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W M McDonald

Publications and source records attributed to W M McDonald.

At least 19 recordsLinked to original sources
PubMed1998

Magnetic resonance imaging correlates of depression in early- and late-onset Alzheimer's disease.

BACKGROUND: Depressive symptoms are frequent complications of Alzheimer's disease (AD). We hypothesized that AD patients with depression would be more likely than nondepressed AD patients to show deep white-matter, subcortical gray-matter, and periventricular hyperintensities on magnetic resonance imaging (MRI). METHODS: In a retrospective study of 31 AD patients, depression was characterized by clinical diagnosis (DSM-III-R major depression, depressive symptoms, or no depression), a clinician-rated depression scale, and informant ratings of premorbid (before memory disorder) as well as current depression using the NEO Personality Inventory (NEO-PI), and related to qualitative and quantitative ratings of MRI hyperintensities. RESULTS: In contrast to reports in nondemented elderly patients, there was no relationship between clinical diagnosis of major depressive episode and hyperintensities; however, clinician-rated depressive symptoms were higher in subjects with large anterior hyperintensities. In the early-onset AD group only, MRI abnormalities were related to greater premorbid depression, and less increase in depression after the onset of dementia, as rated by informants on the NEO-PI. CONCLUSIONS: Results highlight the need to consider early- and late-onset AD separately when assessing relationships between personality and MRI abnormalities, and to consider premorbid personality style when drawing conclusions about the etiology of depressive features seen in AD.

Age of Onset↗
PubMed1998

The use of rapid-rate transcranial magnetic stimulation (rTMS) in refractory depressed patients.

Rapid-rate transcranial magnetic stimulation (rTMS) allows for the noninvasive examination of the cerebral cortex. Recent studies have begun to investigate whether rTMS may be therapeutic for the treatment of depression. In the present study, the authors report on the safety and efficacy of rTMS in treating 50 patients with refractory depression. Overall, there were 21 responders (42%). Interestingly, 56% of the young patients responded, but only 23% of the elderly patients responded to rTMS. Overall, rTMS was well tolerated in all patients. Specifically, no patient developed a new onset of seizures during rTMS. The authors discuss the extant literature on rTMS for the treatment of depression along with future areas of research.

Aged↗
PubMed1996

Magnetic resonance imaging changes in putamen nuclei iron content and distribution in normal subjects.

To study patterns of iron deposition in the putamen in aging, we reviewed brain magnetic resonance imaging (MRI) scans of 56 normal subjects. We developed the Signal Hypointensity in the Putamen (SHIP) Scale, a semiquantitative measure, to evaluate putamen nuclei for extent of iron deposition relative to the globus pallidus. The SHIP score was highly reliable (kappa = 0.76) and significantly correlated with age (P < 0.0001). We found that age-related iron deposition in putamen nuclei follows a characteristic pattern along a posterolateral-to-anteromedial gradient. This gradient may be related to the microvasculature of the putamen. Other studies are needed to replicate our findings in patients with affective and other neuropsychiatric disorders and to clarify the pathophysiological mechanisms that govern these changes.

Adult↗
PubMed1996

Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study.

The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intractable Parkinson's disease (PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined "on/off" Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.

Adult↗
PubMed1996

The diagnosis and treatment of mania in the elderly.

Mania in late life is often complicated by comorbid medical conditions, medication intolerance, and inadequate medication response. Lithium remains the primary medication in the acute and prophylactic treatment of mania in the elderly. However, certain anticonvulsants (valproic acid and carbamazepine) have a number of advantages, including a more tolerable side effect profile and increased efficacy in subgroups of patients, such as patients with secondary mania due to neurological and other medical disorders. Future research is needed to focus on the double-blind trials of somatic treatments, including ECT, in the elderly.

Age of Onset↗
PubMed1995

Alzheimer's disease in the National Academy of Sciences-National Research Council Registry of Aging Twin Veterans. III. Detection of cases, longitudinal results, and observations on twin concordance.

OBJECTIVES: To detect cases of Alzheimer's disease (AD) in a large population of twins living throughout the United States and to examine concordance for AD in twins as a function of age and genotype for apolipoprotein E (APOE). SETTING: Nationwide survey. DESIGN: Multistage screening and field evaluation beginning with two telephone interviews and culminating with laboratory tests, longitudinal neuropsychological measures, physician examination, and diagnostic consensus among experts. PARTICIPANTS: Membership in 1990-1991 of intact pairs in the National Academy of Sciences--National Research Council Registry of veteran twins, then aged 62 to 73 years. MAIN OUTCOME MEASURES: Completeness of case detection was examined in collateral studies. Zygosity and APOE genotypes were determined by restriction mapping. Concordance was calculated by the proband method. RESULTS: Ninety subjects who screened positively for AD were studied in person, and 60 whose differential diagnoses included AD were followed up, as were their co-twins. Sensitivity of screening was estimated at greater than 99%, but 24% of subjects refused participation after initial screening. Seven of 38 diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually met criteria for probable or possible AD (prevalence estimate, 0.42%, 95% confidence interval, 0.29% to 0.56%), with good interrater reliability (intraclass r = .86). Excluding one discordant pair with unknown zygosity, concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4 genotype at APOE, but there were no affected co-twins of 15 probands with onset before age 70 years, no epsilon 4 allele, and no family history of AD. The mean (SD) period of discordance in the latter pairs was 11.3 (3.3) years. CONCLUSIONS: The multistage case-detection approach achieved reliable and valid diagnoses of AD with high apparent sensitivity but substantial attrition after initial screening. Genetic influences in AD at this age are limited, except among homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack the epsilon 4 allele are not rare, and their condition appears to have little genetic influence. They should be ideal for studies on environmental cause of AD.

Aged↗
PubMed1995

Arteriosclerotic depression.

Depression is a psychiatric syndrome seen in about 1-2% of elderly patients. When depression is seen for the first time late in life, genetic and psychosocial factors appear to be less important. Structural changes in the brain appear to be more important. In this paper the author presents the concept of arteriosclerotic depression and relates the occurrence of structural changes in the brain to atherosclerosis and the structural changes to the occurrence of depression. Evidence in support of this concept is presented.

Age of Onset↗
PubMed1994

Geniculocalcarine hyperintensities on brain magnetic resonance imaging associated with visual hallucinations in the elderly.

Magnetic resonance scans of five geriatric patients presenting with formed visual hallucinations in the absence of other psychopathology were compared with those of 12 healthy elderly subjects for the presence and extent of subcortical and periventricular signal hyperintensity. While the number of discrete brain lesions did not differ between groups, scans from the patient group contained a higher incidence (100% vs. 50%) and greater mean size (11.1 vs. 2.9 mm) of periventricular signal hyperintensity in the posterior region. Peripheral visual acuity was impaired in all of the patients, but cerebrovascular risk factors were not elevated in this group. The authors suggest that structural abnormalities in the area of the primary visual pathway may predispose some older individuals, particularly those with poor peripheral visual acuity, to develop the symptom of visual hallucination.

Aged↗
PubMed1994

Proton spectroscopy of human brain: effects of age and sex.

1. The present study was done to assess the brain metabolites measured by proton magnetic resonance spectroscopy (MRS) in normal individuals. 2. Proton spectroscopy STEAM voxel technique with chemical shift imaging was used to provide localized metabolic information from the brains of 34 normal volunteers (15 males) between the ages of 21 and 75 years. 3. Choline, Creatine and N-acetyl aspartate (NAA) was lower in white matter than gray matter. Choline/NAA and choline/creatine ratios were also lower in white matter. The choline, creatine and NAA were lower in older subjects in the voxel representing cortical and subcortical gray matter. There were no differences between males and females. 4. This preliminary study suggests that age matching is essential for comparative studies of disease states using proton MRS.

Adult↗
PubMed1994

Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study.

We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.

Age Factors↗
PubMed1993

Neuroanatomical substrates of depression in the elderly.

The etiology of depression in the elderly is poorly understood. In this study, magnetic resonance imaging was used to evaluate the role of subcortical structures in the pathophysiology of depression in the elderly. Elderly depressed patients were found to have smaller caudate nuclei, smaller putaminal complexes and in increased frequency of subcortical hyperintensities compared with normal, healthy controls. These findings were more pronounced in patients with late-onset depression. Based on these findings, the authors discuss the role of the basal ganglia in the pathophysiology of depression in the elderly.

Age Factors↗
PubMed1993

Hypercortisolemia and hippocampal changes in depression.

Hypercortisolemia is a frequently observed abnormality in patients with major depression. It has been hypothesized that the hippocampus, as a major feedback site for glucocorticoids, is involved in the pathophysiology of hypercortisolemia. Some have in fact posited that the hippocampus is marked by diminished size in depressed patients with hypercortisolemia. We tested this hypothesis by examining the relationship between hippocampal volume, assessed with magnetic resonance imaging, and hypercortisolemia using the dexamethasone suppression test (DST) in a group of 19 depressed patients. No differences in hippocampal volume were observed between patients and control subjects (n = 30). Within the patient group, DST suppressors did not differ from DST nonsuppressors in hippocampal volume. However, a relationship between hippocampal volume and 11 p.m. cortisol concentration was observed after covariance adjustment for age and sex. Furthermore, significant negative correlations were observed between hippocampal volume and both age of depressive onset and number of hospitalizations. The results of this study therefore provide limited support for the hypothesis regarding an essential role of the hippocampus in the neuroendocrine elevation of glucocorticoids in depression.

Adult↗
PubMed1993

Diminished subcortical nuclei volumes in Parkinson's disease by MR imaging.

Parkinson's disease (PD) is associated with changes in the substantia nigra, which communicates with subcortical nuclei. This study investigates subcortical nuclei volume in PD in vivo by magnetic resonance (MR) imaging. Caudate, putaminal, and thalamic nuclei were measured on axial MR images using a point counting method and systematic sampling. PD patients (n = 21) had significantly smaller subcortical nuclei than age- and sex-matched controls (p < 0.001) and depressed patients (p < 0.01). The decline in PD was not correlated with age, sex, or cortical volume. Depressed patients had significantly smaller caudate and putaminal nuclei than controls (p < 0.05 and 0.01, respectively) but thalamic nuclei were not significantly different. Caudate, putaminal, and thalamic nuclei volumes of controls were significantly negatively correlated with age (r = -0.58, p < 0.01; r = -0.77, p < 0.001; r = -0.57, p < 0.01, respectively). Depressed subjects demonstrated a negative trend. Volumetric measurements by MR imaging may be a useful in investigating the role of the basal ganglia in neurological disorders.

Caudate Nucleus↗
PubMed1992

Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.

A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3 +/- 17 years old) in comparison with 50 age- and gender-matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2 +/- 1.6 cm3) compared with controls (6.2 +/- 1.7 cm3). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression.

Age Factors↗