Background: Alzheimer disease (AD) is considered a leading cause of death, but few studies have examined the contribution of AD to mortality based on follow- up of representative US cohorts. Objective: To examine mort...Background: Alzheimer disease (AD) is considered a leading cause of death, but few studies have examined the contribution of AD to mortality based on follow- up of representative US cohorts. Objective: To examine mortality rates, duration of survival, causes of death, and the contribution of AD to the risk of mortali ty in an aging community-based cohort, controlling for other predictors. Design : Fifteen-year prospective epidemiological study. Mortality rates per 1000 pers on-years and the population-attributable risk of mortality were determined. Co x proportional hazards models were used to estimate relative risk of mortality d ue to AD, adjusting for relevant covariates. Death certificates were abstracted for listed causes of death. Setting: A largely blue-collar rural community in s outh-western Pennsylvania. Participants: A community-based cohort of 1670 adul ts 65 years and older at study enrollment. Main Outcome Measure: Mortality. Resu lts: In the overall cohort, AD was a significant predictor of mortality, with a hazard ratio of 1.4 after adjusting for covariates. The population-attributable risk of mortality from AD was 4.9%based on the same model. Examining the sexes separately, AD increased mortality risk only among women. Death certificates of AD subjects were more likely to list dementia/AD, other brain disorders, pneumo nia, and dehydration, and less likely to include cancer. Conclusions: Alzheimer disease was responsible for 4.9%of the deaths in this elderly cohort. Alzheimer disease increased the risk of mortality 40%in the cohort as a whole and separa tely in women but not in men. The mean (SD) duration of survival with AD was 5.9 (3.7) years, and longer with earlier age at onset.展开更多
Background: The microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau231) has been investigated as a potential marker of Alzh eimer disease. Levels of cerebrospinal fluid (CSF)p-tau231 v...Background: The microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau231) has been investigated as a potential marker of Alzh eimer disease. Levels of cerebrospinal fluid (CSF)p-tau231 vary across patients with Alzheimer disease. We hypothesized that these variations partially reflect differences in the degree of neuronal damage and therefore may be used to predi ct structural disease progression. Objective: To investigate whether CSF p-tau2 31 levels correlate with rates of hippocampal atrophy as an in vivo marker of re gional neuronal loss. Design and Patients: We measured hippocampal volumes on th e basis of serial magnetic resonance image exanimations in 22 patients with Alzh eimer disease. In addition, we determined CSF p-tau231 levels at baseline. Resu lts: Levels of CSF p-tau231 were significantly correlated with baseline hippoca mpal volumes (P < .001) and rates of hippocampal atrophy (left hippocampus, P < .001; right hippocampus, P=.02), independent of disease duration and severity. C onclusion: These findings suggest that variations in p-tau231 levels may be use d to predict progression of brain atrophy in patients with Alzheimer disease.展开更多
Background: To understand the earliest signs of cognitive decline caused by Alzheimer disease (AD) and other illnesses causing dementia, information is needed from well-characterized individuals without dementia studi...Background: To understand the earliest signs of cognitive decline caused by Alzheimer disease (AD) and other illnesses causing dementia, information is needed from well-characterized individuals without dementia studied longitudinally until autopsy. Objective: To determine clinical and cognitive features associated with the development of AD or other dementias in older adults. Design: Longitudinal study of memory and aging. Setting: Alzheimer’s Disease Research Center, St Louis, Mo. Main Outcome Measures: Clinical Dementia Rating, its sum of boxes, and neuropathologic diagnosis of dementia. Participants: Eighty control participants who eventually came to autopsy. Results: Individuals who did not develop dementia showed stable cognitive performance. Entry predictors of dementia were age, deficits in problem solving as well as memory, slowed psychomotor performance, and depressive features. Minimal cognitive decline occurred prior to dementia diagnosis, after which sharp decline was noted. Even individuals who were minimally cognitively impaired (Clinical Dementia Rating=0.5) typically had neuropathologic AD at autopsy. Histopathologic AD also was present in 34%of individuals who did not have dementia at death; these individuals without dementia showed an absence of practice effects on cognitive testing. Conclusions: Increased age, depressive features, and even minimal cognitive impairment, as determined clinically by Clinical Dementia Rating sum of boxes and by slowed psychomotor performance, identify older individuals with out dementia who develop dementia. Older adults who do not develop dementia ha ve stable cognitive performance. The absence of practice effects may denote the subset of older adults without dementia with histopathologic AD, which may refle ct a preclinical stage of the illness.展开更多
Background: Laboratory evidence of cholesterol-induced production of amyloid βas a putative neurotoxin precipitating Alzheimer disease, along with epidemiol ogical evidence, suggests that cholesterol-lowering statin ...Background: Laboratory evidence of cholesterol-induced production of amyloid βas a putative neurotoxin precipitating Alzheimer disease, along with epidemiol ogical evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. Objective: To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in pat ients with mild to moderate Alzheimer disease. Design: Pilot intention-to-trea t, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) tria l with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covarian ce as the primary method of statistical assessment. Participants: Individuals wi th mild to moderate Alzheimer disease (Mini-Mental State Examination score of 1 2-28) were recruited. Of the 98 participants providing informed consent, 71 wer e eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable. Main Outcome Measures: The primary outcome measures were change in Alzheimer’s Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale s cores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, a nd the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Invent ory. The tertiary outcome measures included total cholesterol, low-density lipo protein cholesterol, and very low-density lipoprotein cholesterol levels. Resul ts: Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This bene ficial effect reached significance for the Geriatric Depression Scale and the Al zheimer’s Disease Assessment Scale-cognitive subscale at 6 months and was sign ificant at the level of a trend for the Alzheimer’s Disease Assessment Scalec ognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. Conclusion: Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.展开更多
Background: Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in th is...Background: Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in th is population with those found in Anglo (white non-Latino) patients. Objective: To compare the age at AD symptom onset in Latino and Anglo individuals. Design: Cross-sectional assessment using standardized methods to collect and compare a ge at AD symptom onset, demographic variables, and medical variables. Setting: F ive National Institute on Aging-sponsored Alzheimer’s Disease Centers with exp erience evaluating Spanish-speaking individuals. Patients: We evaluated 119 Lat ino and 55 Anglo patients who had a diagnosis of AD. Main Outcome Measure: Age a t symptom onset. Results: After adjusting for center, sex, and years of educatio n, Latino patients had a mean age at symptom onset 6.8 years earlier (95%confid ence interval, 3.5-10.3 years earlier) than Anglo patients. Conclusions: An ear lier age at symptom onset suggests that US mainland Latino individuals may exper ience an increased burden of AD compared with Anglo individuals. The basis for t he younger age at symptom onset remains obscure.展开更多
文摘Background: Alzheimer disease (AD) is considered a leading cause of death, but few studies have examined the contribution of AD to mortality based on follow- up of representative US cohorts. Objective: To examine mortality rates, duration of survival, causes of death, and the contribution of AD to the risk of mortali ty in an aging community-based cohort, controlling for other predictors. Design : Fifteen-year prospective epidemiological study. Mortality rates per 1000 pers on-years and the population-attributable risk of mortality were determined. Co x proportional hazards models were used to estimate relative risk of mortality d ue to AD, adjusting for relevant covariates. Death certificates were abstracted for listed causes of death. Setting: A largely blue-collar rural community in s outh-western Pennsylvania. Participants: A community-based cohort of 1670 adul ts 65 years and older at study enrollment. Main Outcome Measure: Mortality. Resu lts: In the overall cohort, AD was a significant predictor of mortality, with a hazard ratio of 1.4 after adjusting for covariates. The population-attributable risk of mortality from AD was 4.9%based on the same model. Examining the sexes separately, AD increased mortality risk only among women. Death certificates of AD subjects were more likely to list dementia/AD, other brain disorders, pneumo nia, and dehydration, and less likely to include cancer. Conclusions: Alzheimer disease was responsible for 4.9%of the deaths in this elderly cohort. Alzheimer disease increased the risk of mortality 40%in the cohort as a whole and separa tely in women but not in men. The mean (SD) duration of survival with AD was 5.9 (3.7) years, and longer with earlier age at onset.
文摘Background: The microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau231) has been investigated as a potential marker of Alzh eimer disease. Levels of cerebrospinal fluid (CSF)p-tau231 vary across patients with Alzheimer disease. We hypothesized that these variations partially reflect differences in the degree of neuronal damage and therefore may be used to predi ct structural disease progression. Objective: To investigate whether CSF p-tau2 31 levels correlate with rates of hippocampal atrophy as an in vivo marker of re gional neuronal loss. Design and Patients: We measured hippocampal volumes on th e basis of serial magnetic resonance image exanimations in 22 patients with Alzh eimer disease. In addition, we determined CSF p-tau231 levels at baseline. Resu lts: Levels of CSF p-tau231 were significantly correlated with baseline hippoca mpal volumes (P < .001) and rates of hippocampal atrophy (left hippocampus, P < .001; right hippocampus, P=.02), independent of disease duration and severity. C onclusion: These findings suggest that variations in p-tau231 levels may be use d to predict progression of brain atrophy in patients with Alzheimer disease.
文摘Background: To understand the earliest signs of cognitive decline caused by Alzheimer disease (AD) and other illnesses causing dementia, information is needed from well-characterized individuals without dementia studied longitudinally until autopsy. Objective: To determine clinical and cognitive features associated with the development of AD or other dementias in older adults. Design: Longitudinal study of memory and aging. Setting: Alzheimer’s Disease Research Center, St Louis, Mo. Main Outcome Measures: Clinical Dementia Rating, its sum of boxes, and neuropathologic diagnosis of dementia. Participants: Eighty control participants who eventually came to autopsy. Results: Individuals who did not develop dementia showed stable cognitive performance. Entry predictors of dementia were age, deficits in problem solving as well as memory, slowed psychomotor performance, and depressive features. Minimal cognitive decline occurred prior to dementia diagnosis, after which sharp decline was noted. Even individuals who were minimally cognitively impaired (Clinical Dementia Rating=0.5) typically had neuropathologic AD at autopsy. Histopathologic AD also was present in 34%of individuals who did not have dementia at death; these individuals without dementia showed an absence of practice effects on cognitive testing. Conclusions: Increased age, depressive features, and even minimal cognitive impairment, as determined clinically by Clinical Dementia Rating sum of boxes and by slowed psychomotor performance, identify older individuals with out dementia who develop dementia. Older adults who do not develop dementia ha ve stable cognitive performance. The absence of practice effects may denote the subset of older adults without dementia with histopathologic AD, which may refle ct a preclinical stage of the illness.
文摘Background: Laboratory evidence of cholesterol-induced production of amyloid βas a putative neurotoxin precipitating Alzheimer disease, along with epidemiol ogical evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. Objective: To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in pat ients with mild to moderate Alzheimer disease. Design: Pilot intention-to-trea t, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) tria l with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covarian ce as the primary method of statistical assessment. Participants: Individuals wi th mild to moderate Alzheimer disease (Mini-Mental State Examination score of 1 2-28) were recruited. Of the 98 participants providing informed consent, 71 wer e eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable. Main Outcome Measures: The primary outcome measures were change in Alzheimer’s Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale s cores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, a nd the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Invent ory. The tertiary outcome measures included total cholesterol, low-density lipo protein cholesterol, and very low-density lipoprotein cholesterol levels. Resul ts: Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This bene ficial effect reached significance for the Geriatric Depression Scale and the Al zheimer’s Disease Assessment Scale-cognitive subscale at 6 months and was sign ificant at the level of a trend for the Alzheimer’s Disease Assessment Scalec ognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. Conclusion: Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.
文摘Background: Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in th is population with those found in Anglo (white non-Latino) patients. Objective: To compare the age at AD symptom onset in Latino and Anglo individuals. Design: Cross-sectional assessment using standardized methods to collect and compare a ge at AD symptom onset, demographic variables, and medical variables. Setting: F ive National Institute on Aging-sponsored Alzheimer’s Disease Centers with exp erience evaluating Spanish-speaking individuals. Patients: We evaluated 119 Lat ino and 55 Anglo patients who had a diagnosis of AD. Main Outcome Measure: Age a t symptom onset. Results: After adjusting for center, sex, and years of educatio n, Latino patients had a mean age at symptom onset 6.8 years earlier (95%confid ence interval, 3.5-10.3 years earlier) than Anglo patients. Conclusions: An ear lier age at symptom onset suggests that US mainland Latino individuals may exper ience an increased burden of AD compared with Anglo individuals. The basis for t he younger age at symptom onset remains obscure.
