Current treatments for sleep disturbances in individuals with dementia.

Sleep disturbances are widespread among older adults. Degenerative neurologic disorders that cause dementia, such as Alzheimer's disease and Parkinson's disease, exacerbate age-related changes in sleep, as do many common comorbid medical and psychiatric conditions. Medications used to treat chronic illness and insomnia have many side effects that can further disrupt sleep and place patients at risk for injury. This article reviews the neurophysiology of sleep in normal aging and sleep changes associated with common dementia subtypes and comorbid conditions. Current pharmacologic and nonpharmacologic evidence-based treatment options are discussed, including the use of light therapy, increased physical and social activity, and multicomponent cognitive-behavioral interventions for improving sleep in institutionalized and community-dwelling adults with dementia.

[Effects of gypsum on the firing of pyrogen-treated thermosensitive neurons in PO/AH of cats].

AIM: To investigate the possible central mechanism of antipyretic effects of Chinese medicine gypsum. METHODS: Gypsum was injected after the fever model was established. The firing rate of thermosensitive neurons in preoptic-anterior hypothalamus(PO/AH) region was recorded by using extracellular microelectrode technique. RESULTS: The injection of pyrogen evoked decrease in firing rate of the warm-sensitive neurons and increase in the cold-sensitive neurons in the region of PO/AH; the changes of the firing rate of pyrogen- treated warm-sensitive and cold-sensitive neurons could be reversed by the injection of gypsum. CONCLUSION: The result may suggest that antipyretic action of gypsum is mediated by its influences on the thermosensitivity neurons in the region of PO/AH.

Diminished alpha 2-adrenoceptor-mediated modulation of noradrenergic neurotransmission in the posterior hypothalamus of spontaneously hypertensive rats.

An azepine derivative, 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine (B-HT 920; 100 nM), inhibited the evoked noradrenaline release from slices of rat posterior hypothalamus, and yohimbine (100 nM) potentiated the release from slices of rat anterior and posterior hypothalamus. In the posterior hypothalamus of 4- and 15-16-week-old spontaneously hypertensive rats (SHRs), as compared with age-matched Wistar-Kyoto rats (WKYs), the inhibitory effect of B-HT 920 and the facilitatory effect of yohimbine were decreased. In the anterior hypothalamus there was no significant difference in the yohimbine effect between WKYs and SHRs, at either age. It is concluded that alpha 2-adrenoceptor-mediated autoinhibition of noradrenergic neurotransmission is diminished in the posterior hypothalamus of SHRs.

[Reactions of the neurons of various hypothalamic structures to tooth pulp and sciatic nerve A beta-fiber stimulation in the cat]. / Reaktsii neironov razlichnykh struktur gipotalamusa na razdrazhenie pul'py zuba i Abeta-volokon sedalishchnogo nerva u koshki.

Responses of single units from lateral and medial areas of the posterior, tuberal and anterior hypothalamus to electrical stimulation of dental pulp and sciatic nerve A beta afferents were recorded in anesthetized curarized cats. 80.7%, 81.5% and 71.4% of units, respectively, responded to stimulation in posterior tuberal and anterior hypothalamus. The shortest latency of responses was recorded in the postero-lateral hypothalamus. Nociceptive responses in the lateral hypothalamus were of shorter latency than responses of medial hypothalamic units. Marked predominance of excitatory responses in the posterior hypothalamus and almost an equal proportion of excitatory and inhibitory responses in the tuberal and anterior hypothalamus were found. High degree of convergence (85.8%) of noxious and nonnoxious (sciatic nerve A beta afferents) impulses was revealed. Unidirectional, similar pattern of responses of convergent type neurons to stimulation of the tooth pulp and sciatic nerve A beta afferents indicate a nonspecific character of responses of the majority of polysensory neurons. 14.2% of hypothalamic units were monomodal, specific nociceptive neurons. Hypothalamic nociceptive units were characterized by a long recovery cycle (200-500 ms) and low reproducibility of responses to repetitive stimulation of the tooth pulp afferents (1.5-2/s). The neuronal organization of the nociceptive afferent system of the hypothalamus and the functional role of convergent and specific nociceptive neurons of the hypothalamus are discussed.

Effect of lesions of the anteroventral third ventricle (AV3V) on the development of hypertension in spontaneously hypertensive rats.

Lesions of the anteroventral third ventricle (AV3V), an angiotensin and osmosensitive region of the anterior hypothalamus, prevent or abort hypertension in a number of rat models. To determine if AV3V lesions alter hypertension in spontaneously hypertensive rats (SHR), lesions and control sham lesions were made in young SHR at 28 days of age. AV3V lesions had no effect on the development of hypertension in SHR. However, lesioned rats demonstrated significantly reduced pressor responses to intracerebroventricular injections of angiotensin II (AII) and hypertonic NaCl, and drinking produced by centrally administered AII. The depressor effect of central AII receptor blockade was also significantly attenuated in lesioned SHR. These effects appeared to be of central origin since the lesion did not affect the pressor action of intravenous AII or norepinephrine (NE). It is concluded that unlike other models of experimental hypertension (steroid-salt, one-and two-kidney renal, neurogenic) the development of hypertension in SHR does not depend upon the integrity of the AV3V region.

Hypothalamic deafferentation in the rat appears to discriminate between the anterior lobe and intermediate lobe response to stress.

Anterolateral deafferentation of the mediobasal hypothalamus prevented the increase of the plasma corticosterone concentration induced by ether, histamine and electric footshock. Hypothalamus deafferentation also prevented the ether stress-induced increase of the plasma levels of ACTH and beta-endorphin immunoreactivity (ACTHi, beta-ENDi). Infusion of isoproterenol evoked an increase of the plasma levels of corticosterone, ACTHi, beta-ENDi and alpha-MSH immunoreactivity (alpha-MSHi) in sham-operated rats. In rats with a deafferented hypothalamus, the responses of plasma corticosterone and ACTHi to isoproterenol were blocked but the responses of plasma beta-ENDi and alpha-MSHi remained intact. We conclude that circulating beta-ENDi after exposure to ether is of anterior lobe origin while circulating beta-ENDi after infusion of isoproterenol is of intermediate lobe origin.

Systemic and regional hemodynamic changes associated with anterior hypothalamic lesions in conscious rats.

Systemic and regional hemodynamics were determined with the radioactive microsphere technique either in conscious "sham-lesioned" Wistar rats or after bilateral electrolytic lesions of the nuclei of the anterior hypothalamus. Both mean arterial pressure (111 +/- 4 vs 152 +/- 3 mm Hg) and heart rate (376 +/- 15 vs 504 +/- 12 beats/min) were significantly increased 2 hours after lesioning (p less than 0.001). Although cardiac output tended to increase, it did not attain statistical significance; therefore this form of neurogenic hypertension is characterized by increased total peripheral resistance. Regional hemodynamics were measured 2 hours after placement of the lesions: skeletal muscle flow increased, renal cutaneous and splanchnic flows decreased, and brain and myocardial flows were preserved. These hemodynamic alterations were associated with significant elevations in plasma norepinephrine and epinephrine levels, and behavioral changes characterized by hypermotility, aggressitivity, and irritability, which resembled those seen during fighting and exercise.

Systemic and regional haemodynamics in anterior hypothalamic hypertension in spontaneously hypertensive and Wistar-Kyoto rats.

1. Systemic and regional haemodynamics were determined in conscious Wistar-Kyoto and spontaneously hypertensive rats with the radioactive microsphere technique after sham lesion or bilateral electrolytic lesion of the nuclei of the anterior hypothalamus. 2. Anterior hypothalamic lesions produced an increase in blood pressure, heart rate and cardiac output. 3. In the rats with lesions there were changes in regional haemodynamics: heart and skeletal muscle flow increased; renal, skin ans splanchnic flow decreased. 4. The haemodynamic consequences of ablation of the anterior hypothalamus were similar in both normotensive Wistar-Kyoto and spontaneously hypertensive rats. The haemodynamic pattern resembles that seen during fighting and exercise.

Suppression of sexual receptivity in the female hamster: neuroanatomical projections from preoptic and anterior hypothalamic electrode sites.

Electrical stimulation (ES) through fine-wire electrodes chronically implanted in the preoptic area and anterior hypothalamus suppressed the lordosis response in freely moving hormone-primed female hamsters. ES at these sites never induced or facilitated lordosis. When behavioral testing was completed small lesions were made at the tips of the electrodes, and the Fink-Heimer method was used to trace degenerating axons away from the sites of ES. This was done in an effort to determine the neural pathways important for the modulation of this behavior. The hypothalamic distribution of the stria terminalis was also charted for the hamster and was found to be similar to that in the rat, including projections to both the shell and core of the ventromedial nucleus (VMN). No single pattern of degeneration was common to all females showing ES-produced lordosis suppression. These data demonstrate that stimulation of several different pathways can produce behavioral states that are incompatible with the lordosis response. We suggest that ES in the medial preoptic-medial anterior hypothalamic continuum suppresses sexual receptivity by influencing neurons in the VMN region, while ES through more laterally placed electrodes suppresses receptivity by producing an incompatible state of behavioral activation, without directly influencing VMN region neural activity.

Fever: pathogenesis, pathophysiology, and purpose.

Fever appears to have evolved in vertebrate hosts as an adaptive mechanism for controlling infection. This phenomenon is produced by certain exogenous (largely microbial) stimuli that activated bone-marrow-derived phagocytes to release a fever-inducing hormone (endogenous pyrogen). Endogenous pyrogen, in turn, circulates to the thermoregulatory center of the brain (preoptic area of the anterior hypothalamus) where it causes an elevation in the "set-point" for normal body temperature. Warm blooded animals produced fever by increasing heat production (through shivering) or reducing heat loss (by peripheral vasoconstriction), whereas cold blooded animals do so only by behavioral mechanisms (seeking a warmer environment). This paper discusses current concepts that involve the mechanism of endogenous pyrogen production, the role of central transmittors, and the probable function of fever in combating disease.

Antagonism by indomethacin of neurogenic hyperthermia produced by unilateral puncture of the anterior hypothalamic/preoptic region.

1. In unanaesthetized rats, restrained at an ambient temperature of 24 degrees C, the anterior hypothalamic/preoptic (AH/PO) region was lesioned unilaterally by acute mechanical puncture.2. In control (no pre-treatment) rats, unilateral AH/PO puncture produced a neurogenic hyperthermia which began immediately, reached its peak magnitude (mean peak magnitude = +2.3 degrees C) within 60-90 min and persisted usually for 8-16 hr. At defervescence, core temperature fell to a level near that of the pre-lesioning base line.3. The prostaglandin synthesis inhibitor, indomethacin, administered I.P. at doses of 5 and 15 mg/kg 1 hr before puncture of the AH/PO region, attenuated the lesion-induced hyperthermia in a dose dependent fashion. The higher dose reduced peak magnitude by 80% and the 6 hr Fever Index by 88%. The vehicle used to dissolve the indomethacin (60% DMSO/40% saline) did not significantly attenuate the hyperthermia.4. In rats that were hyperthermic after AH/PO damage, indomethacin (10-15 mg/kg I.P.) caused core temperature to fall promptly to near the prelesion base line. Reversal occurred whether the indomethacin was injected while core temperature was still rising or late in the plateau phase of the hyperthermia.5. It is suggested that the neurogenic hyperthermia elicited by unilateral lesioning of the AH/PO region was mediated by prostaglandins released from injured tissue and possibly from extravasated blood. Evidence is cited indicating that the most likely sites of action of the released prostaglandins are the surviving portion of the AH/PO region on the punctured side and the intact contralateral AH/PO region.

[Electrical activity of the hypothalamus during stress]. / Elektricheskaia aktivnost' gipotalamusa pri stresse.

Chronic experiments were undertaken on rabbits to ascertain the multiunit activity of the anterior (AHA), medial (MHA), and lateral (LHA) hypothalamic areas during the immobilization stress. The immobilization excited the adrenocortical activity and changed the multiunit activity. The stress resulted in a decrease in the firing rate in most pools in the AHA and LHA, and an increase in the MHA.

Immediate hypotensive after-effects of posterior hypothalamic lesions in awake rats with spontaneous, renal, or Doca hypertension.

If the posterior hypothalamus contributes to elevate blood pressure in hypertension by increasing sympathetic vasomotor activity, then lesions of the posterior hypothalamus should lower blood pressure more in hypertensive than in normotensive rats. To test this hypothesis without complications caused by anaesthesia, aortic pressures were recorded from indwelling catheters in awake rats before and after selective hypothalamic destruction. In normotensive rats rats, bilateral lesions of the medial areas of the posterior hypothalamus always lowered blood pressure while those in the anterior hypothalamus slightly increased it. Heart rate responses varied widely and did not seem to contribute to the blood pressure changes. Posterior hypothalamic lesions of approximately the same size had significantly greater hypotensive after-effects in renal and spontaneously hypentensive rats than in normotensive or Doca hypentensive ones. These results imply that sympathetic overactivity emanating from posterior hypothalamic centres contributes to the blood pressure elevation in spontaneous or chronic renal hypentension but not in Doca hypertension. However, because of inherent weaknesses in the 'lesion method' and the complexity of blood pressure regulation in awake animals, other explanations are possible.