pituitrin and Dementia

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

Vasopressin (VP) is distributed in many parts of the brain. VP regulates the hypothalamo-pituitary-adrenal axis together with the corticotropin-releasing hormone. It closely follows a 24-h rhythm in the suprachiasmatic nucleus (SCN) and influences memory and behavior in the septum. clinical evidence suggests that VP might be related to depression and dementia. In this review, the central distribution of VP-containing cells, the physiological action of VP and related findings in depressed patients and demented patients are described.

Topics: Adrenocorticotropic Hormone; Animals; Brain; Dementia; Depression; Humans; Hypothalamo-Hypophyseal System; Paraventricular Hypothalamic Nucleus; Pituitary Gland, Anterior; Pituitary-Adrenal System; Receptors, Vasopressin; Stress, Physiological; Supraoptic Nucleus; Vasopressins

Topics: Age Factors; Aged; Anticoagulants; Antioxidants; Brain; Calcium Channel Blockers; Dementia; Humans; Neurotransmitter Agents; Platelet Aggregation Inhibitors; Somatostatin; Vasodilator Agents; Vasopressins

Topics: Animals; Dementia; Humans; Protein Biosynthesis; RNA; Vasodilator Agents; Vasopressins

The authors discuss cerebral vasodilators, cerebral metabolic enhancers, nootropics, opioid antagonists, psychostimulants, cholinergic agents, and neuropeptides. Their efficacy in the treatment of dementing illnesses is evaluated.

Topics: 4-Aminopyridine; Acetylcholine; Adenosine Triphosphate; Aged; Aminopyridines; Central Nervous System Stimulants; Cerebrovascular Circulation; Clinical Trials as Topic; Dementia; Double-Blind Method; Humans; Levodopa; Nafronyl; Narcotic Antagonists; Nerve Tissue Proteins; Parasympathomimetics; Pentylenetetrazole; Physostigmine; Piracetam; Procainamide; Vasodilator Agents; Vasopressins

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

The authors discuss cerebral vasodilators, cerebral metabolic enhancers, nootropics, opioid antagonists, psychostimulants, cholinergic agents, and neuropeptides. Their efficacy in the treatment of dementing illnesses is evaluated.

Topics: 4-Aminopyridine; Acetylcholine; Adenosine Triphosphate; Aged; Aminopyridines; Central Nervous System Stimulants; Cerebrovascular Circulation; Clinical Trials as Topic; Dementia; Double-Blind Method; Humans; Levodopa; Nafronyl; Narcotic Antagonists; Nerve Tissue Proteins; Parasympathomimetics; Pentylenetetrazole; Physostigmine; Piracetam; Procainamide; Vasodilator Agents; Vasopressins

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

Since the description of its antidiuretic effect in 1913, a variety of functions have been attributed to vasopressin, one of the most controversial throughout the years probably being its effect on memory processes. In an attempt to study the actual secretory rhythm of vasopressin in humans with demonstrated impaired memory, the plasma and cerebrospinal fluid levels of the peptide have been examined during 24 h in a group of patients with dementia, and their values compared with two healthy control groups of young and elderly volunteers. Patients with dementia had higher circulating levels of vasopressin in plasma than the healthy participants and the differences were statistically significant when compared with the healthy elderly (p = 0.003). This difference is not age-related because both groups were in the same age range. A possible explanation could be the higher plasma osmolality measured in the patients with dementia, despite the fact that their levels were within the normal ranges. The different results could not be attributed to changes in electrolytes or blood pressure because these parameters were similar in all groups (p = NS). But more interesting, perhaps, is the secretory pattern found in all three groups. The pattern is biphasic, with two significant peaks: at 16.00 h (p = 0.032) and at night (p = 0.002). This pattern was similar in all cases and in all groups. The total nocturnal secretion of vasopressin is higher than the diurnal secretion (p = 0.02) only in the plasma because the cerebrospinal fluid values were higher during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Aging; Circadian Rhythm; Dementia; Electrolytes; Female; Humans; Male; Middle Aged; Osmolar Concentration; Vasopressins

Topics: Adult; Aged; Aged, 80 and over; Animals; Dementia; Dystonia; Female; Humans; Male; Middle Aged; Movement Disorders; Sincalide; Vasopressins

Topics: Adult; Aged; Aging; Brain; Dementia; Female; Humans; Male; Middle Aged; Neurons; Vasopressins

In 16 patients with primary degenerative dementia mean CSF vasopressin concentration was lower (0.9 +/- 0.1 pg/ml (mean +/- SEM)) than in 28 control patients (1.3 +/- 0.1 (mean +/- SEM)) (p less than 0.01). In 18 patients with normal pressure hydrocephalus and potentially reversible dementia mean CSF vasopressin concentration (1.2 pg/ml +/- 0.1 (mean +/- SEM)) was not different from that found in controls. Several of the demented patients had inappropriate plasma vasopressin concentrations suggesting a defect in osmoregulation. These findings encourage further clinical trials of vasopressin in patients with primary degenerative dementia, but it is emphasised that the low CSF vasopressin concentration in these patients might be only a nonspecific phenomenon due to the diffuse loss of cells within the central nervous system.

Topics: Adult; Aged; Dementia; Female; Humans; Hydrocephalus; Hydrocephalus, Normal Pressure; Male; Middle Aged; Vasopressins

Thyrotrophin-releasing hormone and gonadotrophin-releasing hormone were measured in lumbar CSF from patients with idiopathic senile dementia, cerebral tumours and spinal disc lesions. Somatostatin was also measured in lumbar CSF from patients with dementia and patients with other neurological disorders, but the numbers involved were much smaller. The levels of these neuropeptides were significantly reduced in the patients with senile dementia. These results suggest a possible involvement of hpothalamic neuropeptides in idiopathic senile dementia.

Topics: Aged; Brain Neoplasms; Dementia; Gonadotropin-Releasing Hormone; Humans; Intervertebral Disc Displacement; Nervous System Diseases; Somatostatin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Aged; Aging; Cyclic AMP; Cyclic GMP; Dementia; Female; Humans; Male; Middle Aged; Vasopressins

Topics: Adult; Dementia; Female; Humans; Male; Middle Aged; Psychoses, Substance-Induced; Vasopressins; Water Intoxication

Topics: Brain Neoplasms; Carcinoma, Bronchogenic; Cerebral Cortex; Dementia; Glioma; Humans; Hyponatremia; Liver Neoplasms; Lymph Nodes; Male; Mental Disorders; Middle Aged; Neoplasm Metastasis; Seizures; Sodium; Thalamus; Vasopressins