Julián Benito-León

Quality of life and its assessment in multiple sclerosis: integrating physical and psychological components of wellbeing

Health-related quality of life (HRQoL) has been more intensively studied in multiple sclerosis (MS) than in any other neurological disorder. Traditional medical models of impairment and disability are an incomplete summary of disease burden. Quality of life can be thought of as the sum of all sources of satisfaction (including anticipated sources) minus all threats (including anticipated threats). Many psychosocial factors-including coping, mood, self-efficacy, and perceived support-influence the quality of life of patients with MS more than biological variables such as weakness or extent of MRI lesions. Neuropsychiatric complications such as cognitive impairment and fatigue are also important predictors, even in those patients in the early stages of the disease. We review generic and specific HRQoL measures to help clinicians choose the most appropriate therapies. Subjective (self-report) HRQoL measures may serve to alert clinicians to areas that would otherwise be overlooked. Studies of new interventions should include an assessment of HRQoL not just impairment or disability alone.

Essential tremor: emerging views of a common disorder

Essential tremor (ET) is the most prevalent tremor disorder. ET has traditionally been viewed as a monosymptomatic disorder characterized by a kinetic arm tremor, but this definition is gradually being replaced. The clinical spectrum has come to include several motor features, including tremor and ataxia, and several non-motor features, including possible cognitive impairment and personality disturbances. Postmortem studies are revealing several different patterns of pathology. The emerging view is that ET might be a family of diseases, unified by the presence of kinetic tremor, but further characterized by etiological, clinical and pathological heterogeneity. Effective pharmacological treatments for the disorder remain limited, although new insights into disease mechanisms might result in more-effective therapies. In addition, recent investigations of environmental toxicants that might be linked to ET open the way towards primary disease prevention through a reduction in exposure to these factors.

Prevalence of essential tremor in three elderly populations of central Spain

Although essential tremor (ET) is considered the most prevalent adult movement disorder, the available information on its prevalence and distribution worldwide is not completely understood. We investigated the prevalence and distribution of ET in three elderly Spanish populations using a door‐to‐door, two‐phase approach. A brief screening instrument was administered on May 1, 1994 to subjects over 64 years old taken from the census of one urban municipality of Greater Madrid (quarter of Margaritas, Getafe), one urban district of Madrid (Lista), and one rural site (Arévalo county, Ávila) (N = 5,278). Study subjects were limited to those who screened positively (N = 472). To increase reliability, each patient was examined by 3 experienced neurologists, and was classified as having ET only when all 3 neurologists agreed (183 of 472). The present study was part of a large‐scale epidemiological survey of neurological diseases, and served as a baseline investigation in a 3‐year incidence study. Accordingly, 41 ET patients were identified when evaluating subjects who had screened positively for dementia, stroke, or parkinsonism, despite the fact that they had screened negatively for tremor; furthermore, 32 additional ET prevalent cases were detected when evaluating subjects who had screened positively for tremor in the second cross‐sectional study (May 1, 1997), although they had screened negatively for tremor in the first cross‐sectional study. We identified 256 persons (152 women, 104 men) with ET; of these, 87 patients (34.0%) reported having an affected relative. Two hundred and four (79.7%) of the subjects with ET were detected through this screening and had not been diagnosed previously. The prevalence of ET was 4.8% (95% CI = 4.2–5.4) for the total population; 4.6% (95% CI = 3.7–5.4) in men and 5.0% (95% CI = 4.2–5.8) in women. Age‐specific prevalence increased with advancing age for both men and women. Despite the variability in worldwide data, ET is a frequently encountered disorder in elderly people. Furthermore, as ET may be seen as a relatively benign condition, a large proportion of patients may never seek neurological attention.

Health-related quality of life and its relationship to cognitive and emotional functioning in multiple sclerosis patients

The existing knowledge about the health‐related quality of life (HRQoL) and its relationship to cognitive and/or emotional functioning in multiple sclerosis (MS) is scarce. We assessed differences between subgroups of MS outpatients (n = 209) on one HRQoL instrument: a version of the Functional Assessment of Multiple Sclerosis quality of life instrument; on two cognitive functioning tests: the Mini‐Mental State Examination and the clock drawing test; and on two emotional functioning tests: the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Three disease‐related characteristics were assessed: physical disability, duration of the illness, and clinical course. The results showed that each of these has an effect on at least one dimension of HRQoL and on one mental functioning test. Thus, the more severe, the more progressive, and the longer the illness duration, the lower the HRQoL. Likewise, cognitive mean scores decreased and emotional mean scores increased with greater illness severity and progressive the MS. Furthermore, we also found significant correlations between cognitive and emotional functioning tests and HRQoL dimensions. Thus, the worse cognitive functioning and the higher depressive and anxiety symptoms score the lower the HRQoL.

Prevalence of PD and other types of parkinsonism in three elderly populations of central Spain.

The prevalence of Parkinsons disease (PD) and other types of parkinsonism in three elderly populations of central Spain was investigated using a door‐to‐door, two‐phase approach. This design called for the administration of a brief questionnaire to subjects 65 years of age or older taken from the census of one urban municipality of Greater Madrid (Margaritas, Getafe), one rural site (Arévalo County, Ávila), and one urban district of Madrid (Lista) in Spain (N = 5,278). Study neurologists extensively investigated those subjects who screened positively. The diagnoses, based on specified criteria, were reviewed to increase reliability across neurologists. We found 118 subjects with parkinsonism: 81 affected by PD (68.6%), 26 drug‐induced parkinsonism (22.0%), 6 parkinsonism in dementia (5.1%), 3 vascular parkinsonism (2.5%), and 2 unspecified parkinsonism (1.7%). The prevalence was 2.2% (95% confidence interval [CI], 1.8–2.6) for all types of parkinsonism and 1.5% (95% CI, 1.2–1.8) for PD. The prevalence estimates of parkinsonism and PD increased with age, declining at 85 years and over. Age prevalence ratios were higher for men. Twenty‐three subjects (28.4%) of the subjects with PD were detected through the screening and had not been diagnosed previously. Overall prevalence estimates of PD and other types of parkinsonism in central Spain rank at levels similar to those recently reported for other European and non‐European elderly populations. Despite improvement in access to health services, an important proportion of PD patients may never seek neurological attention.

Population-based case-control study of cognitive function in essential tremor

Objectives: To determine whether patients with essential tremor (ET) have cognitive deficits when compared with controls and whether the types of cognitive deficits reported previously are also found in this large sampling of patients with ET. Methods: A total of 232 patients with ET and 696 matched controls age 65 years or older (median 75 years) living in central Spain (the Neurologic Diseases in Central Spain study) underwent a neuropsychological assessment, including tests of global cognitive performance, frontal executive function, verbal fluency, and memory. Subjects also were asked whether they had forgetfulness. Results: Fifty-six patients with ET were previously undiagnosed; only 14 (6%) were taking medication for tremor. Adjusted for age, gender, education, premorbid intelligence, medications, and depressive symptoms, cases performed less well on most neuropsychological tests and especially tests of global cognitive performance (37-item Mini-Mental State Examination = 27.0 ± 6.7 in cases vs 28.9 ± 5.9 in controls, p < 0.001) and frontal executive function (Trail Making Test number of errors = 8.7 ± 11.0 in cases vs 3.8 ± 7.6 in controls, p < 0.001). Forgetfulness was reported in 117 (50.4%) patients with ET vs 300 (43.1%) controls (p = 0.05). Conclusions: In a population-based sample of largely untreated patients with essential tremor, cases performed more poorly on formal neuropsychological testing than did their counterparts without tremor. A complaint of forgetfulness was also marginally more common in patients with essential tremor.

Incidence of Parkinson disease and parkinsonism in three elderly populations of central Spain

Background: A two-phase investigation method (screening followed by detailed examination) is the most accurate epidemiologic approach to estimate the epidemiology of Parkinson disease (PD) and secondary parkinsonism. The scarcity of statistics on the incidence of PD and other types of parkinsonism using this methodology led the authors to estimate them in three elderly populations. Methods: A Spanish elderly parkinsonism-free cohort was followed for an average of 3 years. At the end of the follow-up, the cohort survivors were contacted by way of screening and clinical examination. Results: The cohort consisted of 5,160 subjects (ages 65 to 85 and over): Eight hundred twenty-eight died before the examination, 3,685 completed the screening procedure, and 647 could not be screened because they refused (108) or were unreachable (539). Sixty-eight incident cases of parkinsonism were found: 30 PD (44.1%), 22 drug-induced parkinsonism (32.3%), 8 parkinsonism with associated features (11.7%), and 3 vascular parkinsonism (4.4%). The remaining five cases (7.3%) were classified as unspecified parkinsonism. Average annual incidence rate (per 100,000 person-years) in the population aged 65 to 85 and over years, adjusted to the standard European population, was 409.9 (95% CI 299.0 to 520.8) for parkinsonism and 186.8 (95% CI 110.4 to 263.2) for PD. Incidence rates of parkinsonism increased with advancing age. For PD, incidence rates increased with age in men but decreased beyond the age of 79 in women. Age-adjusted relative risk in men compared with women was 1.56 (95% CI 0.97 to 2.51) for parkinsonism and 2.55 (95% CI 1.21 to 5.37) for PD. Sixteen (53.3%) patients with PD were detected through the screening and had not been diagnosed previously. Conclusions: Incidence estimates of PD based on two-phase investigation methodology are higher than those based on other approaches. Men had a risk of developing PD that was twice that of women. A large proportion of PD patients may never seek neurologic attention.

Risk of incident dementia in essential tremor: A population‐based study

Essential tremor (ET) is a late‐life neurological disease. Mild cognitive deficits as well as an association with prevalent dementia have been reported in recent case–control studies. We determined whether ET was associated with an increased risk of incident dementia. In a population‐based study of older people in central Spain (NEDICES), nondemented ET cases and controls were followed prospectively. Incident dementia at follow‐up was diagnosed using DSM‐IV criteria and the risk of incident dementia was estimated in ET cases versus controls using Cox proportional hazards models. 3,891 participants had a mean duration of follow‐up of 3.2 years. Sixteen (7.8%) of 206 ET cases developed incident dementia versus 145 (3.9%) of 3,685 controls (unadjusted relative risk [RR] = 2.08, 95% CI = 1.24–3.50, P = 0.006 and adjusted RR = 1.66, 95% CI = 0.99–2.80, P = 0.054). In an adjusted model, ET cases with tremor onset after age 65 years were twice as likely to develop incident dementia than were controls (RR = 1.98, 95% CI = 1.14–3.45, P = 0.01), whereas ET cases with tremor onset < age 65 years and controls were equally to develop incident dementia (RR = 0.74, 95% CI = 0.19–3.20, P = 0.79). Although ET is often considered a benign condition, in this prospective, population‐based study, elderly‐onset ET was associated with an increased risk of incident dementia. The basis for this dementia, which is not known, requires additional study.

Incidence and subtypes of dementia in three elderly populations of central Spain.

OBJECTIVE To assess age-, gender, and subtype-specific incidence rates of dementia in three populations in central Spain using data from the Neurological Disorders in Central Spain (NEDICES), a population-based survey of elderly participants. METHODS Individuals were evaluated at baseline (1994-1995) and at follow-up (a median of 3.2 years later in 1997-1998). The evaluation included a screening questionnaire for dementia and a neurological assessment, when possible. RESULTS Of 5278 participants evaluated at baseline, there were 306 prevalent dementia cases. One hundred and sixty-one incident dementia cases were identified among 3,891 individuals assessed at follow-up. The large majority had Alzheimers disease (AD): 115 (71.4%) AD, 18 (11.2%) vascular dementia (VaD), 11 (6.8%) dementia associated with parkinsonism, 11 (6.8%) undetermined etiology, and 6 (3.7%) secondary dementia. Average annual incidence rates (per 1,000 person-years) in the population aged 65 to 90 and over years, adjusted to the standard European population, were 10.6 (95% CI, 8.9 to 12.3) for dementia, 7.4 (95% CI=6.0 to 8.8) for AD, and 1.4 (95% CI=0.6 to 2.3) for VaD. Age-specific incidence rates of dementia and AD increased exponentially with advancing age. Age, stroke and illiteracy were independent risk factors for dementia and AD. Aggregation of vascular risk factors was related to a higher risk of both VaD and AD. CONCLUSIONS In the NEDICES study, incidence of dementia increased with age beyond age 85 and AD was the most frequent type of dementia. The risk of AD and VaD increased with the number of vascular risk factors.

Elderly-onset essential tremor is associated with dementia

Objective: To determine whether essential tremor (ET) is associated with prevalent dementia. Methods: The authors identified all persons with dementia and ET in a population-based study in central Spain (the Neurological Disorders in Central Spain [NEDICES] Study). Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria. Results: Thirty-one (11.4%) of 273 ET cases had dementia vs 204 (6.0%) of 3,382 non-ET subjects (controls) (odds ratio [OR] = 2.00, 95% CI = 1.34 to 2.98, p = 0.001). In a model that adjusted for age, stroke, and educational level, OR = 1.35, 95% CI = 0.87 to 2.18, and p = 0.17. In an adjusted model, ET cases with tremor onset after age 65 were 70% more likely to be demented than were controls (OR = 1.70, 95% CI = 1.04 to 2.76, p = 0.03), whereas ET cases with tremor onset at age ≤65 and controls were equally likely to be demented (OR = 0.38, 95% CI = 0.09 to 1.73, p = 0.21). Conclusions: Older-onset essential tremor (ET) was associated with dementia. Prospective studies are required to elucidate the association between ET and dementia.