A path analysis of patient dependence and caregiver burden in Alzheimer's disease.

BACKGROUND: The concept of dependence has been proposed as an integrative measure to assess the progression of Alzheimer's disease (AD).This study aimed to investigate the association of patient's dependence level with the caregiver burden within a general theoretical model that includes other well-established determinants. METHODS: Observational and cross-sectional multicenter study. The sample consisted of patients with AD recruited in outpatient consultation offices by a convenience sampling procedure stratified by dementia severity. Cognitive and functional status, behavioral disturbances, dependence level, medical comorbidities, and caregiver burden were assessed by using standardized instruments. A path analysis was used to test the hypothesized relationships between the caregiver burden and its determinants, including the level of dependence. RESULTS: The sample consisted of 306 patients (33.3% mild, 35.9% moderate, 30.7% severe), the mean age was 78.5 years (SD = 7.8), and 66.2% were women. The model fit was acceptable and explained 29% of the caregiver burden variance. Primary stressors were the level of dependence and the distress related to behavioral disturbances. Caregiver's age, gender, and co-residence with the patient were the contextual factors related to caregiver burden. The job status of the caregiver was a significant secondary stressor, functional disability was indirectly associated with caregiver burden via dependence, and frequency of behavioral disturbances was indirectly associated with the caregiver burden via distress. CONCLUSIONS: Dependence was, apart from behavioral disturbances, the most important primary stressor directly related to caregiver burden irrespective of the disease severity.

Practical application of brief cognitive tests.

INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

Prevalence and European comparison of dementia in a ≥75-year-old composite population in Spain.

OBJECTIVES: To estimate dementia prevalence in Spain. MATERIALS AND METHODS: Nine probabilistic and geographically defined samples participated. A screening design based on the MMSE was implemented. Positively screened individuals underwent clinical evaluation. The total number of cases in Spain was estimated. Prevalence was confronted to that of other European countries. RESULTS: Five hundred and forty-six persons aged ≥75 participated, 49 had dementia (35 with Alzheimer's disease [AD], 10 with vascular dementia [VD], 4 other; 25 first diagnosed in the study). Age- and sex-adjusted prevalence and estimated nationwide cases were 7.5% (95% CI 5.4-9.7), 5.6 (95% CI 3.7-7.5) and 1.4 (95% CI 0.5-2.3), and 290,000 (95% CI 208,000-372,000), 214,000 (95% CI 141,000-288,000) and 54,000 (95% CI 20,000-88,000) for dementia, AD and VD, respectively. CONCLUSIONS: Dementia prevalence in Spain is comparable to other European populations, while a high number of undiagnosed cases live in the community. The potential impact of Mediterranean diet, hypertension control and decreasing vascular risk factors is discussed.

Quality of life of patients with Alzheimer's disease: differential perceptions between spouse and adult child caregivers.

BACKGROUND/AIMS: Little research has been conducted into differences in the perceived quality of life of patients (QoL-p) when comparing spouse and adult child caregivers of people with Alzheimer's disease (AD). The aim of this study was to identify the differential variables in perceived QoL-p between patients and carers, distinguishing between spouse and adult child caregivers. METHOD: Cross-sectional analytic study of 251 patients and their carers (spouses: 112; adult children: 139) using the QoL-AD scale and sociodemographic and clinical data. RESULTS: The more positive perception of spouses was associated with higher educational levels of the caregiver and greater functional autonomy in the patient. The more negative perception of adult children was associated with greater caregiver burden and higher levels of depression in the patient. The perception of daughter caregivers showed the strongest association with mental health and burden. CONCLUSIONS: Spouse caregivers have a more positive perception of the patient's quality of life than adult child caregivers.

[Galanthamine versus donepezil in the treatment of Alzheimer's disease]. / Galantamina frente a donepecilo en el tratamiento de la enfermedad de Alzheimer.

AIM: To use comparative studies on the utilisation of the acetylcholinesterase inhibitors (AchE), galanthamine and donepezil, to evaluate the effectiveness and tolerance of the two drugs in the treatment of the symptoms of Alzheimer's disease (AD). DEVELOPMENT: A search was conducted on Medline for papers dealing with galanthamine and donepezil that had been published up to February 2007. Six comparative studies involving galanthamine and donepezil were found, although there are other studies that compare them together with other AchE inhibitors. CONCLUSIONS: Both drugs are moderately effective in the treatment of AD. Nevertheless, whereas in the case of donepezil there seems to be a positive relation between the maximum dosage and response, for galanthamine doses above 24 mg/day do not seem to offer any improvement. In general, treatment was well tolerated in all the studies. Maximum recommended doses (24 mg/day for galanthamine versus 10 mg/day for donepezil) were more often reached in patients treated with donepezil. The five most common side effects were, in order of frequency of presentation: nausea, agitation, vomiting, headache and fainting. In the long term, the most frequent side effects from anticholinesterases are, generally speaking, muscle cramps, tremors, nightmares, nausea, vomiting, fatigue, vertigo and loss of weight. The studies analysed show limitations in the design, duration, sample sizes and the titration schemes of the drugs.

[The feasibility of a registry of dementias: clinical features and diagnostic coverage]. / Viabilidad de un registro de demencias: características clínicas y cobertura diagnóstica.

INTRODUCTION AND AIM: Classic epidemiological studies do not allow to know the dementia patterns of derivation and diagnosis in a defined territory. This information is fundamental for the planning and distribution of the sanitary and social resources to a medium-to-long term. The results of a pilot-registry program for dementia cases based on the population surveillance principles is presented. MATERIALS AND METHODS: Consecutive and standardized registry of the incident dementia diagnoses of a memory unit during biennium 2004-2005. RESULTS: 670 new cases of dementia, of which 74% corresponded to Alzheimer's disease, were registered. The presenile dementias were 10.3% of the cases. The mean time between the beginning of the symptoms and the clinical diagnosis was of 2.4 years and the severity of the dementia was mild in 60.0%. 90.1% of the cases lived in their homes or in a relative's home. The hypertension, the diabetes mellitus and the antecedents of depressive disease were the more frequent pathological antecedents (> 20%). The diagnostic coverage based on the estimated dementia cases was 75% for the memory unit's reference territorial area. The diagnostic coverage for the health region of Girona was 38%. CONCLUSIONS: The registered data show the viability and validity of the proposed registry program for dementia cases. Nowadays the registry program is able to extend the diagnostic coverage all over the health region of Girona.

[Telemedicine and dementia: a need for the 21st century]. / Telemedicina y demencia: una necesidad para el siglo XXI.

INTRODUCTION: The ongoing process of information and communication technologies in health services implies a change in the conception, organization and management of these services. Telemedicine is a working method that allows health professionals to explore and/or treat a patient from an off-site location. In this review we provide a historical background on telemedicine, the evolution of its bibliometric impact, and its application for people with dementia. DEVELOPMENT: Telemedicine's applications have been developed in order to provide greater availability and easier access to healthcare to underserved people. The bibliometric study of telemedicine literature shows an increase in the number of bibliographic references related to telemedicine since 1995. During the last few years in Spain the research and development of telemedicine programs have increased significantly and at present there are telemedicine programs in all regions of the country. Although some of the needs of the patients with dementia may be unsuitable for communication and information technologies, their application could offer an added value to health services. This technology does not attempt to replace face-to-face medical consultations but rather to prevent some difficulties this kind of patients can present and improve their quality of life. CONCLUSIONS: Dementia could be an appropriate field in order to implement some telemedicine programs that may improve patient medical care, and reduce medical and management expenses for social and healthcare services.

[Characterisation and prevalence of the psychological and behavioural symptoms in patients with dementia]. / Caracterización y prevalencia de los síntomas psicológicos y conductuales en pacientes con demencia.

AIM: To assess the prevalence of behavioural and psychological symptoms (BPS's) in patients with dementia in Spain and their dementia-specific characteristics. PATIENTS AND METHODS: A cross-sectional and retrospective study of 1025 patients from 52 specialized dementia care units using the Neuropsychiatric Inventory (NPI). Patients with a probable diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD) were selected for BPS's characterisation. RESULTS: The global prevalence of BPS's was 66.7% (684 patients; 95% CI = 63.8-69.6%). BPS's were under-diagnosed in one third of cases. A total of 668 patients with NPI of 4 or superior and a diagnosis of AD (n = 380; 56.8%), DLB (n = 156; 23.3%) and PDD (n = 132; 19.7%) had a NPI mean of 21.1 (SD = 14.7), 25.6 (SD = 13.9) and 21.8 (SD = 14.2), respectively. Apathy, depression and anxiety were the most common BPS's. Delusions and hallucinations were significantly more prevalent in DLB. Dementia severity was correlated with the global NPI value and with all the sub-items, but anxiety and euphoria. The presence of agitation, euphoria or lability was associated with a deficient therapeutic fulfillment. CONCLUSION: A high prevalence of non-diagnosed BPS's was observed in the studied population. This has serious negative consequences for the quality of life of patients and their social environment. Therefore we propose an active search and subsequent correct treatment of BPS's in all patients with dementia.

[Clinical heterogeneity of Alzheimer's disease according to the age of onset]. / Heterogeneidad clinica de la enfermedad de Alzheimer segun la edad de inicio.

INTRODUCTION: The age of onset of Alzheimer's disease (AD) has been linked to the degree of clinical heterogeneity. Some studies have suggested that the presenile and senile forms may be different conditions. AIM: To describe the clinical and developmental characteristics of patients with AD according to the age of onset. PATIENTS AND METHODS: A clinical sample of AD patients was evaluated by means of the Cambridge Examination for Mental Disorders of the Elderly protocol together with other tests and clinical scales (Trail Making Test, Neuropsychiatric Inventory, Rapid-Disability Rating Scale-2 and Zarit Burden Interview). Patients were reassessed at 12 months. RESULTS: Of the 492 participants, 419 (85.2%) were cases of late-onset AD and 73 cases (14.8%) had early-onset AD. For this latter group, the time between onset of the first symptoms and diagnosis of the disease was higher (3.85 versus 2.5 years) and there was a higher frequency of family histories of dementia (35.6%) and personal histories of psychiatric disorders (13.7%). This group also presented better scores on the functional evaluation scales and on the neuropsychological tests, as well as more frequent and severe symptoms of depression. At 12 months no clinical differences were recorded between the two groups, except for an increase in the frequency and severity of apathy. CONCLUSIONS: From the differences found between early-onset and late-onset AD we cannot consider them to be two different conditions from the clinical and/or neuropsychological point of view.

[A proposal for a clinical registry of dementias]. / Propuesta para un registro clinico de demencias.

AIMS: We outline a proposal for the structural and functional features needed to develop a registry of dementias which can be used to collect standardised information that is both reliable and valid concerning cases of dementia in the specialised health care centres within a particular geographical area. DEVELOPMENT: Due to the shortage of information about aspects concerning the impact of dementias on the health care system (in terms of the usage of resources and patterns of detection, referral, diagnosis and treatment in usual clinical practice in primary and secondary care), a sequential implementation of the registry is proposed so that it can be adapted to each health district or region. The first step is to identify the cases and sources of information; second, a system for collecting data must be developed that allows information to be gathered in a standardised manner while at the same time making it possible to work in close collaboration with the specialists who diagnose dementia; and, third, it must be set up with the logistics and staff needed to centralise all the functions and activities of the registry. CONCLUSIONS: Epidemiological surveillance is an essential instrument for planning, managing and distributing community health resources, for following up the natural history of chronic diseases and for assessing the impact of programmes of prevention. In this respect, and from a functional point of view, the proposed registry of dementias meets all the basic requirements of epidemiological surveillance.

Pharmaceutical consumption and cost in patients with dementia: A longitudinal study by the Registry of Dementias of Girona (ReDeGi) in Catalonia (Spain).

OBJECTIVE: Drug spending increases exponentially from the age of 65-70 years, and dementia is one of the diseases significantly contributing to this increase. Our aim was to describe pharmaceutical consumption and cost in patients with dementia, using the Anatomical Therapeutic Chemical (ATC) classification system. We also assessed the evolution of costs and consumption, and the variables associated to this evolution during three years. METHODS: Three years prospective cohort study using data from the ReDeGi and the Health Region of Girona (HRG) Pharmacy Unit database from the Public Catalan Healthcare Service (PCHS). Frequency of consumption and costs of ATC categories of drugs were calculated. RESULTS: Sample of 869 patients with dementia, most of them with a diagnosis of degenerative dementia (72.6%), and in a mild stage of the disease (68.2%). Central nervous system (CNS) drugs had the highest consumption rate (97.2%), followed by metabolic system drugs (80.1%), and cardiovascular system drugs (75.4%). Total pharmaceutical cost was of 2124.8 € per patient/year (standard deviation (SD)=1018.5 €), and spending on CNS drugs was 55.5% of the total cost. After 36 months, pharmaceutical cost increased in 694.9 € (SD=1741.9), which was associated with dementia severity and institutionalization at baseline. CONCLUSIONS: Pharmaceutical consumption and costs are high in patients with dementia, and they increase with time, showing an association with baseline dementia severity and institutionalization. CNS drugs are the pharmaceuticals with highest prescription rates and associated costs.

Smoking and Parkinson's disease. An age-dependent risk effect? The EUROPARKINSON Study Group.

We studied the association between smoking and Parkinson's disease (PD) through a case-control study. Several studies have shown an inverse association between smoking and PD. This association has been interpreted as spurious by some investigators, and as real and causal by others. Several other studies did not confirm the inverse association. We included 193 prevalent cases of PD ascertained in five European prevalence surveys that followed a two-phase design of screening and clinical examination. Each case was matched by center, age (+/- 2 years), and gender to three control subjects drawn from the same populations (N = 579). Information on smoking was obtained through direct or proxy interview. Overall, there was no association between ever smoking and PD (odds ratio = 1.1; p = 0.6). Analyses stratified by age showed that ever smoking was associated with a decreased risk of PD in the younger individuals (odds ratio = 0.4; p = 0.03) and with a significant trend of increasing risk with advancing age (p = 0.003). The risk of PD in relation to smoking is strongly modified by age; smoking may be protective in the younger cases but not in the older cases. This finding may explain the conflicting results from previous studies.

Familial aggregation of Parkinson's disease: a population-based case-control study in Europe. EUROPARKINSON Study Group.

OBJECTIVE: To investigate the familial aggregation of PD in a large collaborative population-based case-control study. BACKGROUND: Most previous case-control studies of the familial aggregation of PD have been hospital- or clinic-based. METHODS: We included 219 prevalent cases ascertained in three European populations (centers), using a two-phase design consisting of screening and examination by a neurologist. Each case was matched by age, sex, and center to three controls drawn from the same populations (n = 657). Presence of PD among first-degree relatives (parents and siblings) was determined using the family history approach for 175 cases and 481 controls. RESULTS: Overall, a positive family history (at least one parent or sibling affected by PD) was reported in 10.3% of patients and 3.5% of controls (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.6 to 6.6). A similar association was observed when analyses were restricted to nondemented patients and controls (OR = 3.9; 95% CI = 1.7 to 8.7) or to newly diagnosed patients (OR = 3.3; 95% CI = 0.9 to 11.9). We found a significant trend of increasing risk with increasing number of affected relatives (p = 0.003). Analyses stratified by age showed a stronger association for younger PD patients (OR = 7.6; 95% CI = 1.5 to 38.9) than for older patients (OR = 2.5; 95% CI = 1.1 to 5.7). CONCLUSIONS: In this large sample of prevalent PD patients and population-matched controls, PD significantly aggregates in families, with the strength of the association being age-dependent. Therefore, familial factors, which can be genetic, environmental, or both, play a role in PD.

Parkinson's disease, smoking, and family history. EUROPARKINSON Study Group.

There is growing evidence that both genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). The hypothesis of an interaction between genetic and environmental risk factors has been little explored, and never using a population-based case-control study design. Our objective was to investigate the possible interaction between smoking and family history in the etiology of PD, as part of a collaborative population-based case-control study. We included 149 nondemented PD patients ascertained in three European prevalence surveys using a two-phase design. Each patient was matched by age (+/-2 years), gender, and center to three controls drawn from the same populations (n=375). Presence of PD among first-degree relatives and smoking history were assessed through an interview for 127 cases and 306 controls. In the overall sample we found suggestive evidence that family history and ever-smoking interact in determining the risk of PD (P=0.09), with individuals exposed to both risk factors having the highest risk (OR=10.0; 95% CI=2.0-49.6). Analyses were repeated after stratification into two age-groups (cutoff: 75 years). In older patients, the joint exposure to both risk factors was associated with a significant increase in the risk of PD (OR=17.6; 95% CI=1.9-160.5). Among younger subjects, the OR for joint exposure was not significant. In conclusion, our findings suggest that smoking and family history interact synergistically on a multiplicative scale in determining the risk of PD in individuals older than 75 years.

Apolipoprotein E4 allele frequency in Spanish Alzheimer and control cases.

We have found an APOE epsilon 4 allelic frequency of 0.289 (95% CI 0.195-0.383) in Spanish AD patients (n = 88; average age = 71.2 +/- 9.37) and of 0.061 (95% CI 0.023-0.099) in age-matched controls (n = 147; average age = 71.5 +/- 10.29). Remarkably no ApoE 4/4 subjects were observed in any of the age-matched control groups compared to a total of 22 AD patients with the ApoE 4/4 phenotype. The combined odds ratio for subjects with one or two epsilon 4 alleles in the present study is 6.25 (95% CI 3.13-12.60), which is one of the highest so far reported. Altogether our results suggest a trans-European difference in the ApoE epsilon 4 frequency but no differences in the strength of the association between APOE4 and AD.

The genotype 2/2 of the presenilin-1 polymorphism is decreased in Spanish early-onset Alzheimer's disease.

We have found a significantly lower frequency of the presenilin-1 (PS-1) intronic polymorphism 2/2 genotype in early-onset Alzheimer's disease (AD) patients without APOE epsilon4 alleles (2/2 = 0.054; P = 0.009) as compared to age matched non-epsilon4 controls (2/2 = 0.227). Moreover the average age of onset in AD patients with the PS-1 2/2 genotype is older than that in AD patients with a 1/2 genotype or with a 1/1 genotype. This data suggest a protective effect of the 2/2 genotype which would delay the age of onset in AD. Our results do not support an association between the 1/1 genotype and AD. However, a non-significant increase of the 1/1 genotype is found in non-epsilon4 AD patients (P = 0.20).

[Transitory ischemic accidents. A retrospective study of 150 cases of ischemic infarction in the region of the median cerebral artery (author's transl)]. / Los accidentes isquémicos transitorios. Estudio retrospectivo de 150 casos de infarto isquémico en el territorio de la arteria cerebral media.

Transitory ischemic accident is an episode that commences abruptly with subjective or objective neurological disturbances, persists for a brief time, and returns to normal within 24 hours of onset with complete recuperation of neurological function. Using this as a basic definition, the authors specify the characteristic symptoms of different types of transitory ischemic accident and review in retrospect 150 cases of ischemic infarction in the region of the median cerebral artery. Thirty-eight percent of the patients suffered transitory ischemic accidents prior to stroke. The symptoms included the following, in order of frequency: motor nerve disorder, sensory nerve disorders, speech disturbances, and visual defects. Most of these patients presented a definite stroke within less than one month's time following the last transitory ischemic accident. The similarity of the symptoms in both conditions was noticeable. The authors study the angiographic images, the pharmacologic and toxic previous histories, and other associated diseases in each patient. They point out, lastly, that transitory ischemic accident should be considered the first manifestation of a cerebrovascular disease and not just as an isolate, reversible episode of little importance.

[Cysticercosis and angiomatosis. Clinicopathological study of one case (author's transl)]. / Cisticercosis y angiomatosis. Estudio clinicopatológico de un caso.

This is a discussion of the clinical condition of a 49-year-old patient who had been presenting intermittent episodes of intracranial hypertension since the age of 9, at which time she suddenly began a serious psychic deterioration which impaired her normal intellectual development. A new episode of intracranial hypertension led to the emergency admittance to the medical center, and was the cause of death. The cerebral post mortem study showed a large ventricular dilatation and the existence of a translucent cysticercus of a lobular shape which was adhered by a fine filament ot the internal wall of the right ventricle, very near to Monro's foramen; the possibility, therefore, was attributed to it of having had the effect of a valve mechanism which might have been causing the crises and the intracranial hypertension. At the same time, it was also observed that there existed an angiomatosis at the level of the temporal lobe, which does not seem to be related to the process, especially because of its small area and the integrity of the blood vessels.

[Medical treatment of Alzheimer's disease]. / Tratamiento médico de la enfermedad de Alzheimer.

OBJECTIVE: To review the drugs commercially available at present and in the near future in relation to the evolution of Alzheimer disease, bearing in mind the possible psychiatric disorders which may be associated with the disease. DEVELOPMENT: The therapeutic approach is planned according to the different phases of the disease. In the preclinical phase, anti-inflammatory drugs and estrogens in post-menopausal women have been effective. In the initial phase current recognition therapy is directed basically towards correcting the break-down of acetylcholine (tacrine, donepezil, SB202026, SDZ ENA 713). For depressive symptoms serotonin levels are corrected using selective inhibitors of serotonin uptake. CONCLUSIONS: Drug treatment should be considered with the association of drugs which activate the malfunctioning circuits and/or pathways. It would also be useful to design clinical studies using pharmacological combinations of cholinergic agonists, estrogens, anti-inflammatory drugs, seligiline and/or new anti-cholinesterase drugs amongst others.

[Dementia registry: current status in Catalonia]. / Registros de demencias: situación actual en Cataluña.

OBJECTIVE: This article describes the theoretical basis on which to begin and develop a record of dementias, emphasizing particularly the records of dementias of the programme Vida als Anys in Cataluña. Records of dementias give information regarding the number of cases of dementia and also for planning use of resources as required by the population. DEVELOPMENT: A record of dementias obtains, stores, keeps up to date and re-uses information about cases of dementia in a consistent manner. There are two types of records, that dealing with the population and that of the hospital. Records of the population include information from epidemiological studies, both descriptive and analytical, and also data on public health. The hospital records follow and study the natural history of dementias from an aetiological point of view but do not use a population for reference. In Cataluña records of dementias have been done for the populations of Girona, Tarragona and Barcelona and the hospitals of Barcelona, Girona, Lleida, Martorell, Reus, Santa Coloma de Gramanet and Terrassa, as part of the programme Vida al Anys. CONCLUSIONS: In order to make satisfactory plans for care in dementia, it is necessary to create databases which are as unified and as exhaustive as possible. Unified records of dementia help understanding of the course and risk factors of the condition.