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L L Heston

Publications and source records attributed to L L Heston.

At least 37 records · Page 2Linked to original sources
PubMed1993

Early detection of Alzheimer's disease: a statistical approach using positron emission tomographic data.

Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD.

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PubMed1993

Use of twin cohorts for research in Alzheimer's disease.

The causes of Alzheimer's disease (AD) remain a mystery despite the recent identification of several putative environmental risk factors and the discovery of several linked genetic loci and point mutations associated with the disease. Particularly uncertain is the generalizability of the genetic findings to the common forms of disease encountered in clinical practice or population research. Twin studies of AD can illuminate causal mechanisms, both genetic and environmental. This consensus document explores the rationale for such twin studies, as well as a number of methodologic problems that render them difficult to implement or interpret. We review existing twin studies of AD and note several ambitious new studies. Finally, we delineate several practical strategies for the near future of twin research in AD.

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PubMed1992

Longitudinal study of psychotropic drug use by elderly nursing home residents.

In this longitudinal study of patterns of use of psychotropic drugs by a cohort of elderly nursing home residents (N = 5,752), drug use was examined upon admission, 3 months later, and at discharge/end of study. At each time point, 17% of the cohort used neuroleptics. Half of the subjects discontinued neuroleptics at each time point; however, a similar number were initiated on the drug. Benzodiazepines were used by 21%, 15%, and 15% at each of the three time points, respectively. Twice as many people were taken off benzodiazepines as initiated on them following admission. The 5% rate of antidepressant use was constant across the three time periods, although only half of those who took antidepressants upon admission were also taking them upon discharge/end of study. The amount of change due to discontinuation of these drugs and adjustment in dosage levels challenges the stereotype of the "neglected psychotropic drug user" in nursing homes.

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PubMed1992

Inadequate treatment of depressed nursing home elderly.

OBJECTIVE: To determine the prevalence of antidepressant drug treatment among nursing home elderly with major depression. DESIGN: Survey early and late in nursing home stay. SETTING: Sixty Medicaid/Medicare-certified skilled nursing homes. PARTICIPANTS: Admission cohort of 5,752 residents age 65 or older in 1976 through 1983. MEASURES: Chart review by nurse-abstractors of physicians' diagnoses, drug used, and alertness rating. Diagnosis of depression equivalent to DSM-III-R major depression. RESULTS: Of 868 persons with a diagnosis of depression in the medical record, only 10% were treated with antidepressant drugs. More received neuroleptics and benzodiazepines than received antidepressants, but most (52%) received no psychoactive drug at all. A subset of 258 depressed persons had positive notations in their records supporting a mental status rating of "alert and oriented." Of that subset, only 15% received antidepressants. When followed from admission to discharge or end of study the prevalence rate of antidepressant drug treatment increased by 4%. CONCLUSIONS: In the late 1970's and early 1980's, even when the primary care physician made and recorded a diagnosis of depression, most such nursing home residents remained untreated, incorrectly treated, or inadequately treated.

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PubMed1991

Linkage of an Alzheimer disease susceptibility locus to markers on human chromosome 21.

We assessed linkage between Alzheimer disease (AD) and restriction fragment length polymorphisms (RFLPs) from human chromosome 21 in 8 families selected because of multiple occurrences of AD and large size. Sib-pair analysis demonstrated significant evidence for linkage between 2 markers (D21S1 and D21S11) and disease. Two markers, D21S13 and D21S52, did not yield evidence in favor of linkage to disease and a 5th, D21S16, was uninformative. The results confirm that a susceptibility locus for Alzheimer disease is located on chromosome 21. In contrast to other investigators who demonstrated linkage between AD and chromosome 21 loci, we found evidence in favor of linkage in both late- (greater than age 65) and early-onset families.

Alzheimer Disease↗
PubMed1991

Protocol for genetic testing in Huntington disease: three years of experience in Minnesota.

Molecular genetic testing for Huntington disease (HD) by linkage analysis of DNA markers close to the HD gene has been possible since the mid-1980s. Because of ethical and practical concerns about this kind of testing, most groups performing the test in the past have operated under lengthy research protocols designed to assess the psychological morbidity of the presymptomatic diagnosis of a fatal disease. Our approach to HD testing is service-oriented, and our testing process has been designed to be flexible, to meet the varying needs of our patients. Between 1988 and 1990, 87 inquiries about the test have been received; 22 inquiries had family structures which were unsuitable for linkage analysis. Eleven of the 37 individuals who entered the testing program have not completed it. Of 19 patients who have received DNA results, seven received an increased risk of carrying the HD gene, and ten, a decreased risk. For two additional individuals, nonpaternity resulted in a negligible risk for HD. Several of those consulted, or their spouses, have had continuing outpatient counseling since completing the test; none have required hospitalization. Our short-term results indicate that molecular genetic testing for HD can be performed safely in a clinical setting using our protocol. As molecular genetic testing for HD and other diseases moves out of research centers and into clinics, clinicians must devise practical strategies for providing the medical, genetic, and psychological services needed for the growing number of individuals who will seek such testing.

Genetic Linkage↗
PubMed1991

Heterogeneity in the inheritance of alcoholism. A study of male and female twins.

Genetic influence on risk for alcoholism was examined in a US treatment sample of 50 monozygotic (MZ) and 64 dizygotic (DZ) male and 31 MZ and 24 DZ female same-sex twin pairs. For the DSM-III composite diagnosis of Alcohol Abuse and/or Dependence, statistically significant MZ/DZ differences in concordance were found with male, but not female, twins. For specific diagnoses, MZ/DZ differences were found in male subjects for both Alcohol Abuse and Alcohol Dependence, while MZ/DZ differences in female subjects were found only for Alcohol Dependence. The male MZ/DZ concordance difference for composite diagnosis but not for Alcohol Dependence could be accounted for statistically by differences in age of onset between MZ and DZ probands. As with alcohol, differences in MZ/DZ concordance were found for DSM-III composite diagnoses of Other Substance Abuse and/or Dependence with male, but not female, twins. Using Epidemiological Catchment Area data to estimate the population base rates of both alcohol and other substance use disorders allowed for heritability analyses that showed genetic factors to have only a modest influence on overall risk in both sexes (heritability estimates of approximately 0.35 for male subjects and 0.24 for female subjects). However, evidence for heterogeneity in the pattern of inheritance was also found, suggesting forms of alcoholism that may be moderately to highly heritable.

Age Factors↗
PubMed1989

Family studies in Alzheimer's disease.

The risk for Alzheimer's disease (DAT) increases with increasing genetic relationship to an affected person. The empirical risk is highest for relatives of persons with relatively youthful onset. However, the incidence of cases with late onset may be underestimated because of a ceiling effect imposed by the human life span. Differences in age at onset between index cases (probands) and their affected relatives provide evidence that relative severity of illness is an important parameter of illness to note and analyze. These findings have important implications for genetic counseling. Other evidence from family studies provides leads to molecular genetics. Finally, studies of identical twins, though limited to a few pairs, strongly imply that, in principle, the development of Alzheimer's disease can be prevented.

Age Factors↗
PubMed1987

Pick's disease. Clinical genetics and natural history.

The relatives of 18 probands with neuropathologic evidence of Pick's disease were assessed with the main aim of estimating their risk for dementing illness. Fifteen secondary cases of dementia were discovered among relatives. The risks were significantly greater for probands' first-degree relatives than for second-degree relatives, which suggests an etiologic contribution from genes. Although numbers are small, the distribution of cases and their ages at onset are consistent in suggesting a sex effect, with male subjects more at risk than female subjects.

Adult↗
PubMed1986

Family studies of Alzheimer's dementia: results and prospects.

Studies of families located through a proband with dementia of the Alzheimer type have demonstrated transmission of the disorder within families, probably through shared genes. Increasing closeness of genetic relationship and increasing severity of illness are both associated with increasing risk to relatives. Families at high risk are especially valuable for studies of the biology of dementing illness including, in particular, their molecular genetics. Associations at several levels between Down's syndrome and Alzheimer's dementia provide important clues for molecular hypotheses.

Alzheimer Disease↗
PubMed1986

Fertility and parental age in Alzheimer disease.

The association of Alzheimer Disease (AD) with reduced fertility and increased parental age at time of birth were investigated in a sample of 126 individuals with AD. Relative to their normal siblings, maternal age at time of birth of the ADs was not significantly increased, nor were the AD individuals more likely to be later-borns in their sibships. The percentage of individuals bearing children was 75.7% for AD versus 70.8% for their normal siblings. For those ever bearing children, ADs produced slightly more children than their normal siblings (average of 3.92 versus 3.67). It was concluded that AD is not associated with either reduced fertility or increased parental age.

Adult↗
PubMed1986

Homosexuality in monozygotic twins reared apart.

We describe six pairs of monozygotic twins, in which at least one member of five pairs were homosexual, and one of the remaining pair was bisexual, from a series of 55 pairs, reared apart from infancy; all the female pairs were discordant for homosexual behaviour. This and other evidence suggest that female homosexuality may be an acquired trait. One male pair was concordant for homosexuality, while the other was not clearly concordant or discordant; this suggests that male homosexuality may be associated with a complex interaction, in which genes play some part.

Adult↗
PubMed1986

Seizures and myoclonus in patients with Alzheimer's disease.

We reviewed 81 patients with dementia and autopsy findings of Alzheimer's disease (AD) to identify patients with seizures or myoclonus after onset of dementia. Eight (10%) had seizures, and eight others (10%) had myoclonus. The incidence of seizures was 10 times more than expected in a reference population. Seizures occurred in any stage of AD, but myoclonus was often a late manifestation. Both seizures and myoclonus, individually or together, are manifestations of AD and may be seen at any time in the course of the illness.

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