Diagnostic criteria for dementia with lewy bodies reconsidered.

The validity of the consensus criteria for dementia with Lewy bodies (DLB) has been questioned. The authors, therefore, performed analyses of 242 published cases with clinicopathological correlation of DLB. The prevalence of specific consensus criteria in 69 patients reported on by the Newcastle and Nottingham groups in England (Group N) were compared with their prevalence in papers from all other investigators (Group O). Analysis of the entire sample (Groups N and O combined) revealed 64% with parkinsonism, 66% with co-occurring parkinsonism and dementia, 39% with visual hallucinations (VH), and 30% with cognitive fluctuations (CF). Group N had significantly more CF and co-occurring parkinsonism and dementia. Dopaminergic drugs were associated with the presence of VH. Although selection factors may have contributed to investigator differences, parkinsonism and co-occurrence with dementia appear to be the most consistent diagnostic criteria for DLB.

CSF beta-amyloid, cognition, and APOE genotype in Alzheimer's disease.

OBJECTIVES: We examined the relationship between CSF amyloid beta peptide (A beta) concentration and AD severity in 31 probable AD patients and explored whether APOE genotype modifies this relationship. BACKGROUND: A beta deposition in AD brains has been correlated with disease severity and with APOE-epsilon4 allele frequency. Few studies have examined the effects of APOE genotype on the relationship between CSF A beta and disease severity in an antemortem sample. METHODS: Patients carried the clinical diagnosis of probable AD and did not have serious medical illness, current or past diagnosis of mood disorder, schizophrenia or alcoholism, or current psychotic features. The Mini-Mental State Examination (MMSE) was administered to the patient within 3 months of CSF collection. CSF was analyzed for A beta1-40 and A beta1-42 by sandwich ELISAs, and APOE genotype was determined by PCR run from blood. Correlations were performed between MMSE score and A beta1-40 and A beta1-42 concentrations while controlling for potential confounding variables. RESULTS: CSF measures of A beta1-40 and A beta1-42 concentrations were correlated with each other (r = 0.56, df = 28, p < 0.01). CSF A beta1-40 and A beta1-42 concentrations were positively correlated with MMSE score. The negative association between CSF A beta measures and disease severity remained significant after controlling for age (A beta1-40 and MMSE score: r = 0.46, df = 28, p = 0.01; A beta1-42 and MMSE score: r = 0.35, df = 28, p = 0.05). Among the APOE-epsilon3/3 homozygotes there was a significant positive correlation only between A beta1-42 and MMSE score (A beta1-42, r = 0.94, p = 0.02; A beta1-40, r = 0.79, p = 0.11). CONCLUSIONS: We hypothesize that an increased deposition of A beta in plaques results in decreased CSF A beta concentration. The stronger relationship between MMSE score and CSF A beta, specifically in APOE-epsilon3/3 homozygotes, suggests that patients with APOE-epsilon3/3 genotype may have different pathogenic mechanisms than the other genotypes for A beta deposition or clearance.

Experimental approaches to cognitive disturbance in Alzheimer's disease.

This paper reviews available and potential treatments for the cognitive disturbances associated with Alzheimer's disease. The neurochemical, neuropathological, and molecular-biological abnormalities associated with this disorder, as well as possible sites for pharmacological intervention, are discussed. These sites include genetic alterations in apolipoprotein E, amyloid precursor protein, and presenilin. Additionally, modification of amyloid processing, tau processing, and calcium regulation may have a role in future treatment. Intriguing epidemiological findings involving antiinflammatories, antioxidants, and estrogen for the cognitive deficits associated with Alzheimer's disease suggest the need for clinical trials of these agents. The current status of cholinesterase inhibitors, muscarinic receptor agonists, nicotine, and adrenergic and glutaminergic approaches to treatment are described.

Midlife crisis: helping patients cope with stress, anxiety, and depression.

Midlife may be associated with changes and losses, including declining health status, retirement, caregiving for aging parents, and unexpected responsibility for adult children or grandchildren. Suicide rates increase with age. Depression and substance abuse are common but often under-recognized and undertreated. The primary care physician can promote healthy aging by appropriately diagnosing and treating midlife depression and substance abuse, making appropriate referrals for psychotherapy, and utilizing the support and educational resources of community and national organizations.

Salivary cortisol and daily events in nursing home residents.

The authors evaluated the feasibility of using salivary cortisol as a noninvasive measure of hypothalamic-pituitary-adrenal (HPA)-axis responses to stressful events of daily living in elderly nursing home residents. Ten medically stable male nursing home residents (age 81.7 +/- 12.42) gave salivary samples before and after an assisted bath, and at corresponding times on the subsequent (control) day. Regression models, with measures of salivary cortisol on the bath and control days for two timepoints before the bath and four timepoints after the bath as the dependent variables, yielded significant effects of time, bath status, and day. Salivary cortisol testing is noninvasive and easy to collect from long-term care patients, including those with moderate degrees of dementia. It may be of use as a tool for studying the stressors associated with care, the determinants of HPA responses, and the consequences of hypercortisolemia in these vulnerable patients.

A risk-benefit assessment of tacrine in the treatment of Alzheimer's disease.

Tacrine, the first drug specifically approved for Alzheimer's disease, produces symptomatic improvement. The theoretical rationale behind treating Alzheimer's disease with tacrine is based on central cholinergic depletion. Tacrine is centrally acting, uncompetitive reversible inhibitor of acetylcholinesterase and butyrylcholinesterase. Multiple clinical trials support the effectiveness of tacrine in Alzheimer's disease. High dosages of tacrine are required for efficacy, with the potential for hepatic and mild gastrointestinal adverse effects. However, the benefits of tacrine currently outweigh its risks, and a trial of the drug should be offered to patients. As clinical experience with tacrine increases, the long term risk-benefit equation may be refined.

Helping foster children to mourn past relationships.

In spite of the increasing number of foster children who have had pathological relationships with their biological parents, there are relatively few reports of intensive therapy with these children. This paper focuses on the psychoanalytic psychotherapy of two young foster children whose treatment began shortly after placement. The paper describes the children's developmental problems, their conflicts and defenses, and the therapeutic process utilized to enable them to resume progressive development. The children were helped to mourn their past objects and to form more appropriate attachments to their foster parents.