Blaine S. Greenwald

Neuroanatomic Localization of Magnetic Resonance Imaging Signal Hyperintensities in Geriatric Depression

BACKGROUND AND PURPOSE Increased frequency and severity of signal hyperintensities have been regularly reported in elderly depressed patients compared with normal subjects, however, greater neuroanatomic localization of lesions has been limited. METHODS T2-weighted MRI scans in elderly depressed patients (n = 35) and normal comparison subjects (n = 31) were assessed for signal hyperintensities in lateralized discrete brain regions. RESULTS Logistic regression revealed that left frontal deep white matter (P<.005) and left putaminal (P<.04) hyperintensities significantly predicted depressive group assignment. CONCLUSIONS Findings suggest that greater neuroanatomic localization of hyperintensities than heretofore appreciated may relate to late-life depression.

Hippocampal/amygdala volumes in geriatric depression

BACKGROUND The hippocampus, amygdala and related functional circuits have been implicated in the regulation of emotional expression and memory processes, which are affected in major depression. Several recent investigations have reported abnormalities in these structures in adult and elderly depressives. METHODS Elderly DSM-III-R unipolar depressives (N = 40) and normal controls (N = 46) participated in a magnetic resonance imaging study (1.0T). Brain images were obtained in the coronal plane. Using established anatomical guidelines for structure delineation, volumetric measurements of left and right hippocampus and anterior hippocampus/amygdala complex were completed under blinded conditions using a semi-automated computer mensuration system, with patients and controls in random order. RESULTS Medial temporal volumes did not significantly distinguish either elderly depressed and age-similar normal control subjects, or late onset and early onset depressed patients (ANCOVA). Major overlap of measured volumes existed between patient and control groups. In depressives, hippocampal volumes significantly correlated with age, and cognitive and depression ratings, but not with number of prior depressive episodes or age-at-onset of first depression. CONCLUSIONS Hippocampal volumes do not discriminate a typical clinical population of elderly depressed patients from age-similar normal control subjects. If hippocampal dysfunction contributes to a diagnosis of syndromal depression in the elderly, such dysfunction does not appear to be regularly reflected in structural abnormalities captured by volumetric measurement as conducted. On the other hand, relationships between hippocampal volumes and clinical phenomena in depressives, but not controls, suggest potentially meaningful interactions between hippocampal structure and the expression of major depression in the elderly.

Qualitative magnetic resonance imaging findings in geriatric depression. Possible link between later-onset depression and Alzheimer's disease?

BACKGROUND Several clinical and neuroimaging investigations support the notion that underlying brain changes may relate to depression in older patients, especially those with a later-age initial episode. However uncertainty still exists about diagnostic and pathogenic significance of structural brain abnormalities in aged depressives, in part because many studies lack all-elderly and age-similar normal comparison populations. METHODS Brain morphology of elderly depressives (N = 30) and normal controls (N = 36) was compared by assessing magnetic resonance imaging (MRI) brain scans with qualitative criteria-based scales. Ratings included lateral and third ventricle enlargement, and cortical, medial temporal, and caudate atrophy. RESULTS Significant differences between depressed and control groups were not demonstrated. Later-onset depressives had significantly more left medial temporal and left caudate atrophy than early-onset counterparts of similar age. Medial temporal atrophy significantly correlated with cognitive impairment and was not related to physical illness. Depressives with medial temporal atrophy (N = 7) were older and had later age at onset of depression than those without such changes. Cerebrovascular disease risk factors did not predict MRI abnormalities. CONCLUSIONS Results indicate non-specificity and lack of homogeneity of qualitatively measured structural brain changes in geriatric depression, but suggest that pathology of specific, lateralized brain regions may be implicated in some later-onset patients. The relationship between medial temporal atrophy and late-onset depression raises the possibility that such patients may suffer from as-yet undeclared Alzheimers disease. Lack of association between cerebrovascular disease risk factors and brain changes suggests other pathophysiological contributions.

Clinical studies of the cholinergic deficit in Alzheimer's disease. I. Neurochemical and neuroendocrine studies.

Autopsy studies indicating that cholinergic neurons are selectively lost in patients with Alzheimers disease (AD) and senile dementia of the Alzheimer type (SDAT) suggest that peripheral markers for central cholinergic activity would be useful in diagnosis. The present studies found that cerebrospinal fluid (CSF) concentrations of acetylcholine (ACh) correlated with the degree of cognitive impairment (r = .70) in a sample of carefully diagnosed patients with AD/SDAT, but metabolites of other neurotransmitters were not related to cognitive state; this suggests that CSF ACh may be a valid measure of cholinergic degeneration. cortisol and growth hormone were measured in plasma samples drawn from patients and controls every 30 minutes from 2100 to 1100 hours the next day. Mean plasma cortisol concentrations were higher in patients with AD/SDAT than in controls and correlated inversely with CSF methoxy‐hydroxyphenylglycol (MHPG) (r = .61) and positively with degree of cognitive impairment (r = +.53); as anticholinergic drugs suppress cortisol this finding indicates that cortisol dysregulation may be a marker for abnormalities in other neurotransmitter systems, particularly the noradrenergic system. Growth hormone secretion was not different in patients and controls but was positively correlated with CSF MHPG (r = + .63).

A Controlled Study of MRI Signal Hyperintensities in Older Depressed Patients with and without Hypertension

To compare the frequency/severity of signal hyperintensities—likely markers of cerebrovascular disease—in the subcortical gray and deep white matter on magnetic resonance imaging (MRI) scans of brains of hypertensive and normotensive older depressed and nondepressed comparison subjects.

Relationships Between Behavioral Syndromes and Cognitive Domains in Alzheimer Disease: The Impact of Mood and Psychosis

OBJECTIVES Behavioral disturbances occur in nearly all Alzheimer disease (AD) patients together with an array of cognitive impairments. Prior investigations have failed to demonstrate specific associations between them, suggesting an independent, rather than shared, pathophysiology. The objective of this study was to reexamine this issue using an extensive cognitive battery together with a sensitive neurobehavioral and functional rating scale to correlate behavioral syndromes and cognitive domains across the spectrum of impairment in dementia. DESIGN Cross-sectional study of comprehensive cognitive and behavioral ratings in subjects with AD and mild cognitive impairment. SETTING Memory disorders research center. PARTICIPANTS Fifty subjects with AD and 26 subjects with mild cognitive impairment; and their caregivers. MEASUREMENTS Cognitive rating scales administered included the Mini-Mental State Examination; the Modified Mini-Mental State Examination; the Boston Naming Test; the Benton Visual Retention Test; the Consortium to Establish a Registry for Alzheimers Disease Neuropsychology Assessment; the Controlled Oral Word Test; the Wechsler Memory Scale logical memory I and logical memory II task; the Wechsler Memory Scale-Revised digit span; the Wechsler Adult Intelligence Scale-Revised digit symbol task; and the Clock Drawing Task together with the Clinical Dementia Rating Scale and the Neuropsychiatric Inventory. RESULTS Stepwise regression of cognitive domains with symptom domains revealed significant associations of mood with impaired executive function/speed of processing (Δr = 0.22); impaired working memory (Δr = 0.05); impaired visual memory (Δr = 0.07); and worsened Clinical Dementia Rating Scale (Δr = 0.08). Psychosis was significantly associated with impaired working memory (Δr = 0.13). CONCLUSIONS Mood symptoms appear to impact diverse cognitive realms and to compromise functional performance. Among neuropsychological indices, the unique relationship between working memory and psychosis suggests a possible common underlying neurobiology.

Hypochondriasis in the Elderly Depressed

The significance of hypochondriacal complaints in elderly depressives was explored. Sixty percent of patients had such symptoms on admission. Twelve percent were delusional. At discharge, hypochondriasis was present in 40% of the sample, with 0% delusional. Hypochondriasis was associated with anxiety (P < .05) and somatic concerns (P < .001), but not with complaints of depressed mood, suicidality, or short‐term outcome. In dependent physical illness ratings did not correlate with hypochondriasis, however nonpsychotropic medication use did (P < .01). Improvement in hypochondriacal complaints with treatment, yet persistence of less intense hypochondriacal concerns after remission suggests that these features may represent an admixture of state and trait phenomena in elderly depressives.

Clinical studies of the cholinergic deficit in Alzheimer's disease. II. Psychopharmacologic studies.

Two studies investigated the ability of physostigmine, given both intravenously and orally, to reduce symptoms of Alzheimers disease. Intravenous physostigmine significantly and reliably enhanced memory in 13 of 16 patients tested, but the dose producing the improvement varied among patients. Oral physostigmine decreased overall symptom severity in a reliable way in seven of 12 patients tested. The extent of improvement was correlated with the increase in mean cortisol secretion produced by physostigmine, suggesting that the drug improved behavior and cognition only to the extent that it had a specific central cholinomimetic effect. There was no significant association between response to physostigmine and results of a dexamethasone suppression test and physostigmine had no effect on growth hormone secretion.