Are specific symptoms of depression predictive of Alzheimer's dementia?

OBJECTIVE: To investigate whether specific symptoms of major depression are associated with later development of possible or probable Alzheimer's dementia. METHOD: The analysis is part of the Vienna Transdanube Aging Study, a prospective, community-based cohort study of all 75-year-old inhabitants of 2 Viennese districts. Current depressive symptoms were captured with a DSM-IV-TR-based questionnaire. Diagnosis of possible or probable Alzheimer's dementia was performed according to criteria by the National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The baseline sample included 437 not-demented and not previously depressed individuals. At 60-month follow-up, 65 of the remaining 296 subjects had possible or probable Alzheimer's dementia. The primary outcome measure was the probability of diagnosis of Alzheimer's dementia related to baseline depressive symptoms. Baseline data were collected between May 2000 and December 2002; 60-month follow-up data were collected between June 2005 and February 2008. RESULTS: 10.8% of those who were diagnosed with possible or probable Alzheimer's dementia at 60-month follow-up had shown loss of interest versus 2.2% in the nondemented group. The analysis showed a significant association of loss of interest only with the later occurrence of possible or probable Alzheimer's dementia (adjusted P value <.05, OR = 5.27 [95% CI, 1.62-17.2], area under the receiver operating characteristic curve = 0.541). The specificity of this symptom in predicting Alzheimer's dementia was 97.8, and the sensitivity was 10.4. CONCLUSIONS: Of 9 symptoms of depression, only loss of interest was associated with the development of Alzheimer's dementia over a period of 5 years in a sample of 75-year-old not-demented, never-depressed subjects, suggesting that depressive symptoms in the elderly are mostly symptoms of genuine depression.

The influence of depression on processing speed and executive function in nondemented subjects aged 75.

Neuropsychological deficits are commonly found to be part of depression in old age and might simultaneously represent early symptoms of dementia. We investigated the influence of depression on processing speed and executive function in subjects who did not develop dementia during the following 5 years to examine whether these neuropsychological dysfunctions are due to depression or are influenced by other causes (e.g., education, cerebral comorbidity). A total of 287 subjects aged 75 (mean: 75.76) were available for analyses. Processing speed was measured by the Trail Making Test-A, Executive Function by the Trail Making Test-B and Verbal Fluency. DSM-IV-criteria were used for diagnosing depression. Cerebral comorbidity (e.g., stroke, Parkinson's disease), sex, education, antidepressant, and/or benzodiazepine medication, and a history of depression were taken into account as covariates. Univariate analyses and multiple regression analyses were calculated. Higher education was strongly related to better performance in all three psychometric tests. Cerebral comorbidity significantly slowed TMT-A performance and reduced Verbal Fluency scores. In multiple regression analysis depression showed only a minor, slowing influence on TMT-A and TMT-B performance. Depression only had a minor influence on processing speed and executive function in this sample of nondemented subjects. By comparison, the influence of education and cerebral comorbidity was seen to be stronger.

Prospective study on association between plasma amyloid beta-42 and atherosclerotic risk factors.

An association between plasma Amyloid beta peptides (Aß) with blood lipids was reported in cross-sectional studies. The present study examined the 5-year prospective association of atherosclerotic risk factors with plasma Aß42 in 440 elderly persons without both Alzheimer's disease (AD) or mild cognitive impairment (MCI) at baseline. Persons in the highest tertile of total cholesterol (TC) or LDL-C at baseline showed low plasma Aß42 at 5 years. Regression analysis confirmed TC and LDL-C as negative predictors of Aß42 (p = 0.001). An increase over 5 years of HDL-C was a negative predictor and the presence of an APOE ε4 allele was a positive predictor for decrease of Aß42 in converters to MCI. In converters to AD, increase of both TC and of HbA1c were positive predictors of Aß42 levels at 5 years. Analysis of covariance showed a positive association between Δ-TC, Δ-LDL-C, Δ-HbA1c, and levels of Aß42 at 5 years (p = 0.006; 0.013 and 0.027 resp.) in converters to AD independently on lipid-lowering treatment. The association of vascular risk factors TC, LDL-C, and HbA1c with higher Aß42 levels might, after confirmation in other cohorts, influence the development of lifestyle interventions concerning plasma Aß42 and AD.

Plasma amyloid beta-42 independently predicts both late-onset depression and Alzheimer disease.

OBJECTIVES: Depression in the elderly might represent a prodromal phase of Alzheimer disease (AD). High levels of plasma amyloid beta-42 (Aß42) were found in prestages of AD and also in depressed patients in cross-sectional studies. This study examined the association of emerging late-onset depression (LOD) and AD with plasma Aß42 in a sample of never depressed and not demented persons at baseline. DESIGN: Prospective 5-year longitudinal study. PARTICIPANTS: A community dwelling of older adults (N = 331) from the Vienna Transdanube Aging study. MEASUREMENTS: Laboratory measurements, cognitive functioning, and depressive symptoms were assessed at baseline, 2.5, and 5 years follow-ups. RESULTS: After exclusion of converters to AD, regression analysis revealed that higher plasma Aß42 at baseline was a positive predictor for conversion to first episode of LOD. Independent of whether persons with mild cognitive impairment (MCI) at 2.5 years were included or excluded into regressions, higher plasma Aß42 at baseline was a significant predictor for the development of probable or possible AD at 5 years. Higher conversion to AD was also associated with male gender but not with either higher scores on the Geriatric Depression Scale (GDS), with stroke or cerebral infarction nor apolipoprotein E ε4 allele. No association was found for an interaction between plasma Aß42 levels and GDS. CONCLUSIONS: Higher plasma Aß42 at baseline predicted the development of first episode of LOD and conversion to probable or possible AD. Emerging depression as measured by scores on GDS at the 2.5-year follow-up, either alone or as an interaction factor with plasma Aß42, failed to predict the conversion to AD at 5 years.

Prediction of Alzheimer dementia with short neuropsychological instruments.

The aim of this study was to evaluate the neuropsychological instruments in predicting Alzheimer dementia after 5 years in the context of a longitudinal population-based cohort study. A total of 585 nondemented 75-year-old individuals completed neuropsychological examination at the baseline investigation; 479 subjects were followed after 30 months and 404 after 60 months. Cognition, depression and memory complaints were evaluated with psychometric instruments. Known risk factors for Alzheimer dementia were included in the analyses. Univariate logistic regression analyses and stepwise multiple models were calculated. A combination of reduced verbal memory, reduced visual motor speed, subjective memory complaints and the APOE epsilon4 carriage was best in predicting incident probable Alzheimer dementia (R(2) = 0.42, ROC curve = 0.91). The model achieved a positive predictive value of 23.3%, a negative predictive value of 98.7%, a sensitivity of 82.8% and a specificity of 82.4%. Alzheimer dementia can be predicted by neuropsychological instruments measuring episodic memory and motor speed. A high percentage of 98.7% subjects at age 75 years could be predicted as remaining non-demented at age 80 years. The prediction of those unlikely to develop AD would be more important in the future to spare further expensive diagnostic testing and protective therapies in individuals at low risk.

Late-onset depression in elderly subjects from the Vienna Transdanube Aging (VITA) study.

OBJECTIVES: To assess whether prevalence of depression increases with age. To determine possible risk factors of late-onset depression. METHOD: The Vienna Transdanube Aging (VITA) study is a community-based cohort study investigating every inhabitant of the area on the left shore of the river Danube, in Vienna, Austria, born between May 1925 and June 1926. It includes a thorough neurologic, psychiatric, and neuropsychological battery. Occurrence of a current depressive episode was diagnosed according to a DSM-IV-based questionnaire, the Hamilton Rating Scale for Depression, and the Short Geriatric Depression Scale. A gerontopsychiatric life events scale was used for the assessment of life events. 1505 subjects were contacted and 606 participated. At baseline, 406 nondemented and never-depressed individuals were included in the study. Follow-up after 30 months was possible in 331 of the 406 participants. Baseline data were collected from May 2000 to December 2002, and 30-month follow-up data were collected from November 2002 to September 2005. RESULTS: Of the 331 participants who were not depressed at baseline, 31.4% had developed a subsyndromal, minor, or major depressive episode at the 30-month follow-up; 14.2% were diagnosed with mild cognitive impairment at follow-up, 42.5% of whom were also diagnosed with new-onset depression. In the multiple analyses, "troubles with relatives" was a significant variable (p = .018, OR = 0.5, 95% CI = 0.28 to 0.89, R(2) = 0.16). Summative scores on the Fuld Object Memory Evaluation showed a significant influence (p = .048, OR = 0.9, 95% CI = 0.88 to 0.99, R(2) = 0.01) on the occurrence of newly onset depression. None of the other investigated possible risk factors had a significant influence on the new occurrence of depression. CONCLUSION: Prevalence of late-onset depression increases with age. Having severe troubles with relatives and pre-existing cognitive impairments may enhance the probability of developing a late-onset depression.

Benzodiazepine use in the elderly: an indicator for inappropriately treated geriatric depression?

OBJECTIVE: To measure the prevalence of benzodiazepine (BZD) use and to explore associated demographic and clinical variables of BZD use within a cohort of 75-year- old inhabitants of an urban district of Vienna. METHODS: This is a prospective, interdisciplinary cohort study on aging. Our investigation is based on the first consecutive 500 subjects that completed the study protocol. Demographic and clinical characteristics, benzodiazepine and antidepressant use were documented using a standardized questionnaire. Affective status was assessed using the Hamilton Depression Rating Scale (HAMD), the Geriatric Depression Scale (GDS), and the Spielberger State-and Trait Anxiety Inventory subscales (STAI). RESULTS: Prevalence of BZD use was 13.8%. Compared to non-users, BZD users had significantly higher mean scores at the HAMD (p = 0.001), the GDS (p = 0.026), and the Spielberger State-and Trait Anxiety Inventory subscales (p = 0.003; p = 0.001). Depression was found in 12.0% (HAMD) and 17.8% when using a self-rating instrument (GDS). Less than one-third of depressed subjects were receiving antidepressants. Statistically equal numbers were using benzodiazepines. CONCLUSIONS: Inappropriate prescription of BZD is frequent in old age, probably indicating untreated depression in many cases. The implications of maltreated geriatric depression and the risks associated with benzodiazepine use highlight the medical and socioeconomic consequences of inappropriate BZD prescription.

Risk factors for Alzheimer dementia in a community-based birth cohort at the age of 75 years.

BACKGROUND: Few prospective community-based cohort studies have so far concentrated specifically on the risk factors for Alzheimer dementia (AD) with onset after the age of 75 years. METHODS: We prospectively investigated a birth cohort of 585 nondemented inhabitants in the area on the East bank of the river Danube who were born between 1925 and 1926. They were investigated at the age of 75 years and followed up after 30 months. The follow-up was possible with 488 probands; 36 died, and 61 refused to participate. RESULTS: In multivariate analysis an elevated risk for late-onset AD could be found for (1) history of depressive episodes (OR = 2.09; 95% CI = 1.25-3.48); (2) the epsilon 4 allele of the APOE gene (OR = 1.86; 95% CI = 1.08-3.23); (3) lower serum level of folate (OR = 0.92; 95% CI = 0.87-0.98); (4) no chronic use of nonsteroidal anti-inflammatory drugs (OR = 0.40; 95% CI = 0.20-0.81), and (5) lower education (OR = 1.43; 95% CI = 1.03-2.00). CONCLUSIONS: Five risk factors for late-onset AD could be confirmed, which might be targets for preventive strategies.

Do subjective memory complaints predict senile Alzheimer dementia?

Many elderly complain about their memory and undergo dementia screening by the Mini-Mental State Examination (MMSE). While objective memory impairment always precedes Alzheimer dementia (AD) it is unclear whether subjective memory complaints are predicting AD. We tried to answer this question in a prospective cohort study. The 75-years old non-demented inhabitants of Vienna-Transdanube were investigated for conversion to AD after 30 months. The predictive value of subjective memory complaints was analysed in two groups: subjects with high MMSE-score (28-30) and subjects with low MMSE-score (23-27). Only in subjects with high MMSE univariate analyses showed an association between subjective memory complaints and incident AD. In both groups the verbal memory test was the main predictor of AD in multivariate analyses. We suggest to perform memory testing in subjects complaining about memory irrespective of their performance in a screening procedure like the MMSE.

Effects of medications on plasma amyloid beta (Abeta) 42: longitudinal data from the VITA cohort.

In the course of cognitive deterioration leading to Alzheimer's disease (AD) the increase of amyloid beta (Abeta42) in cerebrospinal fluid or plasma might be an initial event. We previously reported about the associations between concomitant medication and plasma Abeta42 levels in the non-demented population cohort of the Vienna transdanube aging study at baseline. In the present study, the longitudinal influence of insulin, gingko biloba, non-steroidal anti-inflammatory drugs (NSAIDs), oral anti-diabetics (sulfonylurea and biguanides), estrogens, fibrates, and statins on plasma Abeta42 are presented. Associated with medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42. Long-term users of gingko biloba, independent of their MTA, had significantly decreased plasma Abeta42 and the age-dependent increase of plasma Abeta42 was significantly smaller in long-term gingko biloba treated subjects. The use of fibrates also decreased plasma Abeta42 levels. In multiple testing considering interactions between medications, gender, APOE-epsilon4 presence and creatinine, insulin long-term users again showed significantly increased levels; fibrate and gingko biloba users showed a trend to rather decreased plasma Abeta42 levels compared to the non-users (p=0.05-0.08). Neither statins nor NSAIDs showed a significant effect on plasma Abeta42 in this model. Measuring the effect on cognition, no single medication studied was a significant predictor of conversion to AD or mild cognitive impairment (MCI). Whether the use of gingko biloba might prevent the conversion to MCI or AD needs to be proven in prospective, clinical trials.

Cumulative Exposure to General anesthesias and cognitive dysfunction at age 75 in the Vienna Transdanube Aging "VITA" study.

Some reports have described general anesthesias as a risk factor for dementia in the elderly. The authors investigated whether the number of general anesthesias during a lifetime was associated with cognitive functioning in the community-based age cohort of a geographical area of Vienna. Out of 606 seventy-five-year-old subjects, 43 reported not having undergone anesthesia and 113 reported five or more anesthesias. The number of general anesthesias was not associated with extensive psychometric data. Cognitive dysfunction at age 75 was significantly associated with level of education, a history of major head trauma, and having lived in a rural environment during childhood.

Clinical chemistry reference values for 75-year-old apparently healthy persons.

BACKGROUND: Clinical chemistry reference values for elderly persons are sparse and mostly intermixed with those for younger subjects. To understand the links between metabolism and aging, it is paramount to differentiate between "normal" physiological processes in apparently healthy elderly subjects and metabolic changes due to long-lasting diseases. The Vienna Transdanube Aging (VITA) study, which began in 2000 and is continuing, will allow us to do just that, because more than 600 male and female volunteers aged exactly 75 years (to exclude any influence of the "aging" factor in this cohort) are participating in this study. METHODS: Extensive clinical, neurological, biochemical, psychological, genetic, and radiological analyses, with a special emphasis on consumption of medication and abuse of drugs, were performed on each of the probands. The multitude of data and questionnaires obtained made possible an a posteriori approach to select individuals fulfilling criteria for a reference sample group of apparently healthy 75-year-old subjects for our study. Specific analytes were quantified on automated clinical analyzers, while manual methods were used for hormonal analytes. All clinical chemistry analytes were evaluated using in-depth statistical analyses with SPSS for Windows. RESULTS: In all, reference intervals for 45 analytes could be established. These include routine parameters for the assessment of organ functions, as well as hormone concentrations and hematological appraisals. Because all patients were reevaluated after exactly 30 months in the course of this study, we had the opportunity to reassess their health status at the age of 77.5 years. This was very useful for validation of the first round data set. Data of the second round evaluation corroborate the reference limits of the baseline analysis and further confirm our inclusion and exclusion criteria. CONCLUSIONS: In summary, we have established a reliable set of reference data for hormonal, hematological, and clinical chemistry analytes for elderly subjects. These values will be very useful for our future attempts to correlate disease states and aging processes with metabolic factors.

Subjective memory complaints and objective memory impairment in the Vienna-Transdanube aging community.

OBJECTIVES: To help answer the question of whether subjective memory complaints are a useful feature in classification systems addressing early stages of Alzheimer's disease. DESIGN: A cross-sectional investigation in the context of a community-based cohort study. SETTING: Vienna, Transdanube-a geographically defined, urban, working-class area. PARTICIPANTS: Three hundred two nondemented 75-year-olds were examined with regard to subjective memory complaints and objective memory performance. The patients were divided into two groups with respect to subjective memory complaints and into two groups with respect to memory performance on the Fuld Object Memory Evaluation. MEASUREMENTS: The percentage of individuals with memory complaints who also had objective memory impairment and the percentage of individuals with objective memory impairment who also complained about their memory were measured. RESULTS: One-tenth (10.6%) (95% confidence interval (CI)=7.7-14.7) of community based sample of 75-year-old subjects complained about their memory. There was no difference between complainers and noncomplainers with regard to actual memory performance. Only 6.3% (95% CI=0.16-30.2) of memory-impaired subjects complained about their proven memory impairment. CONCLUSION: About 94% (95% CI=69.8-99.8) of memory-impaired individuals do not complain about memory problems. Subjective memory complaints may not be a useful feature in current diagnostic criteria of mild cognitive impairment.