Gary L. Gottlieb

Aging, Brain Disease, and Reserve: Implications for Delirium

Cognitive and brain reserve are well studied in the context of age-associated cognitive impairment and dementia. However, there is a paucity of research that examines the role of cognitive or brain reserve in delirium. Indicators (or proxy measures) of cognitive or brain reserve (such as brain size, education, and activities) pose challenges in the context of the long prodromal phase of Alzheimer disease but are diminished in the context of delirium, which is of acute onset. This article provides a review of original articles on cognitive and brain reserve across many conditions affecting the central nervous system, with a focus on delirium. The authors review current definitions of reserve. The authors identify indicators for reserve used in earlier studies and discuss these indicators in the context of delirium. The authors highlight future research directions to move the field ahead. Reserve may be a potentially modifiable characteristic. Studying the role of reserve in delirium can advance prevention strategies for delirium and may advance knowledge of reserve and its role in aging and neuropsychiatric disease generally.

Quantitative anatomic measures and comorbid medical illness in late-life major depression

The authors examined the individual and relative roles of atrophy, comorbid medical illness, and cerebrovascular risk factors in the pathogenesis of late-life major depressive disorder (MDD). They used magnetic resonance imaging techniques to study 28 subjects with late-life MDD, 29 healthy control subjects, and 34 subjects with probable dementia of the Alzheimer type (DAT). Depressed subjects showed increases in cerebrospinal fluid volumes comparable to the DAT group but significantly different from control subjects. High-intensity signals, but not measures of atrophy correlated significantly with cerebrovascular risk factor scores. A logistic regression revealed that both brain atrophy and medical illness are associated with an increased risk of developing MDD. Data suggest that both atrophy and comorbid medical illness increase the likelihood of developing MDD in late life.

Autonomous neurobiological pathways to late-life major depressive disorder: clinical and pathophysiological implications.

The objective of our study was to elucidate distinct paths to depression in a model that incorporates age, measures of medical comorbidity, neuroanatomical compromise, and cognitive status in a sample of patients with late-life major depressive disorder (MDD) and nondepressed controls. Our study was cross-sectional in nature and utilized magnetic resonance imaging (MRI) estimates of brain and high-intensity lesion volumes together with clinical indices of cerebrovascular and nonvascular medical comorbidity. Neuroanatomic and clinical measures were incorporated into a structural covariance model in order to test pathways to MDD. Our data indicate that there are two paths to MDD; one path is represented by vascular and nonvascular medical comorbidity that contribute to high-intensity lesions that lead to depression. Smaller brain volumes represent a distinct path to the mood disorder. Age influences depression by increasing atrophy and overall medical comorbidity but has no direct impact on MDD. These findings demonstrate that there are distinct biological substrates to the neuroanatomical changes captured on MRI. These observations further suggest that neurobiological mechanisms acting in parallel may compromise brain structure/function, thereby predisposing individuals to clinical brain disorders such as depression.

Prospective versus retrospective methods of identifying patients with delirium.

To determine if DSM‐III criteria or clinical or discharge diagnoses, reviewed retrospectively, are as accurate an indicator of the presence of delirium as prospective evaluation by a psychiatrist.

Differential diagnosis of dementia, delirium and depression. Implications for drug therapy.

SummaryDementia, delirium and depression are the 3 most prevalent mental disorders in the elderly. While dementia and depression are prevalent in the community, hospitals and nursing homes, delirium is seen most often in acute care hospitals. Much of the management of these syndromes is undertaken by primary care physicians rather than psychiatrists. Therefore, it is imperative that generalist physicians be adept at recognising, evaluating and managing patients with these syndromes.Because no diagnostic tests are pathognomonic of these syndromes, the differential diagnosis hinges on a careful clinical evaluation. The first step is to recognise which of the syndromes is present. Dementia is defined by a chronic loss of intellectual or cognitive function of sufficient severity to interfere with social or occupational function. Delirium is an acute disturbance of consciousness marked by an attention deficit and a change in cognitive function. Depression is an affective disorder evidenced by a dysphoric mood, but the most pervasive symptom is a loss of ability to enjoy usual activities. It is important to recognise that these syndromes are not mutually exclusive, as dementia frequently coexists with delirium and depression. Furthermore, physical diagnoses, such as chronic obstructive lung disease, congestive heart failure, stroke and endocrine disorders, are frequently associated with depressive symptoms. Given this, a comprehensive evaluation is mandatory.Laboratory tests are necessary to exclude concurrent metabolic, endocrine and infectious disorders, and drug effects. Imaging studies should be obtained selectively in patients with signs and symptoms, such as focal neurological findings and gait disturbances, which are suggestive of structural lesions: stroke, subdural haematoma, normal pressure hydrocephalus and brain tumours. Appropriate management involving pharmacological and nonpharmacological measures will result in significant improvement in most patients with these syndromes. Potentially offending drugs should be discontinued. In delirious patients the underlying illness must be treated concomitantly with the use of psychotropics, if necessary.Although no current medications have been shown to have a significant effect on the functional status of patients with the 2 most common causes of dementia, Alzheimer’s disease and multi-infarct dementia, the management of concomitant illness in these patients may result in improved function for as long as a year. Tacrine, an anticholinesterase inhibitor, improves cognitive function slightly in selected patients with Alzheimer’s disease over short periods. Finally, the treatment of depression with medications or electroconvulsive therapy (ECT) results in significant reductions in mortality and morbidity.

Geriatric Mental Health Services Research: Strategic Plan for an Aging Population: Report of the Health Services Work Group of the American Association for Geriatric Psychiatry

In November 1999, a working group of the American Association for Geriatric Psychiatry (AAGP) convened to consider strategic recommendations for developing geriatric mental health services research as a scientific discipline. The resulting consensus statement summarizes the principles guiding mental health services research on late-life mental disorders, presents timely and topical priorities for investigation with the potential to benefit the lives of older adults and their families, and articulates a systematic program for expanding the supply of well-trained geriatric mental health services researchers. The agenda presented here is designed to address critical questions in provision of effective mental health care to an aging population and the health policies that govern its delivery.

Loss of Dopamine D2 Receptors in Alzheimer's Disease with Parkinsonism But Not Parkinson's or Alzheimer's Disease

A significant proportion of patients with Alzheimers disease (AD) exhibit extrapyramidal features that are referred to as parkinsonism (AD/Park) to distinguish the clinical and pathological features that differ from Parkinsons disease (PD). Previous results from this laboratory have shown that, although the presynaptic components of the dopamine (DA) system are markedly affected in AD/Park, the pathology is not similar to PD (Murray et al. 1995; Joyce et al. 1997). In the present study, we determined whether the parkinsonian symptoms in AD/Park might also reflect changes in numbers of postsynaptic DA receptors. We analyzed the binding of [125I]epidepride biding to DA D2/D3 receptors and [3H]SCH 23390 to D1 receptors by autoradiography in the striatum of six patients with PD, nine patients with AD, seven patients with AD/Park, and 14 neurologically intact control subjects. D2 receptors were reduced in the caudate and putamen of the AD/Park group (by 42 and 27% of controls, respectively) but not reduced in AD or PD. D1 receptors were elevated by 36% in the putamen of the PD group. Dopamine receptor changes are, therefore, not similar in PD, AD, and AD/Park. The elevation in D1 receptors in PD may contribute to the unwanted side effects of L-dopa treatment. The loss of D2 receptors in AD/Park, not observed in AD lacking overt parkinsonian symptomatology, may contribute to the presence of parkinsonian features and lack of responsiveness to L-dopa.

Sleep disorders and their management: Special considerations in the elderly

Complaints of insomnia and disordered sleep are pervasive among the elderly, and reduced total sleep time and changes in sleep architecture are considered to be normal in the aging process. Additionally, numerous medical and psychiatric disorders that are highly prevalent in the geriatric population are known to affect sleep adversely. Epidemiologic data indicate that at least 5 million older adults suffer severe disorders of sleep and that most people with severe insomnia receive no treatment for this troubling symptom. However, although the elderly comprise only about 12 percent of the American population, between 35 and 40 percent of all prescriptions for sedative hypnotics are written for people over the age of 60. Moreover, approximately 23 percent of Americans over age 85 reside in long-term care facilities, and institutionalization is an important risk factor for disordered sleep and for sedative hypnotic prescription. Consequently, the evaluation of any sedative hypnotic agent must include substantial assessment of efficacy, safety, and tolerance in geriatric patients.

Delirium in the medically ill elderly: operationalizing the DSM-III criteria.

This prospective study determined the incidence and prevalence of delirium in 235 consecutive subjects over age 70 admitted to a general medicine hospital service. The DSM-III criteria for delirium were operationalized. Using accepted screening procedures, patients were referred for evaluation by a psychiatrist who determined whether delirium was present by applying explicit operational definitions to each of the DSM-III criteria. Data on presence and severity of each of the DSM-III symptoms were recorded. Analysis of these data indicates that the DSM-III criteria describe a discrete, recognizable syndrome. However, some of the symptoms are more specific than others in identifying the syndrome in this population.

MRI High-Intensity Signals in Late-Life Depression and Alzheimer's Disease: A Comparison of Subjects Without Major Vascular Risk Factors

The authors examined periventricular white matter, deep white matter, and subcortical magnetic resonance imaging (MRI) high-intensity signals in subjects with late-life depression, probable Alzheimers disease (DAT), and healthy, age-matched controls. All subjects were healthy and free of major vascular risk factors, including hypertension. MRIs were performed using a 1.5-tesla GE Signa scanner. T2 and proton-density-weighted images were analyzed by a neuroradiologist blind to the clinical status of all subjects. There were no statistically significant differences on any of the MRI indices between the groups studied. These data demonstrate that late-life depression, like DAT, in the absence of major vascular risk factors, is not associated with a significant increase in MRI high-intensity signals when compared to healthy, control subjects.