Additional psychiatric illness by Diagnostic Interview Schedule in male alcoholics

Seventy-four male veterans entering an alcohol abuse treatment program were screened for additional psychiatric diagnoses using the Diagnostic Interview Schedule (DIS). Fifty-four of these also completed a questionnaire on personal and family drinking history. Over half (54.1%) had another diagnosis. The most common syndromes other than substance abuse were antisocial personality disorder, phobic disorder, and depression. In each of these cases, the presence of the additional disorder accelerated the course of the alcohol problem significantly. The difference in course between syndromes was dwarfed by the time of presentation by the difference between "pure" alcoholism and alcoholism with another diagnosis. The primary versus secondary distinction appeared to account for only a part of this effect.     

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.     

Circadian locomotor activity rhythms in Alzheimer's disease

Circadian motor activity rhythms in 19 severely demented, institutionalized patients with Alzheimer's disease (AD) were evaluated with small, waist-worn electronic monitors which recorded 5-minute epochs for 48 to 72 hours. Controls were eight normal subjects of the same age (71 to 73 years) in a similar environment. As expected, computer-assisted analysis indicated more than twofold average increases in nocturnal activity and in the proportion of nocturnal to total daily activity in the AD patients. In patients (n = 8) with virtually constant pacing, daytime activity was markedly increased over that of normal controls; these "pacers" also had a significantly decreased amplitude of the circadian activity rhythm compared with controls. Moreover, AD patients showed a marked phase-delay, with individual afternoon maxima (acrophases) averaging 2.1 hours later than in controls (p less than 0.005). These findings quantitatively document clinical observations that AD patients, and especially a subgroup with pacing behavior, have markedly disturbed levels and modulation of daily locomotor activity. They accord with reports of altered circadian rhythms of endocrine and other physiologic parameters in such patients. Activity monitoring may represent a relatively simple, objective measure with which to characterize demented patients and to assess responses to treatment.     

Management of severe Alzheimer's disease and end-of-life issues

The quality of life of individuals with severe Alzheimer's disease requires attention to three main factors: (1) availability of meaningful activities, (2) optimal management of medical issues, and (3) appropriate treatment of psychiatric symptoms. Preservation of ambulation and comfort and avoidance of depression are significant interfaces between these three main factors. Formulation of an advance proxy plan is important for ensuring that the patient's previous wishes or best interests are considered when decisions about treatment strategies are made. Decisions regarding treatment strategies should take into consideration decreased effectiveness of several therapeutic approaches in this patient population. Hospice care is appropriate for the terminal stage of Alzheimer's disease, but palliative care also can be provided in other settings.     

Effect of decreased mobility on body composition in patients with Alzheimer's disease

Randomly selected 50 patients with the diagnosis of probable Alzheimer's disease, hospitalized for long-term care in a Special Care Dementia unit, were examined. None of the patients were clinically malnourished although several had low cholesterol levels. The mean lean body mass, measured by bioelectrical impedance plethysmography, was 62.5% of total body mass. The average calorie intake was 2125+398 Kcal/day, ranging from 1300 to 2900 Kcal/day, and the body weight of most subjects was stable, with the average gain of 1 lbs in the previous three months. Eighteen patients ambulated independently, 14 required assistance, and 18 were non-ambulatory. The lean body mass index was associated with the patient's age and mobility status. These results indicate that patients with advanced dementia and compromised mobility have decreased muscle mass that may result in weight loss even in the absence of malnutrition.     

Sundowning and circadian rhythms in Alzheimer's disease

OBJECTIVE: The goal of this study was to determine changes of circadian rhythms induced by Alzheimer's disease and to explore relationships among rhythm disturbances, sundowning, and sleep disturbances in patients with Alzheimer's disease. "Sundowning" is the occurrence or exacerbation of behavioral symptoms of Alzheimer's disease in the afternoon and evening. METHOD: Circadian rhythms of core body temperature and motor activity were measured in 25 patients with diagnoses of probable Alzheimer's disease and in nine healthy individuals. The subjects with Alzheimer's disease were divided according to the occurrence of sundowning as determined by staff reports. RESULTS: The subjects with Alzheimer's disease had less diurnal motor activity, a higher percentage of nocturnal activity, lower interdaily stability of motor activity, and a later activity acrophase (time of peak) than did the healthy individuals. They also had a higher mesor (fitted mean) temperature, higher amplitude of the fitted cosine temperature curve, and later temperature acrophase than did the healthy subjects. The severity of sundowning was associated with later acrophase of temperature, less correlation of circadian temperature rhythm with a 24-hour cycle, and lower amplitude of temperature curve. CONCLUSIONS: These data indicate that Alzheimer's disease causes disturbances of circadian rhythms and that sundowning is related to a phase delay of body temperature caused by Alzheimer's disease.     

Prenatal protein malnutrition in rats enhances serotonin release from hippocampus.

The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- to 240-d-old male rats. The malnourished rats (denoted 6,25 group) were males born to dams fed a 6% casein diet during pregnancy and fostered at birth to dams fed a control (25% casein) diet. They were compared with males born to dams fed 25% casein diet. Tissue concentrations of serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, L-tryptophan and catecholamines in the hippocampal formation in the 6,25 group were similar to those of well-fed controls (25,25 group). However, a twofold greater basal serotonin efflux from hippocampal slices of 6,25 rats compared with slices from 25,25 rats was observed during a 20-min incubation period. Hippocampal [3H]paroxetine binding indicated that there was no alteration of apparent maximal binding and affinity of the serotonin transporter in the 6,25 rats. In addition, there was no difference in serotonin receptor binding in hippocampal membranes from 6,25 and 25,25 rats. The results indicate that prenatal protein malnutrition causes selective changes in central serotonin metabolism.     

Severe impairment of circadian rhythm in Alzheimer’s disease

Circadian rhythmicity was repeatedly determined in a patient with Alzheimer??s disease by measuring his core temperature with a rectal thermistor and motor activity by an ambulatory activity monitor. The first recording, performed 9 years after he was diagnosed with Alzheimer??s disease, showed well organized 24 hr circadian rhythm of core body temperature. The second recording, made four months later, showed very poor fit of core body temperature to 24 hour rhythm, but excellent fit with 36 hour rhythm. The third recording, made two months later, showed again good fit of core body temperature with 24 hour cycle. The last recording, which was performed 5 months later, showed almost complete disappearance of circadian rhythm of body temperature. These changes probably reflect gradual lengthening of the circadian cycle that at one point became extremely lengthened before returning to the 24 hr cycle.