Choices abound while we await that pharmacogenetic fix that will save each one of us from all that is our individual and collective fate, contingent of course upon panopticon surveillance of our genetic susceptibilities and environmental triggers. The past decade has offered hope to those families facing the impenetrable shroud characterizing cognitive decline and dementia. Sufferers and their physicians have a growing compendium of pharmaceutical therapeutic interventions to attempt to stave off the usual, if not necessarily mindful, course of illness progression. In January 2001, the acetylcholinesterase inhibitors donepezil, rivastigmine, and galantamine were made available in the National Health Service in the United Kingdom, and some are on the formulary of five provinces in Canada. Those provincial pharmacare programs still refusing to provide these therapies free to the elderly cite lack of evidence of efficacy, following Cochrane guidelines based upon systematic review of the best evidence available using randomized controlled trials. Advocates for public funding of the pharmaceutical agents, on the other hand, cite a narratively rich, heart felt host of behavioral and affective symptoms stabilized or boosted by these drugs. And so, the two solitudes are drawn between science and humanity, between the cold guardians of the public purse and the caring humanitarians.

Objective: This article analyzes the natural history of wandering behavior throughout the course of dementia. Design: Prospective, 10-year, longitudinal study of wandering behavior in dementia, with autopsy follow-up. Setting: Participants with dementia, living at home with a carer. All lived in Oxfordshire, UK. Participants: Eighty-six people with dementia who were living at home with a carer and who were able to walk unaided at entry to study. Measures: At 4-monthly intervals, the carers were interviewed using the Present Behavioural Examination to assess wandering behavior were distinguished. Results: Changes in wandering behavior were not generally related to gender, age, or time since onset of dementia. Onset of different types of wandering behavior showed some relationship with cognitive state. Various forms of increased walking first appeared during moderate dementia, each type typically persisting for 1 to 2 years. Late dementia was characterized by decreased walking and immobility. Conclusions: Wandering behavior in dementia can cause great problems for carers. There are different causes for such changes, some of which are related to cognitive ability, for example increased confusion results in ineffectual “pottering” and getting lost. Increased walking at night corresponds with disruption of diurnal rhythm.

Objective: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. Methods: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAOSPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. Results: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterio frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%, only 2AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. Conclusion: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

Background: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. Method: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for ≥ 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p < .05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for ≥ 12% of variance in the item after controlling for age and gender. Results: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging,.81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). Conclusion: This scale can be used to measure therapeutic response in AD.

Background/literature review: The prevalence of agitated behaviors in different populations with dementia is between 24% and 98%. Although agitated behaviors are potentially disruptive, little research attention has been focused on the effects of these behaviors upon nursing staff. The objectives of this study of demented patients in long-term-care beds at an acute care community hospital were to determine the frequency and disruptiveness of agitated behaviors; to investigate the associations of patient characteristics and interventions with the level of agitation; and to explore the burden of these agitated behaviors on nursing staff. Method: The study sample comprised 56 demented patients in the long-term-care unit during the study period. Twenty-seven staff who cared for these patients during three shifts over a 2-week period were interviewed to rate the frequency and disruptiveness of agitated behaviors using the Cohen-Mansfield Agitation Inventory, and the burden of care using a modified version of the Zarit Burden Interview. Data on patient characteristics and interventions extracted from the hospital chart included scores on the Barthel Index and Mini-Mental State Examination, the use of psychotropic medication, and the use of physical restraints. Results: Ninety-five percent of the patients with dementia were reported to have at least one agitated behavior; 75% had at least one moderately disruptive behavior. A small group of six patients (11%) had 17 or more disruptive behaviors. The frequency of most behaviors did not vary significantly by shift. Length of stay on long-term care, Barthel Index score, and the use of psychotropic medications were significantly associated with the number of agitated behaviors. The number of behaviors, their mean frequency, and their mean disruptiveness were all significantly correlated with staff burden. Discussion: The prevalence of agitated behaviors in patients with dementia in long-term-care beds at an acute care hospital is similar to that reported in long-term-care facilities. These behaviors are associated with staff burden.

Patients with dementia with lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline.

Objective: To investigate the effects of light to moderate alcohol consumption on cognitive performance. Design and Setting: A cross-sectional analysis including older Japanese Americans in King County, WA, enrolled in the Kame Project, a population-based study of cognition, dementia, and aging. Participants: 1,836 cognitively intact participants aged 65 and older who participated in the baseline (1992-1994) examination. Measurement: Cognitive performance was measured using the Cognitive Abilities Screening Instrument, reaction time (simple and choice), and a measure of vocabulary (North American Adult Reading Test). Results: Multivariate analyses were used to examine the relationship between cognitive performance and alcohol consumption at baseline with men and women together and then separately controlling for age, education, smoking, history of stroke, angina, hypertension, diabetes, and coronary heart disease. Findings showed lower cognitive test scores were observed for men who were either abstainers or in the heavy drinking group. For women, a linear relationship between alcohol consumption and cognitive performance was seen on two of the four measures of cognitive functioning. No significant difference in the association of drinking and cognitive function was identified within the different Japanese American subgroups. Conclusion: Results suggest a possible positive relationship between light to moderate drinking and cognitive performance in an aging Japanese American population. Additional long-term prospective and cross-cultural studies are needed to determine the generalizability of these findings to other aging cohorts.

Rapid transcranial magnetic stimulation (rTMS) applied to the left dorsal lateral frontal cortex has been shown to produce antidepressant effects. Older depressed patients, however, in one study showed a lower response rate than younger patients. The current study examined treatment response in 20 depressed, treatment-refractory patients (mean age 60.7 ± 9.8 years) given five sessions of rTMS at 20 Hz for 2 seconds over 20 trains at 80% of motor threshold or identical placebo stimulation, after patients had been withdrawn from their antidepressants. There were no significant differences in Hamilton Depression Scale scores either before or after treatment at 7 days' follow-up. There were three responders to active treatment and three to sham treatment and responders had significantly greater frontal lobe volume than nonresponders (p=.03). These findings suggest that the stimulation parameters used in this study were probably insufficient to produce treatment response and that frontal atrophy may interfere with the effectiveness of rTMS.

Objective: To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD). Methods: This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures. Results: Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild. Conclusion: Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD.

This study examined the demographic, medical, and psychiatric correlates of hallucinations and paranoid delusions reported by proxy informants for 822 elders aged 70 or older. This sample comprised people who were deemed unable to complete a direct interview in a large nationwide study of aging. Marital status, trouble with vision, and cognitive impairment were associated with report of both paranoid delusions and hallucinations. Depressive symptoms and stroke were associated with hallucinations only. These results suggest that inadequate external stimulation in the elderly leads to psychotic experiences.