The effect of age of onset of PD on risk of dementia.

BACKGROUND: Dementia occurs in the majority of patients with Parkinson's disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. METHODS: Two community-based studies of PD in New York (n=281) and Rogaland county, Norway (n=227) and two population-based groups of healthy elderly from New York (n=180) and Odense, Denmark (n=2414) were followed prospectively for 3-4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. FINDINGS: In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. INTERPRETATION: This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD.

Effect of smoking on global cognitive function in nondemented elderly.

BACKGROUND: Contrary to early case-control studies that suggested smoking protects against Alzheimer disease (AD), recent prospective studies have shown that elderly who smoke may be at increased risk for dementia. OBJECTIVE: To examine prospectively the effect of smoking on cognition in nondemented elderly. METHOD: In a multicenter cohort, the European Community Concerted Action Epidemiology of Dementia (EURODEM), including the Odense, Personnes Agées Quid (Paquid), Rotterdam, and Medical Research Council: Ageing in Liverpool Project-Health Aspects (MRC ALPHA) Studies, 17,610 persons aged 65 and over were screened and examined for dementia. After an average 2.3 years of follow-up, 11,003 nondemented participants were retested. Excluding incident dementia cases and those without baseline information on smoking gave an analytical sample of 9,209 persons. Average yearly decline in Mini-Mental State Examination (MMSE) score was compared among groups, adjusting for age, sex, baseline MMSE, education, type of residence, and history of myocardial infarction or stroke. RESULTS: MMSE score of persons who never smoked on average declined 0.03 point/year. The adjusted decline of former smokers was 0.03 point greater and of current smokers 0.13 point greater than never smokers (p < 0.001). Higher rates of decline by smoking were found in men and women, persons with and without family history of dementia, and in three of four participating studies. Higher cigarette pack-year exposure was correlated with a significantly higher rate of decline. CONCLUSION: Smoking may accelerate cognitive decline in nondemented elderly.

Comorbid personality disorder predicts suicide after major depression: a 10-year follow-up.

OBJECTIVE: To identify psychopathological predictors for suicide in a population of major depressed Diagnostic Statistical Manual-III (DSM-III) in-patients. METHOD: A total of 210 previous participants in multicentre antidepressant drug trials, carried out in a randomized double-blind design, were followed prospectively through a maximum of 10 years. Patients with a drug or alcohol abuse were excluded. The association between suicide and the pretreatment psychopathological profile was analysed using survival statistics. RESULTS: The suicide rate for non-melancholic depressed patients was significantly higher than for melancholic depressed patients. Comorbid personality disorder was independently associated with an increased suicide rate [relative hazard 3.41(CI: 1.15-10.10)]. CONCLUSION: The study indicates that the non-melancholic aspect of depression, and especially comorbid personality disorder, is associated with an increased suicidal vulnerability.

Age-related adverse drug reactions to clomipramine.

OBJECTIVE: The aim of this study was to determine whether age itself is a significant factor in predicting adverse drug reactions in depressed inpatients treated with clomipramine. METHOD: The study involved 150 hospitalized, depressed patients treated with 150 mg clomipramine per day. Changes in orthostatic blood pressure during treatment as well as the patients' complaint about side-effects was examined with regard to age. The sample was divided into younger (<56) and older (56-70) groups. RESULTS: No significant differences between younger and older subjects were found on any of the 44 side-effects recorded. However, older depressed patients suffer from more pronounced orthostatic hypotension than younger patients. CONCLUSION: Older depressed patients who have been treated with clomipramine suffer from more severe orthostatic hypotension than younger patients. However, with the right precautions it is safe to treat older patient up to the age of 70 years with a tricyclic antidepressant.

ICD-10 criteria for depression in general practice.

BACKGROUND: The rate of recognition of depressive disorder in general practice is reported to be low. Current classification systems, i.e. ICD-10 and DSM-III-R, and DSM-IV with operational diagnostic criteria, have led to greater agreement concerning the diagnosis of depressive disorder. The aim of this study was to assess the applicability and validity of the ICD-10 criteria for depression in general practice in Denmark. METHODS: After a 1-day training course in the ICD-10 criteria for depression, ten general practitioners, during an 8-week period assessed all patients aged 18 or older for depressive symptoms in accordance with the ICD-10 criteria. RESULTS: Among a total of 3505 consultations, 116 patients (3.3%) met the criteria for a depressive episode. Of these, 80 (68.8%) accepted to be reinterviewed by a psychiatrist, who confirmed the diagnosis of depressive disorder in 57 of the 80 patients (71.3%). LIMITATIONS: The number of 'false negative' cases are unknown in the study. CONCLUSION: The ICD-10 criteria for depression seem to be appropriate and valid in general practice.

Differences in symptomatology and diagnostic profile in younger and elderly depressed inpatients.

BACKGROUND: Depression is the most prevalent psychiatric disorder in the elderly and several studies indicate that 10-15% of persons over 65 years suffer from significant depressive symptoms. Despite the high prevalence, most cases of depression in the elderly remain unrecognized and untreated, maybe because of a different pattern of symptoms across age groups. The objective of the study was to compare symptomatology and diagnostic profile between younger and elderly DSM-III and DSM-III-R major depressed inpatients and to advise an appropriate depression scale for the elderly. METHODS: The study covers 461 depressed inpatients evaluated with the Hamilton Depression Scale and the Newcastle 1965 Scale. To find differences between younger and elderly patients, the symptomatology was analyzed stepwise by principal component analyses, latent structure analyses and single item analyses. RESULTS: No clinically significant differences in symptomatology between younger and elderly depressed patients were found. The DSM-IV concept of Major Depression and the ICD-10 criteria for depression was not influenced by patients' age. LIMITATIONS: All patients were hospitalized and mainly endogenously depressed and generalization of the results to other populations should be made with caution. Only pretreatment data was analyzed. CONCLUSIONS: The DSM-IV concept of Major Depression and the ICD-10 criteria for depression can be used without modification for age.

Risk of dementia in Parkinson's disease: a community-based, prospective study.

OBJECTIVE: To calculate the incidence of and determine possible risk factors for dementia in PD. BACKGROUND: Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown. METHODS: A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group. RESULTS: Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score < 29 (OR, 3.3; 95% CI, 1.3 to 8.2). CONCLUSIONS: Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.

CAMCOG as a screening instrument for dementia: the Odense study. Cambridge Cognitive Examination.

OBJECTIVE: The Cambridge Cognitive Examination (CAMCOG) score is correlated with age and sociodemographic variables. The aim of the study was to determine an individualized CAMCOG cut-off score for dementia, taking such correlates into account. METHOD: From the general population 150 people aged 65-84 years were examined with CAMDEX which includes CAMCOG, and a neuropsychological test battery. Data from 130 non-demented people were entered in setwise multiple regression analyses to identify variables predicting the CAMCOG score. RESULTS: The variables age, social class, matrimonial status, general knowledge and intellectual level explained 66% of the variance of the CAMCOG scores. A cut-off defined as a difference between actual and predicted CAMCOG score < or = -4.41 resulted in a sensitivity of 88.2% and a specificity of 89.2% for very mild to moderate dementia. CONCLUSION: It is possible to determine an individualized CAMCOG cut-off score for dementia in its early stages.

[Prevalence and incidence of dementia in Denmark. The Odense study]. / Praevalens og incidens af demens i Danmark. Odense-undersøgelsen.

Prevalence and incidence of dementia were determined for 65-84 year-old persons living in the municipality of Odense and randomly drawn from the Danish Civil Registration System (DCRS). All participants were examined with CAMCOG, the cognitive section of CAMDEX (The Cambridge Examination for Mental Disorders of the Elderly) and the follow-up period was two years. Individualized CAMCOG cut-off scores were determined by multiple linear regression. Possibly demented persons were further examined with the remaining part of CAMDEX and neuropsychological tests. Alzheimer's disease (AD) was diagnosed according to the NINCDS-ADRDA criteria for probable AD, and vascular dementia (VD) and dementias of other types according to the DSM-III-R criteria for dementia. The severity of dementia was determined according to the Clinical Dementia Rating scale. Of the 5,237 persons drawn from the DCRS, 3,346 participated in the prevalence study and 2,452 in the incidence study. The prevalence was 7.1% (66.7% AD, 18.3% VD, and 15.0% dementias of other types). Ninety-six (2.8%) were diagnosed as very mildly demented. The incidence rate was 29.5 new cases per 1,000 person-years and 20.9 for AD. Inclusion of cases with very mild dementia resulted in higher prevalence and incidence rates than generally reported.

Cost function estimation: the choice of a model to apply to dementia.

Statistical analysis of cost data is often difficult because of highly skewed data resulting from a few patients who incur high costs relative to the majority of patients. When the objective is to predict the cost for an individual patient, the literature suggests that one should choose a regression model based on the quality of its predictions. In exploring the econometric issues, the objective of this study was to estimate a cost function in order to estimate the annual health care cost of dementia. Using different models, health care costs were regressed on the degree of dementia, sex, age, marital status and presence of any co-morbidity other than dementia. Models with a log-transformed dependent variable, where predicted health care costs were re-transformed to the unlogged original scale by multiplying the exponential of the expected response on the log-scale with the average of the exponentiated residuals, were part of the considered models. The root mean square error (RMSE), the mean absolute error (MAE) and the Theil U-statistic criteria were used to assess which model best predicted the health care cost. Large values on each criterion indicate that the model performs poorly. Based on these criteria, a two-part model was chosen. In this model, the probability of incurring any costs was estimated using a logistic regression, while the level of the costs was estimated in the second part of the model. The choice of model had a substantial impact on the predicted health care costs, e.g. for a mildly demented patient, the estimated annual health care costs varied from DKK 71 273 to DKK 90 940 (US$ 1 = DKK 7) depending on which model was chosen. For the two-part model, the estimated health care costs ranged from DKK 44714, for a very mildly demented patient, to DKK 197 840, for a severely demented patient.

Education and the risk for Alzheimer's disease: sex makes a difference. EURODEM pooled analyses. EURODEM Incidence Research Group.

The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (< or =7), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28,061 (27,839) person-years of follow-up. Compared with women with a high level of education, those with low and middle levels of education had 4.3 (95% confidence interval: 1.5, 11.9) and 2.6 (95% confidence interval: 1.0, 7.1) times increased risks, respectively, for Alzheimer's disease. The risk estimates for men were close to 1.0. Finding an association of education with Alzheimer's disease for women only raises the possibility that unmeasured confounding explains the previously reported increased risk for Alzheimer's disease for persons with low levels of education.

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group.

OBJECTIVE: To study the difference in risk for dementing diseases between men and women. BACKGROUND: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. METHODS: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. RESULTS: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). CONCLUSION: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.

Characteristics of elderly who develop Alzheimer's disease during the next two years-a neuropsychological study using CAMCOG. The Odense Study.

OBJECTIVE: The aim of the study was to determine which cognitive functions first deteriorate in Alzheimer's disease (AD) and to identify persons who would become demented 2 years following an initial examination. PARTICIPANTS: A total of 2452 initially non-demented persons, aged 65-84 years and randomly drawn from the population, who were examined 2 years apart. MEASURES: CAMCOG, the cognitive section of CAMDEX (The Cambridge Mental Disorders of the Elderly Examination). Fourteen composite measures were constructed of the 60 CAMCOG items. RESULTS: During the 2-year period, 102 developed AD; this group had significantly lower scores on all of the 14 composite measures at baseline examination than the subjects who remained non-demented. The incident demented were significantly older than the non-demented, had less formal schooling, were more often unskilled and had lower verbal intellectual level. Logistic regression analyses showed that especially higher age, together with reduced recent and remote memory, low category verbal fluency and attentional deficiency, characterized incident demented 2 years before the diagnosis was made. CONCLUSIONS: Cognitive changes, which develop years before the AD diagnosis, can be identified by means of CAMCOG, but this instrument does not allow identification of persons who later develop AD with sufficient precision.

The cost of dementia in Denmark: the Odense Study.

In a population-based study of dementia, the cost of care for 245 demented elderly and 490 controls matched by age and gender was estimated. Dementia of Alzheimer's type was diagnosed according to the NINCDS-ADRDA criteria, and vascular dementia and other types of dementia were diagnosed according to the DSM-IIIR criteria. Severity of dementia was determined by the Clinical Dementia Rating scale. The annual cost of medical care, domestic care, home help, nursing home and special equipment for nondemented patients was DKK 22,000 per person while the cost for very mildly, mildly, moderately and severely demented patients was DKK 49,000, DKK 93,000, DKK 138,000 and DKK 206,000, respectively. Except for very mild dementia the cost did not differ between elderly who suffer from Alzheimer's disease and those with other types of dementia. The net cost of dementia is the difference in cost between those with dementia and the matched controls and amounts on average to DKK 77,000 per person per year. However, priority setting cannot be based on the cost of dementia per se, but only on the cost of a specific dementia intervention compared to its health benefit.

Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia.

OBJECTIVE: To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma. BACKGROUND: These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled. METHODS: The authors performed a pooled analysis of four European population-based prospective studies of individuals 65 years and older, with 528 incident dementia patients and 28,768 person-years of follow-up. Patients were detected by screening the total cohort with brief cognitive tests, followed by a diagnostic assessment of those who failed the screening tests. Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (revised), and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Incident rates and relative risk (95% CI) express the association of a risk factor for dementia. RESULTS: Incident rates for dementia and AD were similar across studies. The incidence of AD increased with age. At 90 years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000 person-years. Female gender, current smoking (more strongly in men), and low levels of education (more strongly in women) increased the risk of AD significantly. A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly. CONCLUSION: Contrary to previous reports, head trauma was not a risk factor for AD, and smoking did not protect against AD. The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies. Female gender may modify the risk of AD, whether it be via biological or behavioral factors.

Incidence of very mild to severe dementia and Alzheimer's disease in Denmark: the Odense Study.

OBJECTIVE: Calculation of incidence of dementia and AD, including cases in the earliest phases of the diseases. BACKGROUND: Establishment of incidence estimates is important for the future planning of the health care system, and incidence studies can offer insights into risk factors. METHODS: A total of 5,237 persons age 65 to 84 years were randomly drawn among people living in the municipality of Odense, Denmark. Of this sample 3,086 persons were eligible for the incidence study. All participants were examined with CAMCOG, the cognitive section of The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), and the follow-up period was 2 years. Using multiple linear regression, the CAMCOG cutoff score was individualized to detect even minor cognitive decline with optimal precision. Possibly demented persons were further examined with the remaining part of the CAMDEX and neuropsychological tests. AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD, and vascular dementia and dementia of other types were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised) criteria for dementia. Finally, the severity of dementia was determined according to the Clinical Dementia Rating scale. RESULTS: The incidence rate for very mild to severe dementia was 29.5 per 1,000 person-years and 20.9 for AD, and the rates were similar for men and women. CONCLUSION: Application of an individualized cutoff for the screening instrument resulted in detection of a substantial number of cases with very mild dementia, which subsequently resulted in higher incidence rates than those reported in most other studies.

Age-associated memory impairment--pathological memory decline or normal aging?

The aim of the study was to determine whether the memory capacity of individuals with age-associated memory impairment (AAMI) over a period of approximately 3 1/2 years declines more, if at all, than the memory capacity of persons without AAMI. Four computerized and three non-computerized memory tests, a naming test, and a test of visuo-motor speed were administered twice. Two estimates of intellectual capacity were made, one at the first examination and the other 3 1/2 years later. One person in the AAMI group (n = 44) developed vascular dementia. The group of AAMI subjects did less well on two of the seven memory tests after 3 1/2 years than they did initially; the control group (n = 18) had lower scores on one memory test at follow-up than they had previously. The data suggest that the memory capacity of subjects with AAMI is not pathologically impaired. The general intellectual level significantly influences whether an individual with memory complaints will be classified AAMI or not. People with high intelligence are less likely than people with lower intellectual capacity to fulfill the AAMI criteria. This suggests that AAMI lacks in construct validity.

Are in-patient depressives more often of the melancholic subtype? Danish University Antidepressant Group.

In contrast to out-patients, hospitalized depressed patients have been reported to respond better to tricyclic antidepressants (TCAs) than to selective serotonin reuptake inhibitors (SSRIs) and moclobemide. This may be due to differences in the type of patients included in the trials. The hypothesis that hospitalized depressed patients have a different symptom profile to out-patients was tested by comparing 352 patients from three in-patient studies with 581 patients from three out-patient studies conducted in Denmark during the period 1980-1992. All patients had major depression and were evaluated using the Hamilton Depression Scale. The full version of the Newcastle Diagnostic Rating Scale (1965) was applied to 443 of the patients. In-patients were characterized by higher scores on the items 'depressed mood', 'suicidal impulses', 'work and interest (reduced)', 'retardation', 'distinct quality of depression', 'weight loss', 'feeling of guilt' and 'nihilistic delusions', and by lower scores on the items 'somatic complaints', 'hypochondriasis', 'psychological stressors' and 'anxiety'. In total, 76% of the in-patients and 40% of the out-patients had melancholic/endogenous depression. These findings may explain why TCAs are superior to SSRIs and moclobemide in hospitalized patients, since other data indicate that TCAs seem to be the most effective treatment for the melancholic/endogenous subtype.

The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline.

The dexamethasone suppression test (DST) was conducted in 95 elderly DSM-III-R depressed patients randomized for treatment with moclobemide (MOC; 400 mg daily), nortriptyline (NT; 75 mg daily), or placebo (PBO) in a 7-week double-blind multicenter study. Patients were assessed weekly using various clinical scales, including the 17-item Hamilton Depression Rating Scale. The DST was administered at baseline and at the end of treatment. At baseline, no relationship was found between DST status and the various clinical scales used. At the end of treatment, suppressors (DST-) had significantly improved clinical ratings compared to nonsuppressors (DST+), and were mostly found among those treated with NT (71%) as compared to MOC (41%) or PBO (33%) (p < .03). On the other hand, baseline DST measures influenced treatment outcome; DST+ patients had a greater number of treatment responders to NT (48%) than MOC (19%) or PBO (20%) (p < .07). For DST- patients, the situation was reversed: NT, 7%; MOC, 31%. Postdexamethasone cortisol levels were lower in MOC responders (p < .07). An interaction was found between DST and drug-specific response. The DST may be a useful adjunct for predicting and evaluating the outcome of antidepressant therapy.

Prevalence of very mild to severe dementia in Denmark.

OBJECTIVES: The prevalence of dementia has been estimated in several countries and a meta-analysis has shown moderate and severe dementia in people aged 65 years and older to be between 4% and 6%. The Odense study is aiming to estimate the prevalence and incidence of dementia and to identify risk factors. MATERIAL AND METHODS: A total of 3346 persons, equivalent to 64.5% of a random sample of 5237 persons aged 65-84 years living in the municipality of Odense, Denmark, underwent a two phase diagnostic procedure including a screening with CAMCOG, the cognitive section of The Cambridge Examination for Mental Disorders of the Elderly, seven neuropsychological tests, medical examination, and CT scan. The severity of dementia was assessed by the CDR (Clinical Dementia Rating). RESULTS: The prevalence rate was 7.1%, including the very mildly demented, defined as persons rated questionably demented according to the CDR scale. The prevalence rate of very mild dementia was 2.8%. The proportion of cases with very mild dementia decreased with increasing age while the prevalence rate increased. CONCLUSION: Inclusion of very mild cases of dementia resulted in a higher prevalence rate than generally reported, and the prevalence rate increased exponentially with age which was mainly due to Alzheimer's disease.