For almost 90 years following the original description of Alois Alzheimer's patient and the identification of Alzheimer's disease (AD) (Alzheimer, 1907), physicians faced the bleak prospect of observing the inexorable and relentless decline in cognition, function, and behavior with little or no opportunity for therapeutic intervention. In the last 5 years clinicians have finally been provided with a class of medications, the cholinesterase (ChE) inhibitors, which have passed the test of efficacy and safety in the symptomatic management of AD and related dementias. With the arrival of donepezil, rivastigmine, and galantamine as the second generation of ChE inhibitors, a renewed and sustained interest in the diagnosis and care of AD patients might have been anticipated. However, there remains residual therapeutic nihilism and skepticism over the utility of these treatments in some quarters of the medical community and among some paying authorities. In moving forward and addressing these concerns, we must reflect carefully on the question, “What have we learned about the ChE inhibitors so far?”

Nutritional biochemistry is not a subject with which most psychiatrists, psychologists, and psychopharmacologists are familiar. A stream of recent epidemiological studies and clinical trials, however, indicates that understanding of nutritional biochemistry is soon going to be essential for anyone working with mentally ill patients. Those who are tempted to dismiss this statement as airy-fairy holistic nonsense will benefit from reading some recent issues of the American Journal of Psychiatry, British Journal of Psychiatry, Archives of General Psychiatry, Schizophrenia Research, Journal of Affective Disorders, and New England Journal of Medicine.

Pinner and Bouman's review article “To Tell or Not to Tell: On Disclosing the Diagnosis of Dementia” (pp. 127–137 in this issue) outlines the pros and cons of diagnosis disclosure to this diagnostic group. It is only over the past 10 years that the question of informing patients with dementia of their diagnosis has become topical, although the hard evidence for and against telling remains sparse, with much of the argument on either side being anecdotal. Paternalism is a common theme of surveys that examine the attitudes of spouse caregivers, relatives, and nonaffected older adults toward telling the diagnosis of dementia (Connell & Gallant, 1996; Erde et al., 1988; Holroyd et al., 1996; Maguire et al., 1996).

During the past 30 years, the growth of geriatric psychiatry services has been dramatic. Indeed, the majority of developed countries can boast of an impressive range of hospital-based, community-based, and long-term-care programs (Reifler & Cohen, 1998). For the most part, these services are traditional clinical services: The client (or caretaker) identifies a problem and the mental health professional offers comprehensive assessment and treatment.

A parted ev'n just between twelve and one, ev'n at the turning o' th' tide- for after I saw him fumble with the sheets, and play with flowers, and smile upon his finger ends, I knew there was but one way; for his nose was as sharp as a pen, and 'a babbled of green fields … A bade me lay more clothes on his feet. I put my hand onto the bed and felt them, and they were cold as any stone.

William Shakespeare, Henry V

Research suggests there has been a cultural change in the disclosure of diagnosis with most evidence held in cancer literature. This article reviews how disclosure of diagnosis relates to the field of dementia. Practitioners' attitudes and practice are being discussed, as are the attitudes and views of carers, peer groups, and patients. Practitioners show great variations in practice, with only around 50% of clinicians regularly telling patients with dementia their diagnosis. The majority of carers also appear to prefer the diagnosis to be withheld from the patient with dementia. However, most practitioners and carers would wish to know themselves if they had the illness. Although in contrast, studies on the views of elderly peer groups show that the vast majority wishes to be fully informed, views of patients with dementia regarding the area of disclosure are still lacking. Factors influencing the decision to disclose the diagnosis, including the degree of certainty of the diagnosis of dementia, the degree of insight of the patient, and the severity of the dementia, are investigated. The advantages and disadvantages of disclosure and the ethical issues are examined, as well as when or whether and how to disclose the diagnosis of dementia. Flexible guidelines regarding the process of disclosure are introduced.

Previous reports on the activities of essential endogenous antioxidants such as superoxide dismutase, catalase, and glutathione in dementia patients have not included a simultaneous quantitative assessment of dietary antioxidant intake. This is important because the reported differences in endogenous antioxidant levels among dementia patients may have reflected variations in the total antioxidants' intake. In this study we measured the levels of antioxidant vitamins A, C, and E in the diet of 81 dementia patients and controls at the same time as assessing blood levels of three endogenous antioxidants. Results showed a significant decrease in the intake of vitamins C (p < .001) and E (p < .01) in patients with severe Alzheimer's disease (AD) when compared to controls. Patients with mild/moderate AD differed from controls only in the intake of vitamin C (p < .01). The blood levels of catalase but not superoxide dismutase and glutathione were significantly decreased in the patients with severe AD when compared to controls (p < .01), patients with mild/moderate AD (p < .01), and patients with dementia with Lewy bodies (p < .05). The blood catalase levels of dementia patients, as a whole, were significantly and positively associated with the intake of vitamins A (p < .05), C (p < .01), and E (p < .05). The results indicated that dietary intake of vitamins A, C, and E may influence blood levels of catalase possibly through their antioxidant effects on free radicals. The data underscore the importance of concurrent quantitative assessment of nutritional intake when measuring endogenous antioxidant activities and support a role for antioxidant supplementation in the treatment of dementia disorders.

Alzheimer's disease (AD) is characterized by deterioration in the ability to perform activities of daily living (ADL) in addition to loss of cognitive function and behavioral changes. This decline in day-to-day functioning is increasingly recognized as a source of considerable social, health, and economic costs. Inability to perform ADL results in growing caregiver burden and may lead to the eventual need for alternative care or nursing home placement. The measurement of ADL, which enables monitoring of the effectiveness of therapeutic interventions, can be performed using a number of inventories including the Progressive Deterioration Scale (PDS), the Disability Assessment for Dementia (DAD), and the Alzheimer Disease Cooperative Study ADL (ADCS/ADL) assessment scale. Clinical studies using these and other scales have indicated that cholinesterase (ChE) inhibitors offer an effective approach to treating the functional decline of AD. Donepezil, rivastigmine, and galantamine have been shown in some studies to prevent or slow decline in ADL over treatment periods of one to two years. For instance, in a 24-week study in subjects with moderate to severe AD, donepezil-treated patients remained stable compared with the placebo-treated patients. Rivastigmine has shown improvement or stabilization of PDS scores in patients with mild to moderate disease following 26 weeks of treatment and slowed deterioration in patients with more severe disease. Evidence to date suggests that these agents may not be equally effective at slowing or stabilizing loss in ADL over time and that these differences may reflect differences in pharmacology. In addition to inhibition of acetylcholinesterase (AChE), these compounds have other putative differences in mechanisms of action. Galantamine allosterically modulates the nicotinic receptor and may prevent the loss of ADL. Rivastigmine robustly inhibits butyrylcholinesterase in addition to AChE and therefore acts as a dual ChE inhibitor. Comparative studies evaluating the differential effects of these ChE inhibitors on ADL are awaited.

Aims and Background: The International Psychogeriatric Association (IPA) aims to improve the mental health care of older people globally. With regard to depression, a number of key publications over the past decade have highlighted areas of progress and areas requiring further research. In order to help clarify what progress has been made, the author conducted a literature review of original research subsequent to three recent major reviews. Method: A literature search of four databases over the period 1998—October 2001. Publications with an abstract in English were studied to ascertain number of relevant publications; type of research methodology; topics; and where the research originated. Results: A total of 1,002 publications meeting predifined criteria were located. Fifty-nine percent were crossectional studies; less than 10% were randomized controlled studies. The most common themes were depression with comorbidity and etiology, accounting for almost half the papers, with stroke and Parkinson's disease the most frequently researched comorbid medical disorders, although interest in Alzheimer's disease, heart disease, hip fracture, and chronic lung disease appears to be increasing. There were comparatively few studies of psychological and psychosocial interventions. A quarter of the publications concerned major depressive disorder. There were striking variations in the origin of publications with two regions, North America and Northern Europe, accounting for two thirds of all publications but only 13.7% of the world's population aged 65 and over. Conclusions: Progress is being made but it might occur more rapidly and with greater scope with more international and cross-center collaboration.

Background: The purpose of this study was to examine if Type 2 diabetes mellitus is a risk factor for dementia in very old age, specifically for Alzheimer's disease (AD) and vascular dementia (VaD). Methods: We evaluated the risk of dementia in relation to Type 2 diabetes using a population-based sample of 702 individuals aged 80 years and older (mean age 83 years). A total of 187 persons received a dementia diagnosis. Thirty-one individuals had a diabetes diagnosis prior to onset of the dementia. Results: Cox proportional hazard analyses, adjusted for age, gender, education, smoking habits, and circulatory diseases, indicated an elevated risk to develop VaD (relative risk = 2.54, 95% confidence interval 1.35–4.78) in individuals with diabetes mellitus. No association was found between diabetes and AD. Conclusion: Type 2 diabetes is selectively related to the different subtypes of dementia. There is no increased risk of AD but more than a twofold risk of VaD in persons with diabetes.

Background: Studies on normal aging and cognitive functioning commonly describe early and more pronounced age-related changes in executive functions (EFs) compared to other cognitive abilities. Two of the three most common neurodegenerative disorders associated with aging (vascular dementia [VaD] and extrapyramidal [EP]-related dementia) show executive dysfunctions in their clinical presentation; and these cognitive deficits are not uncommon in the third one: Alzheimer's disease (AD). Methods: Nine EF tests (yielding 12 measures) were administered to 123 randomly selected community dwellers, aged 81 years and over, with the view to determine the effect of age on performance. Markers of AD, VaD, and EP-related dementia, as well as sociodemographic and psychological variables, were selected and their contribution to EF performance was investigated. Results: Multiple linear regression analyses revealed the greatest contribution to EF scores from the markers of AD and estimated IQ but not from the markers of VaD and EP-related dementia or from age. Conclusions: These findings suggest that chronological age acts as a proxy variable mediating the impact of other factors such as subclinical signs of neurodegenerative disorders and that it has little independent contribution to make. They also indicate the importance of cognitive abilities supported by posterior cortical circuits in EF problem resolution. This study demonstrates that cognitive decline is not an ineluctable process that is associated with “normal” aging but rather represents, in many cases, a byproduct of neurodegenerative disorders, albeit themselves highly age-related.

Objective: To describe the progression of patients with mild or moderate Alzheimer's disease (AD) to a severe stage using the Standardized Mini-Mental State Examination (SMMSE). Methods: A cohort of 206 patients was stratified according to their baseline SMMSE scores: mild (19–24) and moderate (10–18). Proportional hazards analyses were used to determine the hazard of switching into a severe stage, defined as SMMSE score < 10. Results: Among patients at the mild stage, 25% reached the severe stage within 2.6 years, and in the moderate group within 1.5 years. Patients with hallucinations at the mild stage experienced more rapid decline. The previous rate of decline was also found to be an important predictor. At the moderate stage, key predictors were lower SMMSE score and longer time since onset. Conclusions: Current SMMSE scores with other clinical details can be used to advise patients and caregivers about the expected progression of AD.

Background: Decline in physical functional ability is an intrinsic component of the dementia syndrome. Reductions in muscle mass and strength represent a major factor in the loss of functional ability. Although resistance exercise has been studied as a method for maintaining/recovering function in populations of frail older adults, people with dementia have been systematically excluded because of uncertainty about the reliability of outcome measurements. Objective: The purpose of this study was to determine the test-retest reliability of a battery of established performance-based measures of strength and function among subjects with dementia. Setting: A hospital-affiliated adult day-care facility. Subjects: Twelve of 28 older subjects with dementia of various etiologies were available for two assessments prior to implementation of a resistance-exercise intervention. Methods: Subjects underwent an assessment of lower extremity strength and physical function consisting of two recorded trials of bilateral isometric strength of the knee extensor, hip flexor, and dorsiflexor muscles, as well as hand grip strength; repeated chair stands, evaluation of usual- and maximal safe-gait speed over a 6-m course, and the Timed-Up-and-Go Test. The entire assessment was repeated approximately 1 week later. An average of the trials for each measurement was computed for each of the two assessment periods, and intraclass correlation coefficients (ICCs) for these paired measurements were estimated using STATA. Results: ICCs ranged from .56 for left iliopsoas to .77 for left dorsiflexors among the strength measures whereas measures of function ranged from .80 for number of steps in usual gait to .95 for time of fast gait. Conclusions: Performance-based measures of strength and function can be reliably assessed in older people with dementia, although measures of function appear to be more reliable than measures of strength.

Researchers have suggested that educational attainment and occupational status—indicators of cognitive and/or neurologic “reserve”—can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be “direct” (independent of occupational status), “indirect” (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subject included persons with “probable” or “possible” AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethinicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a “direct” effect of education on decline in MMSE, but no “indirect” effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus the protective effects of reserve may be established early in life, before people enter the workforce.

Behavioral and psychological symptoms of dementia (BPSD) are a common manifestation of Alzheimer's disease (AD) and other dementia syndromes. Patients experience prominent and multiple symptoms, which are both distressing and a source of considerable social, health, and economic cost. Development of symptoms is in part related to progressive neurodegeneration and cholinergic deficiency in brain regions important in the regulation of behavioral and emotional responses including the cortex, hippocampus, and limbic system. Cholinesterase (ChE) inhibitors offer a mechanism-based approach to therapy to enhance endogenous cholinergic neurotransmission. Studies using ChE inhibitors have demonstrated their clear potential to improve or stabilize existing BPSD. Differences have been noted between selective acetylcholinesterase (AChE) inhibitors (donepezil and galantamine) and dual ChE inhibitors (rivastigmine) in terms of treatment response. While donepezil has shown efficacy in moderate to severe noninstitutionalized AD patients, conflicting results have been obtained in mild to moderate patients and in nursing home patients. Galantamine has been shown to delay the onset of BPSD during a five-month study but has been otherwise poorly studied to-date. Both donepezil and galantamine have not as yet demonstrated efficacy in reducing psychotic symptoms or in reducing levels of concomitant psychotropic medication use. Studies with the dual ChE inhibitor rivastigmine in mild to moderately severe AD and in Lewy body dementia (LBD) have shown improvements in behavioral symptoms including psychosis. Improvements have been maintained over a period of up to two years. In addition, institutionalized patients with severe AD have shown symptomatic benefits with a reduction in the requirement for additional psychotropic drugs following treatment with rivastigmine. The psychotropic properties associated with rivastigmine may in part be mediated through effects on butyrylcholinesterase. Current treatment options are limited for patients with dementia syndromes other than AD. However, data concerning rivastigmine in patients with LBD and preliminary studies in Parkinson's disease dementia and vascular dementia suggest a role for ChE inhibitors across the spectrum of dementia syndromes. Finally, studies that incorporated a delayed start design demonstrate that ChE inhibitors may delay the progression of BPSD.

Objective: To assess the accuracy of clock drawing for detecting dementia in a multicultural, non-English-speaking-background population. Design: A prospective cohort study. Setting: A general geriatric medical outpatient clinic in southwest Sydney, Australia. Participants: Ninety-three consecutive new patients to the clinic who had a non-English-speaking-background country of birth (mean age 78.0 years). Measurements: The clock drawing test was conducted at the beginning of each clinic visit by a blinded investigator. Each patient was then assessed by a geriatrician who collected demographic data, administered the Modified Barthel Index, the Geriatric Depression Scale, and the Folstein Mini-Mental State Examination, and categorized each patient as normal or demented, according to DSM-IV criteria. Interpreters were used for participants who spoke a language other than English or who requested them. Each clock drawing was scored according to the 4-point CERAD scale and the previously published methods of Mendez, Shulman, Sunderland, Watson, and Wolf-Klein. Scoring was evaluated for reliability and predictive accuracy, using receiver operating characteristic (ROC) curve analysis. Logistic regression analysis was used to assess the potential interaction between level of education and each of the clock scoring methods. Results: Using ROC curve analysis, there was no significant difference between the clock scoring methods (area under the curve varied from 0.60 to 0.72). The most sensitive was the Mendez scoring method (98%), with a specificity of 16%. Specificity above 50% was found only for the Wolf-Klein method, with an intermediate sensitivity of 78%. Conclusions: There were no significant differences in the clock scoring methods used to detect dementia. Performance of the clock drawing test was modest at best with low levels of specificity across all methods. Scored according to these methods, clock drawing was not a useful predictor of dementia in our multicultural population.

Cognitive decline, commonly first recognized as memory impairment, is a typical feature of Alzheimer's disease (AD). Neuropathological changes in the cerebral cortex and limbic system lead to deficits in learning, memory, language, and visuospatial skills. The precise nature of cognitive dysfunction reflects the distribution of pathological changes in AD. These will vary along the disease severity continuum and may also depend on where the disease sits in the spectrum of dementia. For example, AD-related disorders such as Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) also show symptoms of cognitive decline and share several pathological features, including degeneration of cortical cholinergic and striatal dopaminergic neurons. In vascular dementia (VaD), there is often an unequal distribution of cognitive deficit, with severe impairment in some functions and relative sparing of others. Cholinesterase (ChE) inhibitors, which help restore acetylcholine levels in the brain, are licensed for the symptomatic treatment of AD and have shown additional benefit in related dementias. Physiological correlates of cholinergic function/dysfunction in the brain include regional cerebral blood flow, glucose metabolism, and cerebrospinal fluid levels of ChE enzymes. These variables represent valuable markers of the clinical efficacy of ChE inhibitors. However, direct assessment of cognitive improvement, stabilization or decline is usually considered the key efficacy parameter in clinical studies of ChE inhibitors in AD and related dementias. Large-scale, placebo-controlled clinical studies of ChE inhibitors have demonstrated efficacy in treating the cognitive impairments associated with AD. Randomized comparative studies of ChE inhibitors are now under way to directly compare symptomatic efficacy and effects on disease progression. Clinical trial data of the cognitive effects of ChE inhibitors in AD, LBD, PDD, and VaD are discussed in detail in this article. The benefits of long-term treatment on symptomatic improvement in cognition and further potential disease-modifying effects are highlighted.

Background and Objective: The pathophysiology and the neurobiology of the behavioral disturbances in Alzheimer's disease (AD) are far from understood. The aim of the study was to assess whether delusional AD patients have a specific pattern of regional brain atrophy. Methods: The setting of the study was the outpatients facility of a memory clinic. Subjects were 41 AD patients with mild dementia severity (Mini-Mental State Exam score of 22 ± 3, range 18 to 27). Delusions were assessed with the pertinent subscale of the UCLA Neuropsychiatric Inventory (NPI). Nondelusional (n = 22) AD and delusional (n = 19) AD were defined on the basis of absence (NPI delusions subscale = 0) or presence (NPI delusions subscale = 1 or higher) of delusions. Thirteen (68%) of the delusional patients had isolated theft delusions, and 6 (32%) had theft associated with another paranoid delusion (of jealousy or persecution). None of the patients had misidentifications or other delusions of nonparanoid content. Temporal lobe and frontal lobe atrophy were assessed with linear measures (radial width of the temporal horn, rWTH, and frontal index, FI) taken from computed tomographic films. Temporal and frontal asymmetries were computed as right/left ratio of the rWTH and FI. Results: AD patients without delusions had symmetrical enlargement of both temporal (8.1 ± 3.9 vs. 8.5 ± 4.5) and frontal horns (35.8 ± 4.8 vs. 35.9 ± 4.6). On the contrary, AD with delusions showed temporal horns larger to the right (9.1 ± 3.3 vs. 7.7 ± 3.1, p = .06) and the frontal horn to the left (35.7 ± 4.3 vs. 37.5 ± 4.2, p = .02). This different pattern was confirmed with a gender-adjusted repeated measures analysis of variance model (interaction term between asymmetry and group: F1,38 = 5.5, p = .03). Discussion: AD patients with delusions are characterized by a specific pattern of frontal and temporal asymmetry of brain atrophy, whereas nondelusional patients are symmetric. Because the asymmetry pattern of the delusional patients is similar to the physiological pattern of asymmetry of individuals without dementia, the data indicate that the absence of theft delusions in the mild stage of AD rather than their presence is associated with an abnormal asymmetry pattern.

Ninety-one mid- to late-stage dementia patients residing in nursing homes, along with their staff caregivers, participated in a study designed to assess whether training caregivers in sensitivity to nonverbal communication could enhance mood and reduce symptoms in patients and improve psychological well-being in caregivers. Patients and staff at three nursing homes comprised three groups that were randomly assigned to either a non-verbal sensitivity group, a behavioral placebo group that received instruction in the cognitive and behavioral aspects of dementia, and a wait-list control. Training consisted of 10 one-hour sessions taught by a clinical psychologist using prepared materials. Patient measures, which were taken at baseline and at 4 three-week intervals, included patient symptomatology (depression, agitation, behavioral symptoms), as reported by the staff caregivers, and positive and negative facial expressions of emotion elicited during a face-to-face interview and coded by trained research staff. Results indicated that positive affect increased sharply during the first 6 weeks after intervention in the nonverbal group, with the placebo and wait-list controls showing no change. There was also a decline in negative affect across time for all groups. Effects with respect to patient symptomatology did not reach significance. Caregivers in both training groups showed a decline in symptomatology, whereas the wait-list control group did not.

Background: The study was conducted to examine the relationships between functional decline, health risk factors, lifestyle practices, and demographic variables in two culturally diverse, community-based samples of White and Japanese American older adults. Design: The study was an analysis of data from two ongoing studies of aging and dementia in King County, Washington. Functional status at baseline was evaluated, and factors associated with functional decline over a 4-year follow-up period were identified. The sample included 1,083 Japanese American and 1,011 White cognitively intact, community-dwelling adults aged 65 and older, who had no functional limitations at baseline and participated in at least one follow-up examination. Results: In 4 years of follow-up, 70% of the subjects reported no increase in functional limitation, and fewer than 5% of subjects declined in five or more activities. Risk factors associated with functional decline included increased age, female gender, medical comorbidity (particularly cerebrovascular disease, arthritis, and hypertension), elevated body mass index, poorer self-perceived health, and smoking. Depression and diabetes were also significant for persons with the greatest functional decline over the 4-year follow-up. Japanese speakers were significantly less likely to decline over the follow-up period than White or English-speaking Japanese American subjects. However, Japanese speakers were more likely to discontinue participation during the follow-up period, and may also have been more likely to underreport symptoms of functional decline. Conclusions: The present study provides further support that healthy lifestyle practices and prevention of chronic disease are important for maintaining functional independence in older adults. Japanese-speaking subjects were less likely to decline over time, although this could be due in part to differential dropout and reporting bias. These findings have important implications for the design and interpretation of longitudinal studies of older adults. Researchers interested in the effects of ethnicity on health and aging should be cognizant of differences in recruitment and enrollment strategies among studies, and the ways in which these affect study findings. This study also demonstrates the importance of devoting adequate resources to minimize dropouts, and of including measures of health and functioning that are culturally equivalent and less reliant on self-report data.