Per Kragh-Sørensen

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.

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

BackgroundDementia 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.MethodsTwo 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.FindingsIn 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.InterpretationThis study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD.

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 Alzheimers disease.

Depression and the Risk of Alzheimer Disease

Background: Several epidemiologic studies have examined depression as a risk factor for Alzheimer disease with conflicting results. Most studies relied on self-reported depression, but the agreement between self-reported depression and clinical diagnosis has been reported to be weak, thereby diluting the association. Methods: A population-based cohort in Odense, Denmark, of 3346 persons age 65–84 years was examined at baseline (1992–1994) and after 2 years (1994–1996) and 5 years (1997–1999). History of depression was collected at baseline as self-report. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Persons with a history of depression had an increased risk of Alzheimer disease both at baseline (OR = 1.7; CI = 1.0–2.7) and at follow up (at 2 years, 1.9 [1.0–3.3] and at 5 years, 1.6 [0.9–2.7]). Conclusions: Depression was associated with an increased risk of Alzheimer disease. The odds ratios were lower than generally reported from follow-up studies and are similar to cross-sectional studies.

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.

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.

Moclobemide and nortriptyline in elderly depressed patients. A randomized, multicentre trial against placebo

Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either moclobemide or placebo.

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

The aim of the study was to determine which cognitive functions first deteriorate in Alzheimers disease (AD) and to identify persons who would become demented 2 years following an initial examination.

Citalopram, a selective serotonin reuptake inhibitor: Clinical antidepressive and long-term effect — a phase II study

In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three nonendogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remaining 19 patients completed a 4–6 week treatment schedule. Of 16 endogenously depressed patients 11 responded, one was a partial responder and four did not respond. Of three patients with non-endogenous depressions, two responded and one did not respond.No correlation between plasma citalopram concentration and therapeutic outcome was found.Fourteen patients were given maintenance treatment for 8–113 weeks. One patient developed depression when the dose was reduced from 60 to 40 mg and one patient became manic. After discontinuation of treatment seven patients had a depressive relapse and six of these who again were treated with citalopram responded completely.Side effect rating scores of symptoms usually associated with depression or treatment with tricyclic antidepressants declined during treatment. Three patients complained of increased need of sleep for a period after several weeks of treatment. Apart from an unspecific, transient rise in liver enzymes in two patients, detailed biochemical laboratory tests were all normal. There were no effects on blood pressure, pulse rate, orthostatic reaction, or electrocardiogram. One patient took an overdose of citalopram resulting in plasma levels about six times higher than the average therapeutic level, but there were no signs of severe toxicity. In particular no change in consciousness, electrocardiogram or blood pressure occurred.Pharmacokinetic variables such as dose schedule, steady state kinetics, and metabolism are discussed.

The accuracy of early diagnosis and predictors of death in Alzheimer's disease and vascular dementia―a follow-up study

A total of 87 patients with mild or moderate degree of dementia of the Alzheimer type (AD) or vascular dementia (VD) was identified (DSM‐III criteria), and their cognitive capacity was evaluated by means of rating scales and psychometric tests. Three years later 30 patients (34%) were dead. Significantly more VD than AD patients died. Eight of the survivors declined to participate in a follow‐up study, and 1 patient was excluded by mistake. Of the survivors, 17 had indisputably suffered cognitive decline during the follow‐up period (4 VD and 13 AD, 35%). In the case of 11 patients (2 VD and 9 AD) cognitive decline remained doubtful, and 20 patients (9 VD and 11 AD, 42%) underwent no intellectual deterioration during the follow‐up period. The results underline the problems of early diagnosis of dementia according to DSM‐III criteria. For both sexes a high ischemia score and a low body mass index predicted death. A low score on a verbal fluency test predicted death for men but not for women, and a high difference between systolic and diastolic blood pressure increased the risk of death for men but not for women.