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PubMed2000

Depression and risk of cognitive decline and Alzheimer's disease. Results of two prospective community-based studies in The Netherlands.

BACKGROUND: Depression may be associated with cognitive decline in elderly people with impaired cognition. AIMS: To investigate whether depressed elderly people with normal cognition are at increased risk of cognitive decline and Alzheimer's disease. METHODS: Two independent samples of older people with normal cognition were selected from the community-based Amsterdam Study of the Elderly (AMSTEL) and the Longitudinal Aging Study Amsterdam (LASA). In AMSTEL, depression was assessed by means of the Geriatric Mental State Schedule. Clinical diagnoses of incident Alzheimer's disease were made using a two-step procedure. In LASA, depression was assessed with the Center for Epidemiologic Studies Depression Scale. Cognitive decline was defined as a drop of > or = 3 on the Mini-Mental State Examination at follow-up. RESULTS: Both in the AMSTEL and the LASA sample, depression was associated with an increased risk of Alzheimer's disease and cognitive decline, respectively, but only in subjects with higher levels of education. CONCLUSIONS: In a subgroup of more highly educated elderly people, depression may be an early manifestation of Alzheimer's disease before cognitive symptoms become apparent.

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PubMed2003

Cross-linked fibrin degradation products (D-dimer), plasma cytokines, and cognitive decline in community-dwelling elderly persons.

OBJECTIVES: To investigate the effect of coagulation and inflammatory pathway activation on future cognitive decline in older persons. DESIGN: Prospective cohort study. SETTING: Rural and urban communities in North Carolina. PARTICIPANTS: Community-dwelling older people enrolled in the Duke Established Populations for Epidemiologic Studies of the Elderly in 1986. MEASUREMENTS: In 1992, blood was drawn for assay of D-dimer (1,723 subjects), Interleukin-6 (1,726 subjects), and other cytokines (1,551 subjects). Cognitive and functional assessments were performed in 1986, 1989, 1992, and 1996. Cognition was measured using the Short Portable Mental Status Questionnaire. RESULTS: Cognitive decline over a 4-year period was significantly correlated (P<.001) with D-dimer, age, race, and physical performance status as measured using the Rosow-Breslau and Nagi instruments. After controlling for demographics, functional status, and comorbidities, D-dimer remained predictive of cognitive decline. Proinflammatory cytokines were not associated with current cognitive status in cross-sectional analyses or with incident cognitive decline in prospective analyses. CONCLUSION: In a large sample of community-dwelling elders, higher levels of D-dimer were predictive of cognitive decline over a 4-year period. No clinically significant associations were found between age-related peripheral cytokine dysregulation and cognition.

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PubMed2005

Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging.

BACKGROUND: High stress hormone levels are associated with increased risk of cognitive decline in elderly individuals. However, the effect of late-life changes in stress hormone levels on cognitive decline risk has not been examined. Our objective was to investigate whether increase over time in urinary epinephrine excretion in older adults was associated with subsequent cognitive decline. METHODS: Measurements were made on 154 high-functioning men and women, 70-79 years of age, in 1988, 1991, and 1995. Twelve-hour overnight urinary excretion of epinephrine (normalized by creatinine excretion to adjust for body size) was recorded in 1988 and 1991. Cognitive functioning was assessed in 1991 and 1995 by summary scores based on standard tests of language, memory, abstraction, spatial recognition, and spatial construction. RESULTS: Compared to individuals whose epinephrine excretion decreased between 1988 and 1991, the individuals whose epinephrine excretion increased over the same period had greater subsequent declines in summary cognitive scores between 1991 and 1995. After adjusting for baseline epinephrine, baseline cognitive function, and relevant covariates, and stratifying by gender, increases in urine epinephrine were positively associated with cognitive decline only in men. CONCLUSIONS: We conclude that increase in urinary excretion of epinephrine predicts subsequent cognitive decline in older men.

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PubMed2000

Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.

OBJECTIVE: APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline. METHOD: - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening. RESULTS: A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke. CONCLUSIONS: Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.

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PubMed2006

Reported alcohol consumption and cognitive decline: The northern Manhattan study.

BACKGROUND: Moderate alcohol intake may slow cognitive decline, and both vascular and neurodegenerative mechanisms have been implicated. METHODS: We examined reported alcohol intake and cognitive decline in a community-based cohort of Hispanic, black and white individuals (n = 1,428). The role of the apolipoprotein E epsilon4 (APOE4) allele as a modifier was also studied. RESULTS AND CONCLUSIONS: Reported drinking was as follows: 300 participants (21%) were 'never' drinkers, 622 (44%) 'past' drinkers, 145 (10%) reported taking less than 1 drink weekly, 330 (23%) 1 drink weekly up to 2 daily and 31 (2%) more than 2 drinks daily. A positive relationship was seen between reported alcohol intake and cognition. Drinking less than 1 drink a week (p = 0.09), between 1 drink weekly up to 2 drinks daily (p = 0.001) and more than 2 drinks daily (p = 0.003) were associated with less cognitive decline on the modified Telephone Interview for Cognitive Status compared to never drinkers. This dose-response relationship was not modified by the presence of an APOE4 allele in a subsample.

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PubMed2005

Physical activity, cognitive activity, and cognitive decline in a biracial community population.

BACKGROUND: Findings from studies investigating whether physical activity reduces the risk of cognitive decline in old age have been inconsistent. OBJECTIVE: To examine whether participation in physical activity by older adults reduces the rate of cognitive decline after accounting for participation in cognitively stimulating activities. DESIGN: A prospective population study conducted from August 1993 to January 2003, with an average follow-up of 6.4 years. SETTING: A biracial community population on the south side of Chicago. PARTICIPANTS: Participants were 4055 community-dwelling adults 65 years and older who were able to walk across a small room and had participated in at least 2 of the 3 follow-up assessments. MAIN OUTCOME MEASURE: Annual rate of cognitive change as measured by a global cognitive score, which consisted of averaged standardized scores from 4 cognitive tests. RESULTS: In a mixed model adjusted for age, sex, race, and education, each additional physical activity hour per week was associated with a slower rate of cognitive decline by 0.0007 U/y (P = .04). However, with further adjustments (1) for participation in cognitive activities (beta = .0006, P = .10), (2) for depression and vascular diseases (beta = .0005, P = .19), and (3) by excluding participants whose global cognitive score at baseline was at or below the 10th percentile (beta = .0002, P = .45), the coefficients were smaller and no longer statistically significant. CONCLUSION: These data do not support the hypothesis that physical activity alone protects against cognitive decline among older adults.

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PubMed2006

A population-based study of the association between coronary artery bypass graft surgery (CABG) and cognitive decline: the Cache County study.

BACKGROUND: The relationship between coronary artery bypass graft (CABG) surgery and cognitive decline remains uncertain, in particular with regard to whether there is delayed cognitive decline associated with this procedure. METHODS: This was a population-based cohort study involving participants in the Cache County Study of Memory Health and Aging. At baseline the study enrolled 5,092 persons age 65 and older and followed them up three years later and again four years after that. Individuals who reported having undergone CABG surgery at study baseline or had this surgery in between follow-up waves were compared to individuals who never reported having the surgery. The main outcome measure was the Modified Mini Mental State (3MS). Multilevel models were used to examine the relationship between CABG surgery and cognitive decline over time. RESULTS: Study participants who had CABG surgery evidenced 0.95 points of greater decline relative to baseline on the 3MS at the first follow-up interview after CABG, and an average of 1.9 points of greater decline at the second follow-up interview, than those without CABG (t = -2.51, df = 2,316, p = 0.0121), after adjusting for several covariates, including number of vascular conditions. This decline was restricted to individuals who were more than five years past the procedure and was not evident in the early years after the surgery. CONCLUSIONS: CABG surgery is associated with accelerated cognitive decline more than five years after the procedure in a long-lived population. This decline is small and its clinical significance is uncertain. We could not find an association between CABG and decline in the first five post-operative years.

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PubMed2000

Sequence of cognitive decline in dementia in adults with Down's syndrome.

Adults with Down's syndrome (DS) are known to be at risk of dementia of the Alzheimer type (DAT), but because of their lifelong intellectual deficits, it is difficult to determine the earliest signs and characteristics of age-associated decline and dementia. In a longitudinal study in which all participants were healthy at the time of their entry into the study, the present authors compared the amount of decline on the subtests of the WISC-R to determine the sequence of cognitive decline associated with varying stages of dementia. Twenty-two individuals with varying degrees of cognitive decline were compared to 44 adults with DS who have remained healthy. All participants functioned in the mild or moderate range of intellectual disability at initial testing. On each subtest of the WISC-R, the amount of change experienced by the healthy participants over the study period was compared to the amount of change found for each of the groups with decline. Out of the individuals who showed declines, 10 adults with DS were classified as having 'questionable' decline based on the presence of memory impairment, and five and seven adults with DS were classified as in the 'early stage' and 'middle stage' of DAT, respectively, based on the presence of memory impairment, score on the Dementia Scale for Down Syndrome and a physician's diagnosis. It was found that participants who were identified as 'questionable', in addition to the memory loss that determined their classification, also showed significant declines on the Block Design and Coding subtests. The five adults in the early stage of dementia showed declines on these subtests, and in addition, on the Object Assembly, Picture Completion, Arithmetic and Comprehension subtests. The seven adults in the middle stage of dementia showed declines on these subtests, plus declines on Information, Vocabulary and Digit Span subtests. The Picture Arrangement and Similarities subtests were not useful in distinguishing between the groups because of baseline floor effects for a substantial proportion of participants. The present longitudinal study showed a sequence of cognitive decline associated with DAT, beginning with a possible 'pre-clinical' stage, and progressing through the early and middle stages. This approach begins to define the sequence of declining cognitive capacities that contributes to the observed functional deterioration caused by Alzheimer's disease and that is likely to reflect the involvement of cortical areas as the disease progresses.

Adult↗

PubMed2006

Vascular risk factors and cognitive decline among elderly male twins.

BACKGROUND: Studies investigating the association between cardiovascular risk factors and cognitive decline report discrepant outcomes. The co-twin control method improves on traditional case-control approaches by controlling for within-twin pair similarities of genetic and early environmental influences. OBJECTIVE: To examine the association of diabetes, hypertension, hypercholesterolemia, and elevated body mass index (BMI) (>30 kg/m(2)), individually and combined, with cognitive decline over a 12-year period in members of the National Academy of Sciences-National Research Council Twin Registry of World War II male veterans. METHODS: Modified Telephone Interview for Cognitive Status (TICS-m) was administered four times at approximately 4-year intervals from 1990 to 2002 as part of an epidemiologic study of dementia. Self-report medical information was collected from 1996 to 2002. We examined the difference in cognitive decline within twin pairs discordant for the vascular risk factors while controlling for baseline TICS-m, education, smoking, and alcohol history. RESULTS: Among twin pairs discordant for diabetes (n = 177), the diabetic twins declined an average of almost 1 point more than their nondiabetic co-twins (p = 0.018) at the last screening time point. Further analyses showed that this was in large part due to greater decline among older men (age 76 to 84 years). Cognitive change was not significantly different between members of pairs discordant for hypertension (n = 326), hypercholesterolemia (n = 282), or elevated BMI (n = 166). CONCLUSION: Based on this study of twin pairs who share similar genetic and early environmental risks for cardiovascular risk factors, diabetes is associated with greater cognitive decline, particularly among the oldest individuals.

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PubMed2006

The influence of latent viral infection on rate of cognitive decline over 4 years.

OBJECTIVES: To examine whether cytomegalovirus (CMV) and herpes simplex virus type-1 (HSV-1) are associated with cognitive decline over a 4-year period and to assess whether C-reactive protein (CRP) modifies these relationships. DESIGN: Prospective cohort study over a 4-year period. SETTING: Community-dwelling elderly population. PARTICIPANTS: The sample was a subset (1,204/1,789) of participants in the Sacramento Area Latino Study on Aging (SALSA) aged 60 to 100. MEASUREMENTS: Participants were screened annually over a 4-year period for cognitive function and episodic memory. Cognitive function was assessed using the modified Mini-Mental State Examination, and episodic memory was assessed using a word list-learning test of delayed recall. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV-1 and for levels of CRP. RESULTS: There was a significantly higher rate of cognitive decline over the 4-year period in subjects with the highest CMV antibody levels at baseline than in individuals with the lowest levels (beta=-0.053, standard error =0.018; P=.003), after controlling for age, sex, education, income, and chronic health conditions. There was no association between HSV-1 antibody levels and cognitive decline. CRP did not modify the relationship between viral antibody levels and cognitive decline. CONCLUSION: This is the first study to show that individuals with higher levels of antibody to CMV experience a more-rapid rate of cognitive decline than those with lower levels. Understanding the mechanisms by which CMV influences cognition may aid development of intervention strategies targeting infection, viral reactivation, and immune response over the life course.

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PubMed2004

Do severity and duration of depressive symptoms predict cognitive decline in older persons? Results of the Longitudinal Aging Study Amsterdam.

BACKGROUND AND AIMS: Some prospective studies show that depression is a risk factor for cognitive decline. So far, the explanation for the background of this association has remained unclear. The present study investigated 1) whether depression is etiologically linked to cognitive decline; 2) whether depression and cognitive decline may be the consequence of the same underlying subcortical pathology, or 3) whether depression is a reaction to global cognitive deterioration. METHODS: A cohort of 133 depressed and 144 non-depressed older persons was followed at eight successive observations over 3 years. All subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). Depression symptoms were measured by means of the CES-D at eight successive waves. Cognitive function (memory function, information processing speed, global cognitive functioning) was assessed at baseline and at the last CES-D measurement. RESULTS: The severity and duration of depressive symptoms were not associated with subsequent decline in memory functioning or global cognitive decline. There was an association between both chronic mild depression and chronic depression, and decline in speed of information processing. CONCLUSIONS: These results support the hypothesis that, in older persons, chronic depression as well as cognitive decline may be the consequence of the same underlying subcortical pathology.

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PubMed2004

Depressive symptoms and cognitive decline in a community population of older persons.

BACKGROUND: An association between depressive symptoms and cognitive decline has been observed in selected cohorts of older people, but studies of defined populations have had conflicting results. OBJECTIVE: To test whether the level of depressive symptoms predicted the rate of cognitive decline in a biracial community of older persons. METHODS: 4392 older people (88% of those eligible) from a defined community in Chicago completed two or three structured interviews at approximately three year intervals for an average of 5.3 years. At the baseline interview, the number of depressive symptoms was assessed with a 10 item version of the Center for Epidemiologic Studies Depression scale. Cognitive function was assessed at each interview with four performance tests, from which a previously established measure of global cognition was derived. Random effects models were used to assess change in cognition and its relation to depressive symptoms, controlling for age, sex, race, education, and baseline cognitive function. RESULTS: Participants reported a median of one depressive symptom at baseline (interquartile range, 0 to 2). For each depressive symptom, the rate of cognitive decline increased by a mean of about 5%. Results were not substantially changed when persons with cognitive impairment at baseline were excluded, or when chronic illness or participation in cognitively stimulating activities was controlled, and the association was not modified by age, sex, race, or education. CONCLUSIONS: The results suggest that depressive symptoms predict cognitive decline in old age.

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PubMed2005

Diabetes, aging, and cognitive decline.

Type 1 diabetes is associated with cognitive changes in children and adults, but the extent to which cognition declines with increasing age, and increasing duration of diabetes, remains poorly understood. This cross-sectional study assessed neuropsychological performance on 200 diabetic and 175 nondiabetic adults, 18-64 years of age, stratified into five age bands. Similar age-related cognitive declines were seen on measures of problem-solving, learning and memory, and psychomotor speed, but it was only on the latter measure that diabetic and nondiabetic subjects differed significantly. The best predictor of psychomotor slowing was the presence of clinically significant biomedical complications, particularly proliferative retinopathy, peripheral neuropathy, and peripheral vascular disease (PVD). It now appears that psychomotor slowing is the fundamental cognitive deficit associated with diabetes mellitus; why other cognitive skills are relatively unaffected remains poorly understood.

Adolescent↗

PubMed1999

Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging.

OBJECTIVE: To examine whether baseline high blood pressure and antihypertensive treatment predicts cognitive decline in elderly individuals. METHODS: A longitudinal population-based study of elderly individuals (n = 1,373) in Nantes (western France) was undertaken. Individuals 59 to 71 years of age were selected from electoral rolls. High blood pressure at baseline was defined as systolic blood pressure > or =160 mm Hg or diastolic blood pressure > or =95 mm Hg. Cognitive decline was defined as a drop of 4 points or more on the Mini-Mental State Examination between baseline and the 4-year assessment. RESULTS: There is an association between high blood pressure at baseline and cognitive decline at the 4-year assessment (odds ratio, 2.8; 95% CI, 1.6 to 5.0). In participants with high blood pressure, the risk of cognitive decline was 4.3 (95% CI, 2.1 to 8.8) in those without antihypertensive therapy and 1.9 (95% CI, 0.8 to 4.4) in those being treated. In participants with high blood pressure both at baseline and at the 2-year assessment, the risk for untreated participants was 6.0 (95% CI, 2.4 to 15.0) compared with 1.3 (95% CI, 0.3 to 4.9) in treated participants. CONCLUSIONS: High blood pressure was associated with cognitive decline. In individuals with high blood pressure, cognitive decline occurred in a relatively short time period and the risk was highest in untreated hypertensive patients.

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PubMed2006

Cognitive decline and survival in Alzheimer's disease.

OBJECTIVE: To test the association of rate of cognitive decline, an indicator of the severity of the underlying disease process, with risk of death in Alzheimer's disease (AD). METHODS: A total of 472 persons with clinically diagnosed AD were recruited from a memory disorders clinic and day care centers in the Chicago area. They completed a uniform clinical evaluation at baseline and a battery of nine cognitive tests at six-month intervals for a mean of about three years. A previously established measure of global cognition was derived from the nine tests. RESULTS: During follow-up, 168 persons (36%) died. In a proportional hazards model that controlled for age, sex, race, education, and baseline level of cognition, individual rate of global cognitive decline, estimated with least squares regression, was linearly related to mortality risk. Thus, a person declining minimally (increase of 0.04 unit per year, 90th percentile) was 2.7 times less likely to die during the study period than a person declining rapidly (decrease of 0.76 unit per year, 10th percentile). Controlling for baseline disability did not substantially affect results. The association of cognitive decline with mortality was substantially stronger for white persons compared to African Americans and in those with less compared to more education. CONCLUSION: The results indicate that the rate at which cognition declines in AD is robustly related to survival.

Adult↗

PubMed2005

APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model.

BACKGROUND: The APOE genotype predicts the age at onset of Alzheimer disease (AD) and neuropathologic progression. However, studies relating APOE alleles to the rate of cognitive decline have been inconclusive. This may stem from their use of linear statistical analyses. OBJECTIVE: To model relations of APOE alleles to the rate of cognitive decline in AD, nonlinearly. METHODS: Serial measures of cognitive ability were obtained using the cognitive scale of the Cambridge Examination for Mental Disorders of the Elderly in 218 patients with AD. The relations of these serial scores to APOE alleles were tested using nonlinear and linear mixed-effects models. RESULTS: In the non-linear model, possession of an APOE epsilon4 allele related to earlier and faster cognitive decline, but possession of an APOE epsilon2 related to slower decline. Patients homozygous for APOE epsilon4 showed faster cognitive decline than heterozygotes. The linear model was less sensitive and did not detect differences between APOE epsilon4 homo- and heterozygotes. CONCLUSIONS: APOE genotype strongly predicts the rate of cognitive decline in Alzheimer disease. The decline shows a dose-response relation with the APOE epsilon4 allele, but the APOE epsilon2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear.

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PubMed2004

Predicting the rate of cognitive decline in aging and early Alzheimer disease.

OBJECTIVES: To determine prognostic factors affecting the course of Alzheimer disease (AD) and to determine the role of region-specific brain volumes as predictors of cognitive decline. METHODS: Longitudinal data from 166 normal elderly individuals and 59 early AD patients were analyzed. Brain volumes were extracted from MRI scans using semiautomated recursive segmentation methods. Prognostic factors were considered significant if they had a significant effect on the rate of cognitive decline. RESULTS: In multivariate analysis, higher Clinical Dementia Rating Scale (CDR) score at entry was a significant prognostic factor for an increased rate of cognitive decline. Significant prognostic factors within the baseline CDR = 0 group were base rate of progression and percent total high signal intensity (HSI), percent ventricular, and percent CSF volumes. Base rate of progression, family history, and percent ventricular volume were significant prognostic factors within the CDR = 0.5 group and APOE had a marginally significant effect on the rate of cognitive decline in the CDR = 1 group. CONCLUSIONS: Percent total HSI, ventricular, and total CSF volume measures can independently predict the rate of cognitive decline and improve the predictive power of statistical models that use only clinical data. Brain volumetric measures from MRI can be used to estimate the rate of cognitive decline even among normal elderly individuals and thus may aid in the prediction of time of onset of disease.

Age of Onset↗

PubMed1996

Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease.

OBJECTIVES: To determine the association between the epsilon2 and epsilon4 alleles of apolipoprotein E (ApoE) and independent measures of cognitive decline and non-cognitive symptomatology in late onset Alzheimer's disease. METHODS: The frequency of the epsilon2 and epsilon4 alleles of ApoE and their association with measures of cognitive decline and non-cognitive symptomatology were assessed in a population based case register study of 164 patients with late onset Alzheimer's disease from the east Lambeth and south Southwark districts of south London. RESULTS: Analysis of a wide range of non-cognitive symptoms against ApoE epsilon4 genotype showed no significant association but a positive relation was found between ApoE epsilon2 genotype and depressive symptomatology (P = 0.004). No relation was found between measurements of cognitive decline and the presence of the ApoE epsilon4 allele. A trend for decreasing age at onset of 3 to 4 years in carriers of the ApoE epsilon4 allele was found, confirming earlier studies. CONCLUSION: Presence of the epsilon4 allele of ApoE is associated with an earlier age at onset but does not seem to be related to either a more severe psychopathology or a more rapid progression of the illness. The epsilon2 allele of ApoE is associated with depressive symptomatology in late onset Alzheimer's disease.

Age of Onset↗