somatostatin; Vasopressins

Topics: Aging; Alzheimer Disease; Animals; Brain; Humans; Hypothalamus; Neurotransmitter Agents; Oxytocin; Paraventricular Hypothalamic Nucleus; Supraoptic Nucleus; Vasopressins

Vasopressin (VP) is involved as a neurotransmitter in a number of central functions that are frequently disturbed during aging and dementia. Therefore, this peptide has been used in clinical trials as a 'substitution therapy' for the degenerating peptidergic neurons, aimed at improving cognitive functions in aged and demented individuals with unequivocal results. In order to investigate whether the VP systems indeed show the claimed degenerative changes during aging and dementia, we focused in the first place on the Supra Optic Nucleus (SON) and Para Ventricular Nucleus (PVN). VP cells were identified by means of immunocytochemistry in a series of 32 formalin-fixed human hypothalami, including 4 patients with senile dementia of the Alzheimer type (SDAT). In the SON and PVN, VP cell and nucleolar size was determined by means of a digitizer device, as parameter for peptide synthesizing activity. VP cell size and nucleolar size increased beyond 80 years of age, both in the PVN and in the SON. In SDAT patients these measures fell within the range for their age group. Instead of degenerative changes, these results show an activation of the vasopressinergic system in senescence and in SDAT patients, similar to earlier observations in the aged rat and in accordance with a rise in human neurophysin and VP levels reported recently. The cause for these changes might be in the kidney. Immunocytochemical staining of VP binding sites in the renal tubuli was strongly diminished in kidneys of old (25 and 34 months) as compared to young (3 and 5 months) Wistar and Brown-Norway rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aging; Alzheimer Disease; Animals; Humans; Kidney; Middle Aged; Paraventricular Hypothalamic Nucleus; Rats; Receptors, Angiotensin; Receptors, Vasopressin; Supraoptic Nucleus; Vasopressins

The concentration of arginine vasopressin (AVP) was measured in cerebrospinal fluid (CSF) by radioimmunoassay. Serial dilution curves and reversed-phase high-pressure liquid chromatography (HPLC) showed that the material measured behaved identically to authentic vasopressin. Levels of CSF AVP were reduced by 37% in Alzheimer's disease, but were normal in Huntington's disease, normal-pressure hydrocephalus, and several other neurologic disorders. On direct comparison, the CSF AVP concentration was significantly lower in Alzheimer's disease than in normal-pressure hydrocephalus. Low CSF levels of AVP may therefore assist in the identification of demented patients who are not likely to benefit from ventricular shunting.

Topics: Aged; Alzheimer Disease; Humans; Middle Aged; Vasopressins