New horizon in improving ageing with improvisational theatre.

Cognitive decline, mental health and mindset factors can all affect the autonomy and well-being of older adults. As the number of older adults across the globe increases, interventions to improve well-being are urgently needed. Improvisational theatre (improv) and improv-based interventions are well-suited to address this need. Studies have shown that participation in improv-based interventions has a positive impact on mental health indicators, including depressive symptoms, well-being and social connectedness, as well as cognitive skills such as attention and memory. In addition, improv-based interventions have been beneficial for people with dementia, improving positive affect, self-esteem and communication. In this article, we describe improvisational theatre, or improv, and the reasons it has emerged from a form of spontaneous theatre that involves playfulness and creativity to an important tool to effect behavioural change in individuals and groups. We then review the literature on the effects of improv in ageing populations, with a focus on social, emotional and cognitive functioning. Finally, we make recommendations on designing improv-based interventions so that future research, using rigorous quantitative methods, larger sample sizes and randomised controlled trials, can expand the use of improv in addressing important factors related to autonomy and well-being in older adults.

Perceived Stress, Blood Biomarkers, and Cognitive Functioning in Older Adults.

INTRODUCTION: There is a substantial gap in knowledge regarding how perceived stress may influence the relationship between serum-measured biomarkers for Alzheimer's disease and cognitive decline. METHODS: This study consists of 1,118 older adult participants from the Chicago Health and Aging Project (CHAP) (60% Black participants and 63% female participants). Linear mixed effects regression models were conducted to examine the role of perceived stress in the association between three blood biomarkers: total tau (t-tau), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) on global cognitive decline. Stratified analysis by stress level was also conducted to evaluate the associations between each blood biomarker and baseline cognitive function and decline. All models adjusted for age, race, sex, education, time, and their interactions with time. RESULTS: The interaction of stress, NfL concentration, and time was statistically significant on global cognition (ß = -0.064 (SE = 0.028), p-value = 0.023) and on episodic memory (ß = -0.097 (SE = 0.036), p-value = 0.007). CONCLUSIONS: Greater stress level worsens the association between high NfL concentration and cognitive decline. Stress management interventions may be helpful to reduce rate of cognitive decline in individuals with high concentrations of NfL.

Depressive Symptoms, Glial Fibrillary Acid Protein Concentrations, and Cognitive Decline in a Cohort Study.

BACKGROUND: Little is known about how depressive symptoms and glial fibrillary acid protein (GFAP) concentrations taken together may influence cognitive functioning. Understanding this relationship may inform strategies for screening and early intervention to decrease the rate of cognitive decline. METHODS: This study sample includes 1 169 participants from the Chicago Health and Aging Project (CHAP), consisting of 60% Black participants and 40% White participants, and 63% female participants and 37% male participants. CHAP is a population-based cohort study of older adults with a mean age of 77 years. Linear mixed-effects regression models tested the main effects of depressive symptoms and GFAP concentrations and their interactions on baseline cognitive function and cognitive decline over time. Models included adjustments for age, race, sex, education, chronic medical conditions, body mass index, smoking status, alcohol use, and their interactions with time. RESULTS: The interaction of depressive symptomology and GFAP (ß = -0.105 [standard error = 0.038], p = .006) on global cognitive function was statistically significant. Participants with depressive symptoms including and above the cutoff and high log of GFAP concentrations had more cognitive decline over time, followed by participants with depressive symptoms below the cutoff and high log of GFAP concentrations, depressive symptom scores including and above the cutoff and low log of GFAP concentrations, and depressive symptom scores below the cutoff and low log of GFAP concentrations. CONCLUSIONS: Depressive symptoms have an additive effect on the association between the log of GFAP and baseline global cognitive function.

Temporal Patterns of Change in Physical and Cognitive Performance.

BACKGROUND: This study examined the relation between declines in physical and cognitive performance in older people. METHODS: A population-based cohort of 7 483 adults (average age 72 years) were interviewed. Physical performance was assessed with 3 standardized tests and a combination of 4 cognitive tests was used to assess cognitive function. Rate of change in physical and cognitive performance was determined for each interval between interviews. In mixed effects linear regression models adjusted for age, sex, race, and study time, and change in each factor was used to predict change in the other factor. We examined time associations by using changes in the predictor measured at 1, 2, or 3 intervals before the outcome change. RESULTS: Decline in cognitive function was most strongly predicted by physical decline in the same 3-year interval. The decline in cognitive function was weaker in the 1-time interval after the decline in physical function and was not significant in later intervals. When a decline in cognitive function was used to predict a decline in physical function, the results were similar. The strongest association occurred in the same time interval so that declines in cognitive and physical performance tend to occur together. CONCLUSIONS: Decline in cognition and physical function seem to occur together in a short timeframe. It is important to investigate the reasons for these changes that are short-term to guide the development of interventions.

Association of Whole Grain Consumption and Cognitive Decline: An Investigation From a Community-Based Biracial Cohort of Older Adults.

BACKGROUND AND OBJECTIVES: To examine the association of whole grain consumption and longitudinal change in global cognition, perceptual speed, and episodic memory by different race/ethnicity. METHODS: We included 3,326 participants from the Chicago Health and Aging Project who responded to a Food Frequency Questionnaire (FFQ), with 2 or more cognitive assessments. Global cognition was assessed using a composite score of episodic memory, perceptual speed, and the Mini Mental State Examination (MMSE). Diet was assessed by a 144-item FFQ. Linear mixed-effects models were used to estimate the association of intakes of whole grains and cognitive decline. RESULTS: This study involved 3,326 participants (60.1% African American [AA], 63.7% female) with a mean age of 75 years at baseline and a mean follow-up of 6.1 years. Higher consumption of whole grains was associated with a slower rate of global cognitive decline. Among AA participants, those in the highest quintile of whole grain consumption had a slower rate of decline in global cognition (ß = 0.024, 95% CI [0.008-0.039], p = 0.004), perceptual speed (ß = 0.023, 95% CI [0.007-0.040], p = 0.005), and episodic memory (ß = 0.028, 95% CI [0.005-0.050], p = 0.01) compared with those on the lowest quintile. Regarding the amount consumed, in AA participants, those who consumed >3 servings/d vs those who consumed <1 serving/d had a slower rate of decline in global cognition (ß = 0.021, 95% CI [0.005-0.036], p = 0.0093). In White participants, with >3 servings/d, we found a suggestive association of whole grains with global cognitive decline when compared with those who consumed <1 serving/d (ß = 0.025, 95% CI [-0.003 to 0.053], p = 0.08). DISCUSSION: Among AA participants, individuals with higher consumption of whole grains and more frequent consumption of whole grain had slower decline in global cognition, perceptual speed, and episodic memory. We did not see a similar trend in White adults.

Neuroticism, physical activity, and cognitive functioning in a population-based cohort of older adults.

BACKGROUND: Little is known about how physical activity influences the relationship between neuroticism and cognitive function and cognitive decline. METHODS: Data from the Chicago Health and Aging Project (CHAP) was utilized to conduct this study. CHAP is a population-based cohort study of chronic conditions in older adults. Participants completed in-home interviews cycles of three years from 1993-2012. Mixed effects regression models were conducted to test the associations between physical activity, neuroticism, and the interaction between neuroticism and physical activity on outcomes: global cognitive function, global cognitive decline, episodic memory, decline in episodic memory, perceptual speed, and decline in perceptual speed. Stratified mixed effects regression models by physical activity level were conducted to test the associations between neuroticism and global cognitive function and global cognitive decline. RESULTS: A total of 7,685 participants were eligible for this study. Participants were 62% female and 64% African American. We found statistically significant associations for the interaction of high physical activity and neuroticism on baseline global cognitive function (ß = 0.017 (SE = 0.007), p = .010) and on the interaction of neuroticism and high physical activity on baseline episodic memory (ß = 0.020 (SE = .009), p = .021) and on decline in episodic memory over time (ß = -0.003 (SE = .001), p = .039). CONCLUSION: Higher physical activity lessened the association between higher neuroticism and poor cognitive outcomes.

Dietary Sugar Intake Associated with a Higher Risk of Dementia in Community-Dwelling Older Adults.

BACKGROUND: We have limited evidence for the relationship of high sugar intake with dementia risk. OBJECTIVE: To determine whether high sugar intake is associated with an increased risk of dementia in community-dwelling older adultsMethods:This study included 789 participants of the Rush Memory and Aging Project (community-based longitudinal cohort study of older adults free of known dementia at enrollment), with annual clinical assessments and complete nutrient data (obtained by validated food frequency questionnaire). Clinical diagnosis of dementia is based on the criteria of the joint working group of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We used Cox proportional hazard models. RESULTS: 118 participants developed dementia during 7.3±3.8 years of follow-up. Those in the highest quintile of total sugar intake were twice as likely to develop dementia than those in the lowest quintile (Q5 versus Q1:HR=2.10 (95% CI: 1.05, 4.19) when adjusted for age, sex, education, APOEɛ4 allele, calories from sources other than sugar, physical activity, and diet score. Higher percent calories from sugar were positively associated with dementia risk (ß=0.042, p = 0.0009). In exploratory analyses, the highest versus lowest quintile of fructose and sucrose in the diet had higher dementia risk by 2.8 (95% CI: 1.38, 5.67) and 1.93 (95% CI: 1.05, 3.54) times, respectively. CONCLUSIONS: A higher intake of total sugar or total calories from sugar is associated with increased dementia risk in older adults. Among simple sugars, fructose (e.g., sweetened beverages, snacks, packaged desserts) and sucrose (table sugar in juices, desserts, candies, and commercial cereals) are associated with higher dementia risk.

Cognitive Activity Is Associated with Cognitive Function over Time in a Diverse Group of Older Adults, Independent of Baseline Biomarkers.

BACKGROUND: More frequent engagement in cognitive activity is associated with better cognitive function in older adults, but the mechanism of action is not fully understood. Debate remains whether increased cognitive activity provides a meaningful benefit for cognitive health or if decreased cognitive activity represents a prodrome of cognitive impairment. Neurological biomarkers provide a novel way to examine this relationship in the context of cognitive aging. METHODS: We examined the association of self-reported cognitive activity, cognitive function, and concentrations of three biomarkers in community-dwelling participants of a longitudinal, population-based study. Cognitive activity was measured at baseline by asking participants to rate the frequency of 7 activities: (1) viewing television, (2) listening to the radio, (3) visiting a museum, (4) playing games, such as cards, checkers, crosswords, or other puzzles or games, (5) reading books, (6) reading magazines, and (7) reading newspapers. Cognitive function was measured with a battery of four tests (Mini-Mental State Examination, Digit Symbol Test, and the immediate and delayed recall of the East Boston Test) averaged into a composite score. At baseline, we evaluated the concentration of total tau (tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: The study sample comprised 1,168 older participants, primarily non-Hispanic Blacks (60%) and women (63%). At baseline, they were an average of 77 years old with 12.6 years of education. Mixed-effects models showed that cognitive activity was associated with better cognitive functioning at baseline and over time. These relationships remained after each biomarker was added to the model. Over an average of 6.4 years of follow-up, cognitive activity was associated with cognitive decline in the model with tau (estimate = 0.0123; p value = 0.03) and was mildly attenuated in the models with NfL (estimate = 0.0110; p value = 0.06) and GFAP (estimate = 0.0111; p value = 0.06). Biomarkers did not modify the association between cognitive activity and cognitive function over time. CONCLUSION: The benefits of cognitive activity on cognition appear to be independent of biomarkers: tau, NfL, and GFAP, measured at baseline. More frequent cognitive activity may benefit the cognitive health of older adults with a wide range of potential disease risk and presentations.

Race and Apolipoprotein E-e4 Allele Status Differences in the Association Between Loneliness and Cognitive Decline.

OBJECTIVE: This study aimed to examine race and apolipoprotein E-e4 allele (APOE-e4) status differences in the longitudinal associations between loneliness and cognitive decline. METHODS: The study sample is composed of participants ( N = 7696, 64% Black participants and 36% White participants) from the Chicago Health and Aging Project, a population-based cohort study. Mixed-effects regression models were conducted to examine the longitudinal associations between loneliness on global cognitive function and individual tests of cognitive function. Models were also stratified by race and APOE-e4. RESULTS: A greater percentage of Black participants (17%) reported loneliness at baseline visit compared with White participants (12%). Black and White participants who were lonely individuals had a similar rate of decline in global cognitive function at 0.075 (95% confidence interval [CI] = -0.082 to -0.068) standard deviation unit (SDU) per year for Black participants and at 0.075 (95% CI = -0.086 to -0.063) SDU per year for White participants. Lonely participants with APOE-e4 had a higher rate of global cognitive decline at -0.102 (95% CI = -0.115 to -0.088) SDU per year than for lonely participants without APOE-e4 at -0.052 (95% CI = -0.059 to -0.045) SDU per year. CONCLUSIONS: The burden of loneliness and its relation to cognitive decline is higher among participants with APOE-e4 compared with those without APOE-e4. Loneliness is associated with cognitive decline in both Black and White participants.

Healthy lifestyle and life expectancy with and without Alzheimer's dementia: population based cohort study.

OBJECTIVE: To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer's dementia. DESIGN: Prospective cohort study. SETTING: The Chicago Health and Aging Project, a population based cohort study in the United States. PARTICIPANTS: 2449 men and women aged 65 years and older. MAIN EXPOSURE: A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay-MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). MAIN OUTCOME: Life expectancy with and without Alzheimer's dementia in women and men. RESULTS: Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer's dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer's dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer's dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer's dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1). CONCLUSION: A healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer's dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.

Properties of the Cognitive Function Battery for the MIND Diet Intervention to Prevent Alzheimer's Disease.

OBJECTIVE: To evaluate the properties of the cognitive battery used in the MIND Diet Intervention to Prevent Alzheimer's Disease. The MIND Diet Intervention is a randomized control trial to determine the relative effectiveness of the MIND diet in slowing cognitive decline and reducing brain atrophy in older adults at risk for Alzheimer's dementia. METHODS: The MIND cognitive function battery was administered at baseline to 604 participants of an average age of 70 years, who agreed to participate in the diet intervention study, and was designed to measure change over time. The battery included 12 cognitive tests, measuring the 4 cognitive domains of executive function, perceptual speed, episodic memory, and semantic memory. We conducted a principal component analysis to examine the consistency between our theoretical domains and the statistical performance of participants in each domain. To further establish the validity of each domain, we regressed the domain scores against a late-life cognitive activity score, controlling for age, race, sex, and years of education. RESULTS: Four factors emerged in the principal component analyses that were similar to the theoretical domains. In regression equations, we found the expected associations with age, education, and late-life cognitive activity with each of the four cognitive domains. CONCLUSIONS: These results indicate that the MIND cognitive battery is a comprehensive and valid battery of four separate domains of cognitive function that can be used in diet intervention trials for older adults.

Genetic risk, adherence to a healthy lifestyle, and cognitive decline in African Americans and European Americans.

INTRODUCTION: We investigated the role of genetic risk and adherence to lifestyle factors on cognitive decline in African Americans and European Americans. METHODS: Using data from the Chicago Health and Aging Project (1993-2012; n = 3874), we defined the genetic risk based on presence of apolipoprotein E (APOE) ε4$\varepsilon 4$ allele and determined a healthy lifestyle using a scoring of five factors: non-smoking, exercising, being cognitively active, having a high-quality diet, and limiting alcohol use. We used linear mixed-effects models to estimate cognitive decline by genetic risk and lifestyle score. RESULTS: APOE  ε4$\varepsilon 4$ allele was associated with faster cognitive decline in both races. However, within APOE  ε4$\varepsilon 4$ carriers, adherence to a healthy lifestyle (eg., 4 to 5 healthy factors) was associated with a slower cognitive decline by 0.023 (95% confidence interval [CI] 0.004, 0.042) units/year in African Americans and 0.044 (95% CI 0.008, 0.080) units/year in European Americans. DISCUSSION: A healthy lifestyle was associated with a slower cognitive decline in African and European Americans.

Thera-prov: a pilot study of improv used to treat anxiety and depression.

Background: Improvisational theater exercises (improv) are used in various settings to improve mental health and medical outcomes. However, there is little documented evidence of the effectiveness of these interventions.Aims: We developed a short-term, group intervention that used improv exercises in a therapeutic manner to treat psychiatric patients.Methods: We evaluated the feasibility, acceptability and five clinical outcomes (depressive symptoms, anxious symptoms, self-esteem, perfectionism and satisfaction with social roles) of this intervention in an outpatient setting. Participants were 32 patients with symptoms of anxiety and depression and who had variable exposure to psychiatric treatment.Results: In paired samples t-tests, participants demonstrated reduced symptoms of anxiety (t(31) = 4.67, p < 0.001) and depression (t(31) = 3.78, p = 0.001), and improved self-esteem (t(31)= -3.31, p = 0.002) following the intervention. There was a trend towards reduction of perfectionism (t(31) = 1.77, p = 0.087), but no substantial change in rated satisfaction with social roles. Effect sizes were medium for reduction in symptoms of depression and anxiety.Conclusions: The results of this study indicate that a brief intervention based on improv exercises may provide a strong and efficient treatment for patients with anxiety and depression.

Association of cognitive activity and neurocognitive function in blacks and whites with HIV.

OBJECTIVE: Older persons with HIV are at risk for impaired cognition, yet there is limited information on modifiable factors associated with neurocognitive function in this group. DESIGN: This is a cross-sectional observational study of cognitive activities and neurocognitive function. METHODS: We examined the relation between frequency of cognitive activity and current neurocognitive performance in 176 older persons with HIV [70% African American, 76% men; mean age = 58.7 (SD = 5.5); mean education = 13.2 (SD = 2.8)]. RESULTS: In linear regression models adjusted for demographic variables, we found that higher frequency of cognitive activity was associated with better cognition in global cognition, semantic memory, and perceptual speed. Subsequent models that examined the role of race demonstrated that the association was significant only among Blacks for global cognition, episodic memory, working memory, and perceptual speed (interaction of cognitive activity by race: Estimate range = 0.38-0.55; all P < 0.05). CONCLUSION: Greater frequency of cognitive activity is associated with better neurocognitive function in older persons with HIV, particularly older Blacks. Longitudinal studies are needed to assess the relation of cognitive activity to change in neurocognitive function in older persons with HIV.

Loss of basic lexical knowledge in old age.

BACKGROUND: Basic lexical skills are hypothesised to be relatively preserved in mild dementia, but clinical studies have reported inconsistent results. METHODS: More than 400 older Catholic nuns, priests and brothers recruited from groups across the USA completed annual evaluations for up to 15 years, died and underwent brain autopsy. Each clinical evaluation included administration of a 20-item word reading test and a 15-item vocabulary test, which were combined to form a composite measure of word knowledge. In a uniform neuropathological examination, Alzheimer's disease pathology was quantified with a composite index of plaques and tangles, and the presence of gross and microscopic cerebral infarctions and Lewy bodies was recorded. RESULTS: The post-mortem level of Alzheimer's disease neuropathology was linearly related to rate of decline in word knowledge. Decline was nearly fourfold faster at a relatively high level of pathology (75th percentile) compared with a relatively low level (25th percentile). Neocortical (but not nigral or limbic) Lewy bodies and gross (but not microscopic) cerebral infarction were also associated with a more rapid decline in word knowledge. Effects for word reading and vocabulary were similar, except that gross cerebral infarction was associated with accelerated decline in vocabulary, but not in word reading. CONCLUSION: Common neuropathological changes associated with late-life dementia impair word knowledge in old age, calling into question the use of word knowledge tests to estimate premorbid cognitive ability.

Demographic adjustments for the Spanish version of the WAIS-III.

The Spanish version of the third edition of the Wechsler Adult Intelligence Scale (WAIS-III) by TEA Ediciones is an excellent addition to available instruments for Spanish speakers. The Spanish norms function similarly to US norms for individuals aged 16-35. The norms become increasingly different for individuals 35 and older, seemingly because of the lower levels of formal education of the older Spanish cohorts. Using data from a random half of the Spanish sample, the authors developed regression equations to adjust the scaled scores for individuals with a low level of education. The adjustment is made to the level that would have been expected if the individual had 12 years of education, the median level of education of the US norms. The article includes the methodology and values necessary to make the adjustments. The scaled scores were then adjusted for individuals on the second random half of the Spanish sample and compared to the United States norms. The results showed the adjustments succeed in bringing the Spanish norms closer to the US norms.

A battery of tests for assessing cognitive function in older Latino persons.

With the proportion of older Latinos in the United States rapidly growing, dementia is expected to be an increasing public health problem in this segment of the population. Yet relatively few cognitive test batteries have been developed for evaluating older Spanish-speaking persons. We selected a battery of cognitive tests used in cognitive aging studies of English speakers, adapted it for Spanish speakers, and administered it to 66 older Latinos (mean age=71.1, SD=8.1). The results of a factor analysis supported grouping the tests into the same 5 functional domains identified for English speakers. Composite measures of performance in each domain were positively related to education and, with some exceptions, inversely related to age. The results suggest that this battery may be useful in epidemiologic research on cognition in older Latinos.

The Spanish translation and adaptation of the Uniform Data Set of the National Institute on Aging Alzheimer's Disease Centers.

Researchers from Alzheimer's Disease Centers (ADCs) across the United States with expertise in the assessment of Spanish-speaking elderly collaborated to create the official Spanish version of measures in the Uniform Data Set of the National Institute on Aging Alzheimer's Disease Center Program. The present article describes this project, whose primary goal was to create Spanish instruments with cultural and linguistic equivalence to the English versions. The resulting Spanish versions make provisions for variations among Spanish-speaking groups in the United States of different nationalities, socio-cultural, linguistic, and educational backgrounds. A consensus-based translation and adaptation approach was used, and guiding principles and specific components of this process are summarized. The Spanish translation and adaptation of the Uniform Data Set measures became available online to ADCs in April 2007. Its creation is important, as the resulting effort provides standardized measures for the collection of cross-sectional and longitudinal data on a large cohort of Spanish-speaking elders across the country and facilitates collaborative research among ADCs.

Social engagement and cognitive function in old age.

We examined the association of diverse measures of social engagement with level of function in multiple cognitive domains in 838 persons without dementia who had a mean age of 80.2 (SD = 7.5). Social network size, frequency of social activity, and level of perceived social support were assessed in linear regression models adjusted for age, sex, education, and other covariates. Social activity and social support were related to better cognitive function, whereas social network size was not strongly related to global cognition. The results confirm that higher level of social engagement in old age is associated with better cognitive function but the association varies across domains of social engagement.

Loneliness and risk of Alzheimer disease.

CONTEXT: Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood. OBJECTIVE: To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD). DESIGN: Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up. PARTICIPANTS: A total of 823 older persons free of dementia at enrollment were recruited from senior citizen facilities in and around Chicago, Ill. Loneliness was assessed with a 5-item scale at baseline (mean +/- SD, 2.3 +/- 0.6) and annually thereafter. At death, a uniform postmortem examination of the brain was conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions. MAIN OUTCOME MEASURES: Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions. RESULTS: During follow-up, 76 subjects developed clinical AD. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile), and controlling for indicators of social isolation did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of AD. In 90 participants who died and in whom autopsy of the brain was performed, loneliness was unrelated to summary measures of AD pathology or to cerebral infarction. CONCLUSION: Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.