Intelligence and blood pressure in the aged.

Diastolic hypertension was related to significant intellectual loss over a 10-year period among individuals initially examined in their 60's. Such loss was not found in their age peers in association with normal or mild elevations of blood pressure. Of the subjects initially examined at 70 to 79 years of age, none with hypertension completed the follow-up program, and those with normal and mildly elevated blood pressure showed some intellectual decline over the decade. At the initial examination, hypertension was related to lower intelligence test scores only among those subjects who subsequently did not complete the follow-up program. The results suggest that hypertension is related to intellectual changes among the aged.

Improvement of learning in the aged by modification of autonomic nervous system activity.

Partial blockade of beta-adrenergic end-organ response to the autonomic nervous system was effected in a group of older men by administration of propranolol. The result was improved performance in a learning task. The data support the hypothesis that the learning decrement found among older men is not simply a manifestation of structural change in the central nervous system but is, at least in part, associated with the heightened arousal of the autonomic nervous system that accompanies the learning task.

Uncomplicated general anesthesia in the elderly results in cognitive decline: does cognitive decline predict morbidity and mortality?

Elderly surgical patients constitute a unique surgical group. They require special consideration in order to preempt the long term adverse effects of anesthesia. This paper examines the proposition that general anesthesia causes harm to elderly patients with its impact being felt long after the anesthetic agents are cleared from the body. One complication, Postoperative Cognitive Decline (POCD), is associated with the administration of anesthesia and deep sedation. Its' occurrence may herald an increase in morbidity and mortality. Based on both human and animal data, this paper outlines a unitary theoretical framework to explain these phenomena. If this hypothesis proves to be correct, anesthesiologist should consider regional rather than general anesthesia for equivalent surgical procedures to reduce POCD and consequently achieving superior patient outcome.

Micronutrients and HIV-1 disease progression.

OBJECTIVE: To determine whether nutritional status affects immunological markers of HIV-1 disease progression. DESIGN: A longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. METHODS: Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. RESULTS: Development of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P = 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by zidovudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P = 0.041) and the AIDS index (P = 0.005). CONCLUSIONS: These data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Cognition and immune function in HIV-1 infection.

OBJECTIVES: To determine (1) whether there were differences in cognition between HIV-1-seropositive and HIV-1-seronegative homosexual men and (2), if so, whether these differences could be explained by the degree of immunosuppression [i.e., CD4 cell count and immunoglobulin A (IgA) levels]. DESIGN: A cross-sectional design was used to compare 66 HIV-1-seropositives (Centers for Disease Control stages II and III, n = 56; stages IVA and IVC-2, n = 10) and 37 HIV-1-seronegatives. The HIV-1-seropositives were classified into three immune groups based on their CD4 cell count (x 10(6)/l) and serum IgA level (mg/dl): (1) moderate [(n = 35) CD4 greater than 400, IgA less than 300]; (2) mixed [(n = 22) either CD4 greater than 400 and IgA greater than 300 or CD4 less than 400 and IgA less than 300] and (3) poor [(n = 9) CD4 less than 400, IgA greater than 300]. HIV-1-seronegatives formed the 'good' immune group (CD4 greater than 400 and IgA less than 300). METHODS: The four groups were compared on tests of verbal and visual memory, information-processing speeds, visuospatial skills, language processes, attention, psychomotor reaction time, and mental status. Factors other than HIV-1 sero-status that can influence cognitive performance were tested as covariates. RESULTS: HIV-1-seropositives had slower information-processing speeds and decreased verbal and visual memory, compared with HIV-1-seronegatives. These differences in cognition were not due to differential immunosuppression or to clinical status among the HIV-1-seropositives. CONCLUSIONS: Cognitive alterations occur in HIV-1-infected individuals before AIDS and appear to be independent of clinical status and degree of immunosuppression as measured by CD4 cell count and IgA levels.

Specific nutrient abnormalities in asymptomatic HIV-1 infection.

OBJECTIVE: To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. DESIGN: A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. SETTING: The study was performed on an outpatient basis at the University of Miami School of Medicine. PARTICIPANTS: One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. MAIN OUTCOME MEASURES: Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. RESULTS: Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. CONCLUSION: Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.

The relationship of age, anxiety, and serum immunoglobulins with crystallized and fluid intelligence.

Serum immunoglobulin concentrations (IgG, IgA, and IgM), cognitive performance (crystallized and fluid intelligence), and self-reports of anxiety were evaluated in 24 men and women 60-75 years, and 50 men and women, 30-45 years. Trait anxiety was an important factor relating to performance differences between the young and old on crystallized and fluid subtests. IgM was inversely related to performance in the older age groups. Anxiety was not related to serum immunoglobulin levels.

Histocompatibility antigens (HLA) and patterns of cognitive loss in dementia of the Alzheimer type.

Recent data suggest that a proportion of patients with primary neuronal degeneration of the Alzheimer type have the HLA-B7 antigen. However, the possibility that other differences might exist between patients with and without the marker has not been examined. We tested a range of cognitive skills in Alzheimer patients with and without the HLA-B7 to examine whether those individuals with the HLA marker would exhibit a profile of cognitive loss different from those without it. Our results indicate that patients with HLA-B7 antigens had selective attentional scores that were significantly lower than Alzheimer patients without the antigen. Neither group was significantly different in either memory capacity or retrieval from short-term and long-term memory. The data support the hypothesis that there may be more than one disorder in what is now referred to as dementia of the Alzheimer type.

Immunoglobulins, cognitive status and duration of illness in alzheimer's disease.

Immunologic changes have been reported in the dementing illnesses of mid and late life. The results of two studies of drug-free males meeting research diagnostic criteria for primary neuronal degeneration of the Alzheimer's type suggest that serum IgG levels decrease with the progression of dementia. Serum IgG levels were inversely correlated with duration of illness and the levels of psychiatric symptomatology. Performance on the mini-mental status examination was positively associated with serum IgG concentrations.

Evaluation of the quality of psychiatric care for the aged.

Older persons represent a high proportion of those receiving care in institutions because of behavioral problems; relatively few aged people are treated in mental health center and other outpatient settings. The author believes that the availability and accessibility of community services should be among the most important variables used in assessing quality of care for the aged. He encourages the establishment of new norms for the quality of services needed to restore and maintain maximum physical, psychological, and social integrity.

A clinic for the impaired elderly and their families.

The need for improving psychiatric services to the elderly and for recognizing the importance of the family in caring for the impaired elderly led to the establishment of the Geriatric and Family Services, an outpatient clinic. This clinic provides psychiatric, medical, social, nursing, and architectural evaluations and recommendations for impaired older persons and also provides support and practical advice to the family. Most of the clinic's patients suffer from a dementing illness; of this group most have dementia of the Alzheimer's type. The authors studied the appointment-keeping behavior of the patients and also surveyed the patients' families as an indication of the clinic's success. Out of 50 patients the broken-appointment rate, as well as the drop-out rate, was 2%; 90% of the families who responded to the questionnaire indicated they would recommend the clinic's services to others.

Homicide-suicide in older persons.

OBJECTIVE: The objective of this study was to determine the annual incidence of homicide-suicide and to compare patterns and antecedents in old and young spousal/consortial cases. METHODS: Homicide-suicide cases were ascertained in four medical examiner districts covering seven entire Florida counties from 1988 to 1994. The districts were chosen to determine rates in two regions of Florida, comparable in size of the total population and proportion of older persons. Annual homicide-suicide incidence rates per 100,000 population and homicide-suicides as a percentage of total homicides and total suicides separately were calculated by age group and Florida region. Complete medical examiner files were obtained, and 160 variables were coded from medical examiner reports to compare features and clinical characteristics by age and region. RESULTS: Annual incidence rates ranged from 0.3 to 0.7 per 100,000 for persons under age 55 and from 0.4 to 0.9 per 100,000 for persons age 55 and older, with higher rates in the older group every year but two. Cases of spousal/consortial homicide-suicide were the most common in both age groups. The younger couples in both regions were comparable, except for racial composition, but the older couples differed. West central Florida couples were in their seventies, Caucasian, usually married, and both in poor health; and there were indications of depression or alcohol abuse in half the perpetrators. Two-thirds of the southeastern Florida couples were Hispanic; there was a mean age difference of 18 years between perpetrators and victims; and verbal discord, physical violence, and separation were prominent antecedents. CONCLUSIONS: The base rate for homicide-suicide in both age groups was higher than that reported in previous studies. Spousal/consortial homicide-suicides were the dominant form, and although psychopathology was strongly implicated, homicide-suicides are violent lethal acts resulting from additive or multiplicative effects of diathesis, including culture, and stressful experiences.

Concentrations of desipramine in elderly women.

Seven elderly depressed women were given desipramine, and plasma concentrations of the drug were measured from blood samples drawn after a single dose and during long-term use. The concentrations were no different from those found in younger patients. Aging does not seem to alter the plasma concentration of desipramine, and the authors conclude that the increased incidence and severity of the drug's side effects are probably not due to high drug concentrations.

Are there clinical differences between familial and nonfamilial Alzheimer's disease?

OBJECTIVE: The purpose of the study was to determine whether there are differences in clinical characteristics in two groups of patients with Alzheimer's disease, those reported to have a family history of dementia and those without a family history of dementia. METHOD: Using a data set from an Alzheimer's disease patient registry, funded as part of a National Institute on Aging cooperative agreement, the authors made comparisons of sociodemographic and clinical variables in a group of 462 patients with Alzheimer's disease, 172 reported to have at least one first-degree relative with dementia and 290 classified with no family history. RESULTS: Patients with a presumptive family history differed from those without a family history in two ways: the course of dementia was described as having a fast rather than a slow progression from onset of symptoms to diagnosis, and caregivers reported a higher prevalence of family history of psychiatric disorders. There were no significant differences in age at onset, duration, female gender, aphasia and apraxia, handedness, family history of Down's syndrome, or number of children, brothers, and sisters. CONCLUSIONS: The association of faster course and family history of psychiatric disorders in the patients with a family history of dementia is consistent with the hypothesis of heterogeneity, but the overall results could also be explained by a genetic-environmental model of Alzheimer's disease.

An empirical evaluation of the Global Deterioration Scale for staging Alzheimer's disease.

OBJECTIVE: Although the Global Deterioration Scale has been widely used since its publication in 1982, its stages are based on implicit assumptions about the linearity, temporality, and interdependence of cognitive, functional, and behavioral impairment in Alzheimer's disease. The authors evaluated the validity of these assumptions and tested the hypothesis that psychopathology and functional impairment would occur in earlier stages than the Global Deterioration Scale predicts. METHOD: The analyses were based on data on 324 patients with Alzheimer's disease who were selected from a registry of such patients. Data analyses included 1) descriptive statistics on the frequency of psychiatric symptoms and difficulties with activities of daily living and 2) logistic regression, with symptoms and functional impairment as independent variables, to test for significant changes in patients' status between stages of the Global Deterioration Scale. RESULTS: More than 50% of the patients at stage 2 displayed psychopathology, and 32% had two or more symptoms. The significant increase in psychiatric symptoms occurred between stages 3 and 4, not between stages 5 and 6 as predicted by the Global Deterioration Scale. Impairment in functional status was observed at all stages, and significant increases occurred between stages 3 and 4 as well as between stages 5 and 6. CONCLUSIONS: Psychiatric symptoms and functional impairment occur earlier than predicted by the Global Deterioration Scale, and the rate of change is also different from that specified in the scale. Separate scales to describe cognitive, clinical, and functional status may be the best way to describe the illness until better multidimensional instruments are developed.

Plasma cobalamin levels affect information processing speed in a longitudinal study of HIV-1 disease.

OBJECTIVE: To determine whether information processing speed is influenced by change in plasma cobalamin status in human immunodeficiency virus type 1 disease. DESIGN: A longitudinal study, using autoregression, to evaluate the relationship between plasma cobalamin status and change in information processing speed assessed by Posner Letter Matching, Sternberg Short-Term Memory Search, Figure Visual Scanning and Discrimination of Pictures, and continuous paired associates learning tasks. SETTING: University of Miami (Fla) School of Medicine from fall 1987 through summer 1991. PARTICIPANTS: Eighty-four human immunodeficiency virus type 1-infected homosexual men aged 20 to 55 years. None of the subjects displayed acquired immunodeficiency syndrome-defining symptoms at baseline; over the course of the study, 9.5% progressed to acquired immunodeficiency syndrome. MAIN OUTCOME MEASURES: Biochemical measurement of plasma cobalamin; performance on information processing speed tasks. RESULTS: Significant improvement in the Posner Letter Matching NI-PI (Name Identity minus Physical Identity) differential was associated with becoming cobalamin adequate or remaining adequate. Becoming cobalamin deficient, in contrast, was associated with a significant decline in the speed of accessing overlearned name codes. CONCLUSION: Normalization of plasma cobalamin inadequacy in human immunodeficiency virus type 1 disease may provide significant improvement in the speed of retrieving overlearned information from long-term memory.

Cognition in early human immunodeficiency virus infection.

Relatively little is known about cognitive changes in early human immunodeficiency virus (HIV) infection. This study examined cognitive functioning in 46 HIV-positive gay men relative to an age and education equivalent group of 13 HIV-negative gay men. The HIV-positive men were asymptomatic except for lymphadenopathy or T4 counts less than 700. The cognitive battery measured language, memory, visuospatial, information processing speeds, reasoning, attention, and psychomotor processes. The HIV-positive group was significantly slower in processing information and performed significantly less well than the HIV-negative group on certain verbal memory measures. Deviations of 1 as well as 2 SDs from the norm/control group mean on four or more tests were observed in 43% and 22% of the HIV-positive subjects, respectively, compared with 8% and none of the HIV-negative subjects, respectively. The results suggest that cognitive inefficiency occurs in a subsample of individuals during early HIV infection.

Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.

Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.

Norepinephrine response in early HIV infection.

Norepinephrine response to a cold pressor test was investigated in 95 homosexual men in a longitudinal study of human immunodeficiency virus (HIV) infection. The baseline data obtained from 76 HIV+ and 19 HIV- subjects are included in this report. After the insertion of a venicatheter and following a 30 min rest, subjects immersed one of their hands in ice water for 2 min, and serial blood samples were obtained for the determination of catecholamine levels. The results show that the norepinephrine response in HIV+ subjects compared to that of HIV- subjects was blunted. Examination of the responses using linear and quadratic orthogonal polynomials suggested that these differences between the two groups were primarily a function of their rate of increase in norepinephrine levels. It was observed also that in HIV+ subjects, norepinephrine level peaked earlier than that in HIV- subjects. The data suggest that autonomic dysfunction is present in the early stages of HIV infection.

Abnormal pituitary-adrenocortical response in early HIV-1 infection.

The corticotropin-adrenocortical response to cold pressor challenge was investigated in a study of human immunodeficiency virus (HIV) infection. Data obtained from 16 HIV-1-positive and 28 HIV-1-negative subjects are presented in this report. After the insertion of a venicatheter and following 30 min of rest, the subjects immersed one of their hands in an ice-water mixture for 2 min, and serial blood samples were obtained for the determination of ACTH and cortisol levels. The results show a significant blunting in the ACTH response and marginally lower levels of cortisol, over all time points, in HIV-1-positive subjects compared to that in HIV-1-negative subjects.