C. Jonker

Serum inflammatory proteins and cognitive decline in older persons.

Objective: To assess whether serum levels of the inflammatory proteins α1-antichymotrypsin (ACT), C-reactive protein (CRP), interleukin-6 (IL-6), and albumin are associated with cognitive decline in older persons. Methods: The study sample consisted of 1,284 participants in the Longitudinal Aging Study Amsterdam, aged 62 to 85 years. Cognition was assessed on general cognition (Mini-Mental State Examination [MMSE]), memory (Auditory Verbal Learning Test), fluid intelligence (Raven’s Colored Progressive Matrices), and information-processing speed (Coding Task) at baseline and at 3-year follow-up. Results: The highest tertile of ACT was associated with an increased risk of decline on the MMSE (age-, sex-, education-adjusted odds ratio [OR] 1.60; 95% CI: 1.05 to 2.43) but not on any other cognitive test score. CRP, IL-6, and albumin were not associated with cognitive decline on any cognitive test in our study. Conclusions: This population-based study showed that the serum inflammatory protein α1-antichymotrypsin is associated with cognitive decline in older persons, whereas C-reactive protein, interleukin-6, and albumin are not.

Memory Complaints and Memory Impairment in Older Individuals

OBJECTIVE: To examine whether subjective memory complaints, measured with a series of four questions, are associated with performance on cognitive tests.

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

Objective: To investigate to what extent subjective memory complaints and APOE-ε4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. Methods: We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, ≥27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task–15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. Results: Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-ε4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-ε4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-ε4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. Conclusions: Both memory complaints and APOE-ε4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-ε4 allele because they have an additional risk.

APOE-ε4 is associated with memory decline in cognitively impaired elderly

Objective: To investigate whether the association between APOE-ε4 and memory decline is modified by baseline cognition and age in a population-based elderly sample. Methods: The study sample consisted of 1,243 subjects, 62 to 85 years old, with a Mini-Mental State Examination (MMSE) score between 21 and 30 and known APOE phenotypes. Memory performance was measured with an abbreviated Auditory Verbal Learning Test (AVLT) at baseline and repeated after 3 years (n = 854). Memory decline was defined as a decrease of at least 1 SD from the mean change score on immediate recall (IR), delayed recall (DR), and retention, based on the AVLT. Results: Multivariate logistic regression analyses showed that APOE-ε4 is associated with memory decline in cognitively impaired subjects (MMSE score, 21 to 26) (OR for decline on IR adjusted for age, sex, education, and baseline recall score, 3.8; 95% CI, 1.4 to 10.0; adjusted OR for decline on DR, 2.9; 95% CI, 1.2 to 7.0; adjusted OR for decline on retention, 3.3; 95% CI, 1.1 to 10.1), but not in cognitively normal subjects (MMSE score, 27 to 30) (adjusted OR for decline on IR, 1.1; 95% CI, 0.6 to 2.0; adjusted OR for decline on DR, 1.0; 95% CI, 0.6 to 1.8; adjusted OR for decline on retention, 1.5; 95% CI, 0.7 to 3.0). In particular, cognitively impaired ε4 carriers older than 75 years were at high risk of memory decline (adjusted OR for decline on IR, 4.5; 95% CI, 1.4 to 13.8; adjusted OR for decline on DR, 3.6; 95% CI, 1.2 to 10.8; adjusted OR for decline on retention, 6.6; 95% CI, 1.5 to 29.7). Conclusions: APOE-ε4 was associated with memory decline in subjects with cognitive impairment, but not in normally functioning subjects. Contrary to AD studies, our study suggests that the risk of APOE-ε4 on memory decline does not decrease at higher ages.

Visual evoked potentials (VEPs) in senile dementia (Alzheimer type) and in non-organic behavioural disorders in the elderly; Comparison with EEG parameters

Forty-two patients with senile dementia of the Alzheimer type were compared with normal subjects (51) and with elderly patients with nonorganic psychiatric disorders (40). All were examined by EEG (routine visual inspection and power spectrum density analysis) and VEP (pattern reversal) testing. In dementia the late components (N130, P165, N220) of the VEP are delayed, but the EEG was abnormal more often than the VEP.

Stroke and apolipoprotein E (4 are independent risk factors for cognitive decline: a population-based study.

Background and Purpose Stroke and apolipoprotein E &egr;4 (ApoE &egr;4) are individually important risk factors for cognitive decline, including Alzheimer disease. It has been suggested that ApoE &egr;4 multiplies the risk for cognitive decline following stroke. In a population-based sample, using well-defined sensitive cognitive measures, this study investigates whether cognitive decline following stroke is worse for patients who carry the ApoE &egr;4 allele. Methods Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The sample consisted of 1224 subjects, aged 62 to 85 years, who participated in the 3-year follow-up examination and for whom ApoE and stroke data were complete. We assessed cognitive decline using the Mini-Mental State Examination, the Auditory Verbal Learning Test (memory: immediate and delayed recall), and the Coding Task (information processing speed). The effects of stroke and ApoE &egr;4 on cognitive decline were evaluated with ANOVA and multiple logistic regression analysis, adjusted for age, sex, education, and baseline cognition. Results A synergistic effect modification for stroke and ApoE &egr;4 on cognitive decline was not observed. Unexpectedly, instead, stroke patients carrying the &egr;4 allele demonstrated a nonsignificantly lowered risk for Mini-Mental State Examination decline (OR=0.3; 95% CI 0.1 to 1.1). ApoE &egr;4 was associated with declines in information processing speed (OR=1.5; 95% CI 1.1 to 2.1) and small declines for immediate and delayed recall. Conclusions Stroke and ApoE &egr;4 may impair cognition through distinct nonsynergistic mechanisms. The slowing of information processing speed for ApoE &egr;4 carriers was more evident than impairment in memory.

Symptoms of Anxiety and Depression in the Course of Cognitive Decline

Background/Aims: Anxiety and depression are common inpatients with cognitive decline and Alzheimer’s disease (AD), and recognition and treatment of these symptoms can improve their quality of life. The present study investigates anxiety and depression in different phases of cognitive decline. Methods: The sample consisted of five groups of elderly people in different phases of cognitive decline; four from a community-based sample (Longitudinal Aging Study Amsterdam), and one group of elderly people diagnosed with AD. ANOVAs were performed to investigate group differences in the severity and prevalence of anxiety and depression, and comorbid anxiety and depressive symptoms. Results: The prevalence rates of anxiety, comorbid anxiety and depressive symptoms and depressive symptoms follow a pattern of an increasing prevalence as cognitive performance declines and a decrease in the prevalence when cognitive functioning is severely impaired. AD patients report fewest anxiety symptoms. Conclusion: We found that the prevalence of anxiety symptoms, depressive symptoms and comorbid anxiety and depressive symptoms seems to increase in the early phase of cognitive decline, and decreases as cognitive functioning further declines. Elderly diagnosed with AD report less anxiety as expected, probably due to lack of insight caused by AD.

Early detection of Alzheimer's disease using the Cambridge Cognitive Examination (CAMCOG).

BACKGROUNDnDementia screening instruments, such as the Cambridge Cognitive Examination (CAMCOG), measure a variety of cognitive functions. However, memory impairment generally is the first sign of Alzheimers disease (AD). It seems logical, therefore, to use only memory-related items for the early detection of AD. We divided the CAMCOG into a memory section and a non-memory section, and tested the hypothesis that the memory section predicts AD better than the non-memory section. We also provide normative data for both sections.nnnMETHODSnNormal subjects (N = 169) and patients with incident AD (i.e. satisfying AD criteria between 1 and 3 years from baseline: N = 25) were participants in the Amsterdam Study of the Elderly (AMSTEL), a population-based longitudinal study on cognitive decline and dementia. Patients with prevalent AD (i.e. satisfying AD criteria at baseline: N = 155) were either recruited in a memory clinic or came from AMSTEL. Normal subjects were cognitively intact at baseline and remained so for at least 3 years. The CAMCOG was administered to all subjects. AD was diagnosed by DSM-III-R criteria.nnnRESULTSnLogistic regression analysis showed that the memory section was related to prevalent AD, whereas in multivariate analysis the non-memory section was not (after correction for the memory score and demographic characteristics). A similar analysis showed that the memory section predicted incident AD, as did a higher score on the non-memory section. The MMSE did not predict incident AD better than age alone.nnnCONCLUSIONnFor the early detection of AD it is best to use the memory and non-memory sections separately instead of the total CAMCOG score.

Increased risk of mortality in Alzheimer's disease patients with higher education? A replication study

The objective of this study was to replicate findings from an earlier study by Stern et al. of an increased risk of mortality in Alzheimers disease (AD) patients with higher levels of education and to compare this risk with the risk of death in the elderly population. As part of a community-based follow-up study on dementia (Amsterdam Study of the Elderly[AMSTEL]) a cohort of 4,051 noninstitutionalized elderly age 65 to 84 years stratified in four 5-year strata of equal size was screened for dementia using the MMSE (Mini-Mental State Examination). Those suspected of dementia received diagnostic evaluation using the CAMDEX (Cambridge examination for mental disorders in the elderly). Clinical diagnoses of probable AD were made according to NINCDS-ADRDA criteria. Thirty-six prevalent patients were diagnosed as having AD. The suspected subcohort was followed up yearly over a period of 4 years. During the three yearly follow-ups, 30 incident patients received a diagnosis as well. After 6 years mortality data were obtained from municipality records. Cox proportional hazards models adjusted for age and sex were used to estimate the relative risk of death associated with the level of education. Relative risk of death decreased (although not statistically significant) in AD patients as level of education increased (RR= 0.86; 95% CI, 0.63 to 1.19). In the full baseline sample, relative risk of death decreased as level of education increased (RR = 0.86; 95% CI, 0.89 to 0.97). In this study we could not replicate the findings of Stern et al. of an increased risk of death in more highly educated AD patients. Several major differences between the two studies, among which difference in populations used is considered to be most important, are discussed that might explain the conflicting results. We conclude that higher education is not associated with increased risk of mortality in AD patients.

Late-life depressive disorder in the community, early onset and the decrease of vulnerability with increasing age

This study examined reports of a history of psychiatric illness related to age and depression in 4051 community residents aged 65-84. Depression was twice as common among subjects with a history of psychiatric illness before age 65. 78% of depressed subjects reported no history. The rate of reported history was inversely proportionate to the subjects actual age. This did not appear to be due to recollection bias but it did match the proportions previously reported to result from excess mortality of individuals with a psychiatric history. A psychiatric history may be an important risk factor for late-life depression but in the aging process after age 65 it may become increasingly uncommon.