Replication study of genome-wide associated SNPs with late-onset Alzheimer's disease.

Late-onset Alzheimer's disease (LOAD) is a multifactorial disease with the potential involvement of multiple genes. Four recent genome-wide association studies (GWAS) have found variants showing significant association with LOAD on chromosomes 6, 10, 11, 12, 14, 18, 19, and on the X chromosome. We examined a total of 12 significant SNPs from these studies to determine if the results could be replicated in an independent large case-control sample. We genotyped these 12 SNPs as well the E2/E3/E4 APOE polymorphisms in up to 993 Caucasian Americans with LOAD and up to 976 age-matched healthy Caucasian Americans. We found no statistically significant associations between the 12 SNPs and the risk of AD. Stratification by APOE*4 carrier status also failed to reveal statistically significant associations. Additional analyses were performed to examine potential associations between the 12 SNPs and age-at-onset (AAO) and disease duration among AD cases. Significant associations were observed between AAO and ZNF224/rs3746319 (P = 0.002) and KCNMA1/rs16934131 (P = 0.0066). KCNMA1/rs16934131 also demonstrated statistically significant association with disease duration (P = 0.0002). Although we have been unable to replicate the reported GWAS association with AD risk in our sample, we have identified two new associations with AAO and disease duration that need to be confirmed in additional studies.

Epidemiology for the clinical neurologist.

Epidemiology is a foundation of all clinical and public health research and practice. Epidemiology serves seven important uses for the advancement of medicine and public health. It enables community diagnosis by quantifying risk factors and diseases in the community; completes the clinical picture of disease by revealing the entire distribution of disease and presenting meaningful population averages from representative samples; identifies risk factors for disease by detecting and quantifying associations between exposures and disease and evaluating causal hypotheses; computes individual risk to identify high-risk groups to whom preventive interventions can be targeted; evaluates historic trends that monitor disease over time and provide clues to etiology; delineates new syndromes and disease subtypes not previously apparent in clinical settings, helping to streamline effective disease management; and investigates the effects of health services on population health to identify effective public health interventions. The clinician with a grasp of epidemiologic principles is in a position to critically evaluate the research literature, to apply it to clinical practice, and to undertake valid clinical epidemiology research with patients in clinical settings.

The temporal relationship between depressive symptoms and dementia: a community-based prospective study.

BACKGROUND: The temporal relationship between the appearance of depressive symptoms and the clinical onset of dementia and Alzheimer disease was evaluated in a community sample. METHODS: An original sample of 1366 subjects aged 65 years or older, selected randomly from a rural Pennsylvania community, was cognitively screened at study entry and every 2 years thereafter. A subset of 954 survivors of this cohort without dementia was screened for depressive symptoms at the second and subsequent data-collection waves. A "depression cluster" was identified by the presence of 5 or more depressive symptoms, including depressed mood, at the time of screening. Cognitively impaired subjects and a sample of unimpaired controls underwent standardized clinical evaluation to determine the presence of incident dementia (by DSM-III-R criteria) and probable or possible Alzheimer disease (by criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and to estimate the clinical onset of dementia symptoms. RESULTS: A highly increased probability of the depression cluster developing existed among subjects following the onset of dementia (15.4% [6/39]) and Alzheimer disease (17.6% [6/34]) compared with subjects without dementia (3.2% [23/712]). The odds ratios, after adjustment for age, sex, education level, and self reported memory loss, for the development of depression were 6.5 (95% confidence interval, 2.2-19.1) in subjects with Alzheimer disease and 5.2 (95% confidence interval, 1.8-15.2) in subjects with overall dementia. Depressive symptoms did not confer a significantly increased relative risk of dementia (1.27; 95% confidence interval, 0.55-2.93) or Alzheimer disease (1.28; 95% confidence interval, 0.51-3.20). CONCLUSION: Depressive symptoms appeared to be early manifestations, rather than predictors, of Alzheimer disease in this community sample.

Assessing depression in primary medical and psychiatric practices.

A two-stage assessment of newly admitted outpatients at community mental health centers and primary medical care centers found the Center for Epidemiological Studies Depression Scale to be highly sensitive but relatively nonspecific when compared with assessments of depression by the Diagnostic Interview Schedule. Considerably higher than usual screening scores are recommended with both patient populations to improve the efficiency of the Center for Epidemiological Studies Depression Scale. The reasons for our finding that primary care clinicians underdiagnose depressive disorder while psychiatric clinicians overdiagnose it relative to the Diagnostic Interview Schedule include varied presentations by each sector's patients, differing clinical acumen, and factors affecting third-party reimbursement.

Patterns of cognitive decline in presymptomatic Alzheimer disease: a prospective community study.

BACKGROUND: Specific patterns of decline over time were evaluated across a spectrum of cognitive measures in presymptomatic Alzheimer disease (AD) within a community sample. METHODS: A total of 551 individuals completed a battery of standard cognitive tests 3.5 and 1.5 years before outcome (clinical onset of AD vs continued nondemented status) within a prospective community-based study of AD. Test score changes in 68 cases (who subsequently developed symptomatic AD) and 483 controls (who remained nondemented) on each of 15 cognitive measures were transformed into z scores adjusted for age, sex, and education. A case-control rate ratio of the proportions of individuals who showed "cognitive decline" on each test was calculated, representing the relative magnitude of cognitive decline on each test in presymptomatic AD compared with normal aging. RESULTS: Declines in Trail-Making Tests A and B and Word List delayed recognition of originals and third immediate learning trial had the highest rate ratios, larger than 3.0 (P<.01). These were followed by Word List delayed recognition of foils and delayed recall, Consortium to Establish a Registry for Alzheimer's Disease Praxis, Clock Drawing, the Boston Naming Test, and Orientation, with rate ratios between 1.7 and 3.0 (P<.05). CONCLUSIONS: Memory and executive dysfunction showed the greatest decline over time in individuals who would clinically manifest AD 1.5 years later. These findings might help us understand the underlying evolution of the early neurodegenerative process. They highlight the importance of executive dysfunction early in the disease process and might facilitate early detection of AD.

Cardiac output and peripheral resistance in strains of rats sensitive and resistant to NaCl hypertension.

The interrelationship of blood pressure, cardiac output, and peripheral resistance was studied in Dahl "S" and "R" rats after 3 days on a high (8%) NaCl diet. Both "S" and "R" rats were normotensive when fed a normal (0.3%) NaCl diet. After 3 days of the high NaCl diet, the "R" rats remained normotensive (BP 112 mm Hg), while the "S" rats had an elevation of arterial pressure (BP 133 mm Hg) (p less than 0.001). The cardiac outputs of both "S" and "R" rats were similar on the low NaCl diet. After 3 days of high NaCl feeding, the cardiac output of the "R" rats rose 18% above the "R" control level (p less than 0.0001), while the peripheral resistance declined 14% below the "R" control level (p less than 0.005), and the blood pressure (BP) did not change, a pattern quite contrary to the concept of "whole-body" autoregulation. With a similar 3-day high NaCl feeding in "S" rats, cardiac output (p less than 0.005) and peripheral resistance (p less than 0.05) both increased 10%, while BP rose 20%. After 7 days of high NaCl feeding, the cardiac output of the "S" rats had returned to normal, while blood pressure and peripheral resistance both continued to be elevated. This pattern of response in "S" rats could be compatible with the concept of "whole-body" autoregulation. However, since both NaCl hypertension and Goldblatt hypertension can occur in settings in which "whole-body" autoregulation appears not be to causally related, one cannot be certain whether "whole-body" autoregulation is playing a causal role in the mechanism of NaCl-induced hypertension in "S" rats. It is a striking dichotomy that 3 days of high salt feeding produces vasoconstriction in "S" rats and vasodilation in "R" rats.

High potassium diets protect against dysfunction of endothelial cells in stroke-prone spontaneously hypertensive rats.

Two lines of evidence strongly support the hypothesis that high potassium diets protect arterial endothelial cells from hypertensive damage. Stroke-prone spontaneously hypertensive rats (SHRSP) fed normal (0.75%) K or high (2.1%) K and normotensive Wistar-Kyoto rats (WKY) were examined in an endothelial function study and a histological study. In the endothelial function study, aortic rings were suspended in tissue baths to monitor isometric tension. Rings contracted with norepinephrine were tested with acetylcholine and sodium nitroprusside. In normal K SHRSP (blood pressure, 156 mm Hg), endothelium-dependent acetylcholine relaxation was severely depressed by 49% (p less than 0.001), whereas in high K SHRSP (blood pressure, 155 mm Hg), normal values were preserved. Endothelium-independent nitroprusside relaxation was virtually the same in both the SHRSP groups (high K vs normal K diet). Since indomethacin did not improve the impaired acetylcholine relaxation in normal K SHRSP, the cyclooxygenase products do not appear to have affected the endothelium-dependent relaxation in the normal K SHRSP. Thus, the endothelium-dependent relaxation response was much decreased in the normal K SHRSP and was preserved in the high K SHRSP. Thus, a high K diet appears to protect the aortic endothelium from a hypertension-induced dysfunction. In the histological study, aortic and mesenteric intimal lesions were assessed blindly under the microscope and graded from 0 to 60 for aortic and from 0 to 40 for mesenteric lesions. Aortic intimal lesion scores were 28 in normal K SHRSP (blood pressure, 209 mm Hg) and 13 in high K SHRSP (blood pressure, 207 mm Hg; -54%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Dahl S rats have increased natriuretic factor in atria but are markedly hyporesponsive to it.

Three experiments were carried out to determine whether atrial natriuretic factor (ANF) plays a part in Dahl hypertension. Results showed that ANF from both atria from 13 Dahl salt-sensitive (S) rats that had been fed a 4% NaCl diet for 12 weeks induced an average peak Na excretion of 23.0 muEq/min/g kidney in 13 Sprague-Dawley (SD) recipients vs 12.6 from atria from 13 salt-resistant (R) rats fed 4% NaCl (-45%, p less than 0.01), possibly indicating greater ANF secretion in S rats in order to enhance a reduced Na excretion. In 13 R rats, the ANF content in both atria increased from 14.0 after a 0.11% NaCl diet to 23.7 after 5 days of 4% NaCl diet (p less than 0.001) and then back to 12.6 after 12 weeks of 4% NaCl (p less than 0.001). Thus, ANF almost doubled after brief Na loading but returned to normal during continued Na loading. In S rats with a tendency to Na retention, ANF was elevated to about 23 in all three periods. ANF produced a 130-fold increase in natriuresis and a renal papillary plasma flow ( RPPF ) of 30.8 ml/min/100 g, 41% above the control level of 21.7, p less than 0.001. The marked increase in RPPF is very likely a partial cause of the natriuresis. A constant amount of ANF was continuously infused intravenously into 10 S rats and nine R rats all on 0.11% NaCl diets. Mean Na excretions in R and S were 5.3 and 4.6 muEq/min/100 g kidney before ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Potassium protection against lesions of the renal tubules, arteries, and glomeruli and nephron loss in salt-loaded hypertensive Dahl S rats.

Dahl S rats (20/group) were given three Purina diets for 24 weeks: 4% NaCl-no added potassium (BP 171 mm Hg); 4% NaCl-3.8% K citrate (BP 174 mm Hg); 4% NaCl-2.6% KCl (BP 173 mm Hg). The added potassium did not lower blood pressure (BP) but strikingly reduced microscopic renal lesions. Focal tubular dilation was scored blindly (100, severest lesions; 0, normal). Scores were: renal cortex: no potassium (41); K citrate (20); KCl (22), 50% improvement p less than 0.001; outer medulla: no potassium (79); K citrate (54); KCl (58), 30% improvement p less than 0.001; renal papilla: no potassium (49); K citrate (28); KCl (28), 43% improvement, p less than 0.001. Both K citrate and KCl also eliminated the thickened walls and relatively narrowed lumens of the hypertensive renal arterioles, without lowering BP. In these same rats, the wall thickness of arterioles from 20 normotensive salt-resistant (R) rats on 4% NaCl averaged 18.9 mu vs 26.1 mu in arterioles from 18 hypertensive salt-sensitive (S) rats on 4% NaCl with no added potassium. Adding either KCl or K citrate to the 4% NaCl diet strikingly reduced the wall thickness to that found in the R rat, even though the BP was not reduced at all. Potassium did not lower the high BP but apparently reduced the severity of the arteriolar lesions resulting from that high BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Association between dementia and elevated TSH: a community-based study.

We report on 194 individuals (96 men and 98 women), aged 65 and over, who had dementia assessments and basal TSH measurements as part of an ongoing epidemiological study of dementing disorders in a larger population. Dementia was diagnosed according to DSM-III-R and measured by the Clinical Dementia Rating scale; CDR scores of 0, 0.5, and > or = 1, represent individuals with no dementia (n = 122), possible dementia (n = 29), and definite dementia (n = 43), respectively. The odds ratio for the association of elevated TSH with definite dementia (CDR > or = 1) was 3.8 (95% confidence interval = 1.6, 9.1) and with possible and/or definite dementia (CDR > or = 0.5) was 3.8 (95% confidence interval = 1.6, 9.2), after adjusting for the effects of age, gender, and level of education. This is the first community-based study to report an association between TSH elevation and dementia. Our findings are consistent with recent evidence that subclinical hypothyroidism is associated with cognitive impairment, and that thyroidal state may influence cerebral metabolism.

Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study.

BACKGROUND: The APOE*E4 allele of the gene for apolipoprotein E (APOE) has been reported as a risk factor for Alzheimer disease (AD) to varying degrees in different ethnic groups. OBJECTIVE: To compare APOE*E4-AD epidemiological associations in India and the United States in a cross-national epidemiological study. DESIGN: Case-control design within 2 cohort studies, using standardized cognitive screening and clinical evaluation to identify AD and other dementias and polymerase chain reaction to identify APOE genotyping. PARTICIPANTS: Rural community samples, aged 55 years or older (n=4450) in Ballabgarh, India, and 70 years or older (n=886) in the Monongahela Valley region of southwestern Pennsylvania. MAIN OUTCOME MEASURES: Criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable and possible AD and Clinical Dementia Rating (CDR) scale for dementia staging. RESULTS: Frequency of APOE*E4 was significantly lower (P<.001) in Ballabgarh vs the Monongahela Valley (0.07 vs 0.11). Frequency of probable or possible AD, with CDR of at least 1.0, in the Indian vs US samples, was as follows: aged 55 to 69 years, 0.1% (Indian sample only); aged 70 to 79 years, 0.7% vs 3.1%; aged 80 years or older, 4.0% vs 15.7%. Among those aged 70 years or older, adjusted odds ratios (95% confidence interval) for AD among carriers of APOE*E4 vs noncarriers were 3.4 (1.2-9.3) and 2.3 (1.3-4.0) in the Indian and US samples, respectively, and not significantly different between cohorts (P=. 20). CONCLUSION: This first report of APOE*E4 and AD from the Indian subcontinent shows very low prevalence of AD in Ballabgarh, India, but association of APOE*E4 with AD at similar strength in Indian and US samples. Arch Neurol. 2000.

Cognitive tests that best discriminate between presymptomatic AD and those who remain nondemented.

OBJECTIVE: To identify the most accurate cognitive measures in discriminating between individuals with presymptomatic AD and individuals who remained nondemented. METHODS: During a 10-year prospective community study, 120 nondemented subjects completed a battery of standard cognitive tests and clinically manifested AD 1.5 years later. Performance on each of 16 cognitive tests was compared between these 120 presymptomatic cases and 483 controls who remained nondemented over the 10-year follow-up period. The area under the receiver operating characteristic (AUC) curve for each test was used to measure its accuracy of discrimination between cases and controls. RESULTS: Among the 16 neuropsychological tests, Word List Delayed Recall discriminated best between cases and controls (AUC = 0.806), followed by the Word List 3rd Learning Trial (0.787), Word List 1st Learning Trial (0.774), and Trail-making Test B (0.773), compared to the Mini-Mental State Examination (MMSE) (0.726). Both Word List Delayed Recall and Word List 3rd Learning Trial were significantly more accurate than the MMSE. The combination of Word List Delayed Recall and Trail-making Test B comprised the optimal set of cognitive measures, with the highest AUC (0.852). CONCLUSION: Measures of delayed recall and executive functions were the best discriminators between those who would manifest AD 1.5 years later and those who would remain nondemented. These findings are relevant for the early detection of AD and, therefore, for prevention and early intervention trials. Executive dysfunction may be a subtle manifestation of incipient AD, along with memory dysfunction.

Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project.

OBJECTIVE: To determine incidence rates by age, sex, and education of overall dementia and probable/ possible AD in a largely rural community. METHODS: Ten-year prospective study of a randomly selected community sample aged 65+; biennial cognitive screening followed by standardized clinical evaluation. Incidence rates were estimated for overall dementia (Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised, criteria and Clinical Dementia Rating [CDR]) and for probable/possible AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). RESULTS: The cohort consisted of 1,298 individuals free of dementia at study entry. Among these, 199 incident (new) cases of overall (all-cause) dementia with CDR stage > or = 0.5, including 110 with CDR > or = 1, were detected during follow-up. Among the incident cases, 153 (76.9%) had probable/ possible AD. Age-specific incidence rates are reported for all dementia and for probable/possible AD, by sex and CDR stage. Among all-cause dementias with CDR = 0.5, controlling for age and education, men had a higher incidence rate than women. In the same group, those with less than high school education had significantly higher incidence rates than those with more education. Rates did not vary significantly by sex or education for probable/possible AD or for dementia with CDR > or = 1. CONCLUSIONS: Incidence rates of all dementias and of AD increased with age; men and those with lesser education had higher rates of possible/incipient dementia (CDR = 0.5) in this community. Potential explanations for these sex and education effects are discussed.

Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study.

OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.

Small head size is related to low Mini-Mental State Examination scores in a community sample of nondemented older adults.

The objective of this analysis was to determine the relationship, if any, of head size to performance on a cognitive screening test among elderly nondemented adults participating in a community-based survey. The study sample included 825 subjects (533 women, 292 men), age 70 to 95 years. Multivariate analyses, with adjustment for age and education, revealed that smaller head size was associated with low Mini-Mental State Examination (MMSE) scores (i.e., below the 10th percentile) in both men and women. For every 1-centimeter increment in head size, there was a corresponding reduction of approximately 20% in the probability of a low MMSE score.

Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. BACKGROUND: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. METHODS: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. RESULTS: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. RECOMMENDATIONS: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.

Incidence of Alzheimer's disease in a rural community in India: the Indo-US study.

OBJECTIVE: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person-years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged > or =65 years was 4.7 per 1000 person-years, substantially lower than the corresponding rate of 17.5 per 1000 person-years in the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.

Epidemiology and diagnosis of depression in late life.

Depression is a significant concern in elderly patients. Reported prevalence rates differ greatly depending on the definition of depression and the population of interest, with increases reported in settings where comorbid physical illnesses are more common. In community-dwelling elderly patients, prevalences of depressive symptoms and major depressive disorder are 15% and 1% to 3%, respectively. Factors associated with depression in the elderly include female gender, alcohol and substance abuse, pharmaceuticals, family history, and medical conditions such as stroke, Alzheimer's disease, cancer, and heart disease. Recognition of depression is complex because patients often deny their depression, present with somatic complaints, or may have comorbid anxiety or cognitive impairment. Depression is underrecognized and undertreated in the elderly, despite evidence that the benefits of treatment outweigh potential risks.

Reporting of dementia on death certificates: a community study.

OBJECTIVE: To determine the extent to which conditions suggesting dementia are reported on death certificates of older adults and to identify the factors associated with reporting of dementia. DESIGN: A prospective epidemiological study in which community-dwelling subjects with and without dementia were identified and followed until death, after which their death certificates were examined. POPULATION: A total of 527 individuals who died during 8 years of follow-up of a population-based cohort of 1422 persons aged 65 and older at study entry. MEASUREMENTS: Demographic; study diagnoses, including Clinical Dementia Rating (CDR) Scale stages and diagnoses of Probable and Possible Alzheimer's disease (AD) by NINCDS-ADRDA criteria; disorders listed on death certificates as immediate, underlying, or contributory causes of death. RESULTS: Of 172 deceased subjects with study diagnoses of dementia, 30.2% had CDR = .5 and 69.8% had CDR > or = 1. Of 168 subjects in which dementia subtype could be diagnosed, Probable AD was diagnosed in 31.0% and Possible AD in 38.7%. On their death certificates, conditions indicating or suggesting dementia were reported in 23.8% of dementias overall; in 1.9% of those with CDR = .5 and 33.3% of those with CDR > or = 1; in 36.5% of those with Probable AD and 21.5% of those with Possible AD. In a multiple logistic regression model, variables associated independently with the reporting of dementia in demented individuals were: higher CDR stage of dementia (odds ratio (OR) 22.6; 95% confidence interval (CI), 2.9-174.7); likely etiology of dementia, Probable AD (OR = 3.5; CI, 1.1-10.6); and place of death, long-term care institution (OR = 3.8; 95% CI, 1.6-9.0). CONCLUSIONS: Although Alzheimer's disease is widely regarded as a leading cause of death, dementias are reported on the death certificates of only a quarter of demented individuals in the population at large. Reporting is more likely in those with more advanced dementia, with Probable Alzheimer's disease, and those who die in long-term care institutions.

Depression and disability associated with impaired vision: the MoVies Project.

OBJECTIVE: To assess how depression and impaired vision relate to disability in older people. DESIGN: An epidemiological survey of an age-stratified random community sample. SETTING: The rural mid-Monongahela Valley in South-western Pennsylvania. PARTICIPANTS: A total of 872 noninstitutionalized persons aged 68 and older, fluent in English, and with at least a grade 6 education. MEASUREMENTS: Demographics, self-reported vision impairment, OARS Instrumental Activities of Daily Living (IADL), and modified Center for Epidemiologic Studies-Depression scale to assess depression. RESULTS: Compared with subjects with intact vision, those with impaired vision were more likely to have five or more depressive symptoms (29.7% vs 8.5%; OR = 4.6, 95% CI = 2.2, 9.6) and to be more functionally impaired (OR = 9.7, 95% CI = 4.9, 19.2). The number of depressive symptoms (1-4: OR = 2.4, CI = 1.8, 3.4) and (5+: OR = 5.9, CI = 3.6, 9.8) was associated independently with IADL impairment after controlling for vision, age, and gender. CONCLUSIONS: Impaired vision and depression are both associated strongly with functional impairment in this community population of older adults. Depression, however, increases the odds of functional impairment independent of vision impairment. Treating depression may reduce excess disability associated with impaired vision.