Currently used criteria for neuropathological diagnosis of Alzheimer's disease (AD) allow only the distinction of fully developed AD or ill-defined cases with less severe pathologic alterations. There is a need for a staging procedure that is able to supplement the currently used criteria, to allow for sufficient differentiation between the initial and intermediate stages of the illness, and to provide a characterization of the degree of involvement in the brain tissue of “nondemented, age-related controls.” The destructive process underlying AD is characterized by a typical distribution pattern of brain changes that is specific with respect to area, lamina, and even cell type. The most conspicuous change is the progressive deposition of abnormal proteins, both between and within the nerve cells. Conventional staining methods to identify these deposits lack sensitivity and specificity. Silver methods (specifically the Gallyas silver-iodide technique for neurofibrillary changes and the Campbell-Switzer silver-pyridin technique for brain amyloid) are by far the best suited to diagnostic work. They are inexpensive, simple to use, and far more reliable. This article describes the patterns of staining typically found with each of these techniques in the brains of patients with progressively severe AD and describes how the specific changes observed can be used as a staging system for diagnostic purposes.

Background:Reports in the literature on the effects of behavioral problems in patients with dementia on the decision to institutionalize the patient have shown conflicting results. Few studies have taken into account the possibility that specific behavioral problems may have differential effects on the decision to institutionalize the patient. Moreover, it is probably not patient behavior itself that causes nursing home placement (NHP), but caregivers’ emotional reaction to it. The aim of the present study was to examine the impact of specific behavioral subsyndromes and caregivers’ emotional reaction on NHP.

Methods:A total of 119 patients with dementia and their informal caregivers were followed up for 2 years. Time to NHP was measured in months from the date of the baseline interview to the date of NHP. Behavioral disturbances in the patient and caregivers’ emotional reactions were measured with the Neuropsychiatric Inventory (NPI). Cox regression analyses were used to determine the probability that caregivers would institutionalize the patient when patient behavioral problems or caregiver distress were present at baseline.

ResultsForty-one percent of the patients were institutionalized during the 2-year follow-;up. Caregiver distress related to patient behavior was a significant predictor of NHP, while behavior in itself did not predict NHP. Contrary to our expectations, we did not find a differential impact of specific aspects of problem behavior. Children caregivers, especially daughters, were associated with shorter time to NHP compared to spouses.

Conclusions:Our findings indicate that the caregiver's emotional reaction to patient behavior is more important than problem behaviors per se in the decision to institutionalize patients. Interventions aimed at teaching caregivers strategies to better manage difficult patient behaviors may provide caregivers with the necessary resources to continue care at home. Future interventions need to account for the specific needs and problems of different caregiver groups.

Rates of suicide differ markedly as a function of age and gender. In a great majority of countries that report suicide statistics, rates are higher in the elderly than in younger age groups. Few data are available to determine whether this age-related pattern of rates is reflected in a differential prevalence of other factors known to be associated with increased suicide risk. Using the psychological autopsy method, researchers have established the distribution of psychiatric diagnoses in samples of adolescents, young adults, and elders who have committed suicide, and in victims across the life course in community-based populations. Review of those studies reveals that affective disorders, substance use disorders, and their comorbidity are common in completed suicides of all ages. Although methodologic issues and cohort and period effects limit the conclusions that can be drawn, comparison by age within and between studies further suggests that depressive illness is more common and substance abuse less prevalent in later-life victims. That the aging process itself (biological, psychological, and social) may account for the observed pattern has important implications for further research and the design of intervention strategies. There is a need for more coordinated and comprehensive study of psychopathological correlates of suicide across the life course in a broad range of cultures.

Background: Most people with dementia in Western societies will eventually be placed in a nursing home. This can be stressful to those with dementia and to their families. The adjustment to this new caring environment by both residents and their family caregivers and the factors that influence this are the focus of this review.

Methods: A literature search of Embase, Scopus, and Medline databases of articles published in English between 1990 and 2011 using specified search terms was performed to examine this transition. The 174 titles located were screened and reference lists hand searched resulting in the 49 relevant articles included in this review.

Results: This decision and the subsequent adjustment period is a difficult time for people with dementia and their family caregivers. Admission has been linked to increased behavioral symptoms and in particular depression and agitation, decreasing cognition, frailty, and falls in people with dementia. For caregivers, guilt, depression, feelings of failure, and continuing burden but also improvement in quality of life have been variously reported. Research to determine what influences the trajectory of these different outcomes and the prevalence of positive outcomes for people with dementia is lacking. Successful transitions may be assisted by ensuring that the person with dementia has input into decision making, orientation procedures for the person with dementia and family member prior to and on admission, a “buddy” system for new arrivals, and a person-centered approach.

Conclusions: Adjustment to admission to residential care can be difficult for people with dementia and their family caregivers. Longitudinal research examining factors influencing the adjustment can provide a basis for intervention trials to improve this transition.

Background: We evaluated the combined and differential effects of physical, social and productive activities on cognitive decline and whether they were modified by the presence of the APOE-ε4 allele.

Methods: In a prospective cohort study of 1635 community-dwelling Chinese older adults aged 55 or older participating in the ongoing Singapore Longitudinal Aging Study, physical, social and productive leisure activities were assessed at baseline, and cognitive decline (at least one point drop) in MMSE scores between baseline and follow-up after one year.

Results: Cognitive decline was observed in 30% of the respondents. Controlling for age, gender, education and other risk factors, odds ratios (ORs) were significantly reduced in those with medium (OR: 0.60, 95% CI: 0.45–0.79) and high activity levels (OR: 0.62, 95% CI: 0.46–0.84). A stronger association was shown for productive activity (OR = 0.36), than for physical (OR = 0.78) and social activities (OR = 0.85). These associations showed statistically significant interactions with APOE genotype, being more pronounced in those with the APOE-ε4 allele.

Conclusion: Increased leisure activity, especially productive activities more than physical or social activities, was associated with a lowered risk of cognitive decline. APOE-ε4 genotype individuals appeared to be more vulnerable to the effects of low and high levels of leisure activities.

To evaluate nonpharmacologic interventions, caregivers (65 women, 38 men) and their dementia-diagnosed spouses (patients) were randomized to one of four treatment programs (cognitive stimulation, dyadic counseling, dual supportive seminar, and early-stage day care) or to a wait-list control group. Assessments occurred initially and at postintervention (3 months). Patients were evaluated on memory, verbal fluency, and problem-solving ability, and caregivers were assessed on marital interaction, emotional status, and physical health, along with stress, coping, and social support. Caregivers also completed a program evaluation. Repeated measures procedures showed that patients in the cognitive stimulation group demonstrated more improvement over time in cognitive outcomes, and caregivers decreased in depressive symptoms. Early-stage day-care and dual supportive seminar group caregivers reported a decrease in hostility and a decrease in use of negative coping strategies, respectively. Although qualitatively derived benefits differed across groups, similarities in program content reduced the potential for quantitative differentiation among the groups.

Background and objectives: Cognitive screening is a “first step” in detecting dementia and other neuropsychiatric syndromes and hence represents an important public health and clinical initiative. A plethora of cognitive screening instruments has been advocated in recent years, but the extent to which these instruments are used or their effectiveness is not well known. An International Psychogeriatric Association (IPA) survey was designed to determine which cognitive screening instruments were used most frequently by clinicians with special expertise in the neuropsychiatric aspects of old age and also to determine the ones considered most useful by these specialists.

Method: Under the auspices of the IPA, the survey was mailed in the fall of 2004 to all IPA members as well as members of the American and Canadian Associations of Geriatric Psychiatry. The survey inquired about demographic information, the frequency of use of cognitive screening instruments, and the value attributed to the cognitive screening instruments. Participants also had an opportunity to provide written commentary.

Results: A total of 334 completed surveys were processed. The majority of respondents were geriatric psychiatrists (58%). Of the 20 different instruments that were listed on the survey, only six were selected as “routinely” or “often used” by the survey respondents. These instruments in declining order were: (1) the Folstein Mini-mental State Examination; (2) the Clock Drawing Test; (3) Delayed Word Recall; (4) the Verbal Fluency Test; (5) Similarities; and (6) the Trail Making Test. “Effectiveness” and “ease of administration” were the test characteristics most highly predictive of frequency of use. Open-ended comments highlighted patient factors that continue to provide challenges, including ethnicity/culture, language, education/literacy, and sensory impairment. Respondents concluded that “no single test is adequate.”

Conclusions: Psychogeriatricians worldwide routinely use a relatively small number of brief cognitive screening instruments. Further evaluation is necessary as the need increases for cognitive screening guidelines that inform public health initiatives related to dementia and neuropsychiatric syndromes.

Staging methodologies are an essential tool in the assessment of disease severity in progressive dementing illness. Several different instruments have been developed for this purpose. One of the most widely used methodologies is the Global Deterioration Scale/Functional Assessment Staging (GDS/FAST) system. This system has been studied extensively and proven to be reliable and valid for staging dementia in Alzheimer's disease (AD) in diverse settings. One of the major advantages of this system is that it spans, demarcates, and describes the entire course of normal aging and progressive AD until the final substages of the disease process. Other advantages include: (a) greatly enhanced ability to track the longitudinal course of AD, (b) improved clinicopathologic observations of AD interrelationships, and (c) enhanced diagnostic, differential diagnostic, and prognostic information. This article presents a brief overview of the GDS/FAST staging system.

In a prospective study of more than 200 cases of dementia and 119 controls, annual technetium-99m–hexamethyl-propylene amineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) and annual medial temporal lobe (MTL) oriented X-ray computed tomography (CT) have been used to evaluate the diagnostic potential of functional and structural neuroimaging in the differential diagnosis of dementia. Some subjects have had up to 7 annual evaluations. So far, of 151 who have died, 143 (95%) have come to necropsy. Histology is known for 118, of whom 80 had Alzheimer's disease (AD), 24 had other “non-AD” dementias, and 14 controls with no cognitive deficit in life also had no significant central nervous system pathology. To compare the findings in the dementias with the profile of structural and functional imaging in the cognitively normal elderly, scan data from 105 living, elderly controls without cognitive deficit have also been included in the analysis. All clinical diagnoses were according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) criteria, and all histopathological diagnoses according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. Early data from this cohort have suggested that the combination of both MTL atrophy seen on CT with parietotemporal hypoperfusion on SPECT may predict the pathology of AD. The diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of the NINCDSADRDA and DSM-III-R criteria could be assessed in this cohort against the gold standard of histopathology. The diagnostic potential of CT evidence of MTL atrophy alone, SPECT evidence of parietotemporal hypoperfusion alone, and the combination of both of these scan changes in the same individual could then be compared against the diagnostic accuracy of clinical operational criteria in the pathologically confirmed cases. Furthermore, all of these modalities could be compared with the diagnostic accuracy of apolipoprotein E4 (Apo E4) genotyping to predict AD in the histopathologically confirmed cohort. In this population, NINCDS “probable-AD” was 100% specific, 49% sensitive, and 66% accurate; “possible-AD” was only 61% specific, but 93% sensitive and 77% accurate; and the combination of both “probable-AD” and “possible-AD” was 61% specific, 96% sensitive, and 85% accurate. DSM-111-R criteria were 51% sensitive, 97% specific, and 66% accurate. In the same cases and including the 105 living, elderly controls, the diagnostic accuracy of the Oxford Project to Investigate Memory and Aging (OPTIMA) scanning criteria showed CT alone to be 85% sensitive, 78% specific, and 80% accurate; SPECT alone had 89% sensitivity, 80% specificity, and 83% accuracy; and the combination of the two was 80% sensitive, 93% specific, and 88% accurate. The Apo E4 genotype was 74% sensitive but yielded 40% false positives in the histologically confirmed series. The diagnostic accuracy afforded by this method of CT and SPECT used alone is better than that of any established clinical criteria and reveals that the combination of MTL atrophy and parietotemporal hypoperfusion is common in AD, much less common in other dementias, and rare in normal controls. In the NINCDS-ADRDA criteria “possible-AD” cases, the combination of CT and SPECT findings alone were better in all diagnostic indices than the presence of Apo E4 alone in predicting AD. The frequent occurrence of MTL atrophy in AD and also in other “non-AD” dementias later in the course of the disease suggests the concept of medial temporal lobe dementia. This could explain some of the overlap of clinical profiles in the dementias, particularly as the dementia progresses, making clinical differential diagnosis difficult. In this context, the use of SPECT can significantly enhance specificity.

We used data from a 4-year prospective study of 2,558 primary care patients age 65 and older in a large staff model health maintenance organization to examine the association of clinically significant depressive symptoms and eight other chronic medical conditions with quality adjusted life years (QALYs). We developed linear regression models to examine the association of clinically significant depressive symptoms as defined by a score of 16 or greater on the Center for Epidemiological Studies Depression Scale and eight common chronic medical disorders at baseline with QALYs over the 4-year study period. Estimates of QALYs were derived from Quality of Well-Being Scale scores at baseline, at 2-year follow-up, and at 4-year follow-up. Individuals with clinically significant depressive symptoms at baseline had significantly lower QALYs over the 4-year study period than nondepressed subjects, even after adjusting for differences in age, gender, and the eight other chronic medical conditions. In terms of the entire study population, only arthritis and heart disease were more strongly associated with QALYs than depression.

Synaptic pathology has attained increasing attention as being central in the pathogenesis of Alzheimer's disease (AD). To address the question whether synaptic pathology in AD involves the whole synapse, or is limited to specific components thereof, we studied three different synaptic vesicle proteins (rab3a, synaptotagmin, synaptophysin) and also the presynaptic membrane protein GAP-43 and the postsynaptic protein neurogranin. The material included post-mortem brain tissue (frontal cortex, hippocampus, and cerebellum) from 8 patients with early-onset AD (EAD), 11 patients with late-onset AD (LAD), 6 patients with vascular dementia (VAD), and 9 control subjects. A reduction of all synaptic proteins was found in AD, more pronounced in EAD than in LAD, in both the frontal cortex (EAD 30% to 70% vs. LAD 82% to 88% of control value) and hippocampus (EAD 22% to 82% vs. LAD 76% to 89% of control value), whereas only minor changes were found in VAD. The finding that all synaptic proteins were reduced in AD suggests a degeneration and loss of whole synaptic elements that are more pronounced in EAD than in LAD.

The purpose of the study was to investigate the natural history of insomnia and its association with depression and mortality. In 1983, 1,870 randomly selected subjects aged 45–65 years answered a questionnaire on sleep and health. Of the 1,604 survivors in 1995, 1,244 (77.6%) answered a new questionnaire with almost identical questions. Mortality data were collected for the 266 subjects that had died during the follow-up period. Chronic insomnia was reported by 36.0% of women and 25.4% of men (χ2 = 9.7; p < .01). About 75% of subjects with insomnia at baseline continued to have insomnia at follow-up. Insomnia in women predicted subsequent depression (odds ratio [OR] = 4.1; 95% confidence interval [CI] 2.1–7.2) but was not related to mortality. In men, insomnia predicted mortality (OR = 1.7; 95% CI 1.2–2.3), but after adjustment for an array of possible risk factors, this association was no longer significant. Men with depression at baseline had an adjusted total death rate that was 1.9 times higher than in the nondepressed men (95% CI: 1.2–3.0).

The COVID-19 outbreak could be considered as an uncontrollable stressful life event. Lockdown measures have provoked a disruption of daily life with a great impact over older adults’ health and well-being. Nevertheless, eudaimonic well‐being plays a protective role in confronting adverse circumstances, such as the COVID-19 situation. This study aims to assess the association between age and psychological well-being (personal growth and purpose in life). Young–old (60–70 years) and old–old (71–80 years) community-dwelling Spaniards (N = 878) completed a survey and reported on their sociodemographic characteristics and their levels of health, COVID-19 stress-related, appraisal, and personal resources. Old–old did not evidence poorer psychological well-being than young–old. Age has only a negative impact on personal growth. The results also suggest that the nature of the COVID-19 impact (except for the loss of a loved one) may not be as relevant for the older adults’ well-being as their appraisals and personal resources for managing COVID-related problems. In addition, these results suggest that some sociodemographic and health-related variables have an impact on older adults’ well-being. Thus, perceived-health, family functioning, resilience, gratitude, and acceptance had significant associations with both personal growth and purpose in life. Efforts to address older adults’ psychological well-being focusing on older adults’ personal resources should be considered.

Background: Patients with dementia often receive poor end-of-life care, with inadequate pain control and without access to the palliative care services that patients with cancer are offered. This has been identified as an area of need in recent U.K. Government reports and by the Alzheimer's Society (U.K.). Our objective was to perform a systematic review of the scientific literature regarding the efficacy of a palliative care model in patients with dementia.

Methods: A systematic review was carried out to identify controlled trials that investigated the efficacy of palliative care in patients with dementia. Data sources included were Medline, EMBASE, PsycINFO, CINAHL, British Nursing Index, AMED, Cochrane Database of Systematic Reviews, Web of Science, Cochrane Central Register of Controlled Trials, International Standard Randomised Controlled Trial register, the NHS Economic Evaluation Database and the System for Information on Grey Literature in Europe. Other data was sourced from hand searches of papers identified on electronic databases and review articles.

Results: The search identified 30 review articles, but only four papers were eligible for full appraisal and only two of these met the full criteria for inclusion. These papers gave equivocal evidence of the efficacy for a palliative model of care in dementia.

Conclusion: Despite the increased interest in palliative care for patients with dementia there is currently little evidence on which to base such an approach. This may in part be due to the ethical difficulties surrounding such research, prognostic uncertainty in clinicians and the lack of clear outcome measures for patients who are unable to express their needs or wishes. Further systematic research is urgently needed to educate an important and developing area of clinical practice.

Background: Disturbances in rest–activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to enable the circadian clock to entrain to the 24-hour day. The purpose of this randomized, placebo-controlled, clinical trial was to test the effectiveness of morning bright light therapy in reducing rest–activity (circadian) disruption in institutionalized patients with severe AD.

Method: Subjects (n=46, mean age 84 years) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke – the Alzheimer's Disease and Related Disorders Association) AD diagnostic criteria were recruited from two large, skilled nursing facilities in San Francisco, California. The experimental group received one hour (09:30–10:30) of bright light exposure (≥2500lux in gaze direction) Monday through Friday for 10weeks. The control group received usual indoor light (150–200lux). Nighttime sleep efficiency, sleep time, wake time and number of awakenings and daytime wake time were assessed using actigraphy. Circadian rhythm parameters were also determined from the actigraphic data using cosinor analysis and nonparametric techniques. Repeated measures analysis of variance (ANOVA) was used to test the primary study hypotheses.

Results and conclusion: Although significant improvements were found in subjects with aberrant timing of their rest–activity rhythm, morning bright light exposure did not induce an overall improvement in measures of sleep or the rest–activity in all treated as compared to control subjects. The results indicate that only subjects with the most impaired rest–activity rhythm respond significantly and positively to a brief (one hour) light intervention.

Agitated behaviors in the nursing home pose a major problem for caregivers. Our data showed that the three syndromes of agitation—aggressive behaviors, physically nonaggressive behaviors, and verbally agitated behaviors—are differentially related to medical and psychosocial variables. Physically nonaggressive behaviors may be adaptive for a resident who presents a deteriorated stage of dementia, since these behaviors offer stimulation and exercise. Verbally agitated behaviors may be a form of help-seeking behaviors for residents with physical disease and depressed affect. Aggressive behaviors are those least understood, although these behaviors correlate with advanced stages of dementia and with poor interpersonal relationships. These findings should be a basis for further studies, with the ultimate goal being improved care for agitated elderly persons.