Neurological Disorders in Central Spain, Second Survey: Feasibility Pilot Observational Study.

BACKGROUND: The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. OBJECTIVE: The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant. METHODS: A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist. RESULTS: In this pilot study, 567 study participants were enrolled (196 from hospitals and 371 from primary care physician lists). Of these 567, 310 completed all study procedures (questionnaires and the neurological evaluation). The study was time-consuming for several primary care physicians. Hence, a few primary care physicians from some areas refused to participate, which led to a reconfiguration of study areas. In addition, the central biobank needed to be supplemented by the biobanks of local Spanish National Health System hospitals. CONCLUSIONS: Population-based epidemiological surveys, such as the NEDICES-2, require a pilot study to evaluate the feasibility of all aspects of a future field study (population selection, methods and instruments to be used, neurological diagnosis agreement, and data collection).

Detection of Motor Impairment in Parkinson's Disease Via Mobile Touchscreen Typing.

Mobile technology is opening a wide range of opportunities for transforming the standard of care for chronic disorders. Using smartphones as tools for longitudinally tracking symptoms could enable personalization of drug regimens and improve patient monitoring. Parkinson's disease (PD) is an ideal candidate for these tools. At present, evaluation of PD signs requires trained experts to quantify motor impairment in the clinic, limiting the frequency and quality of the information available for understanding the status and progression of the disease. Mobile technology can help clinical decision making by completing the information of motor status between hospital visits. This paper presents an algorithm to detect PD by analyzing the typing activity on smartphones independently of the content of the typed text. We propose a set of touchscreen typing features based on a covariance, skewness, and kurtosis analysis of the timing information of the data to capture PD motor signs. We tested these features, both independently and in a multivariate framework, in a population of 21 PD and 23 control subjects, achieving a sensitivity/specificity of 0.81/0.81 for the best performing feature and 0.73/0.84 for the best multivariate method. The results of the alternating finger-tapping, an established motor test, measured in our cohort are 0.75/0.78. This paper contributes to the development of a home-based, high-compliance, and high-frequency PD motor test by analysis of routine typing on touchscreens.

Amyloid pet in primary progressive aphasia: case series and systematic review of the literature.

Primary progressive aphasia (PPA) is considered a heterogeneous syndrome, with different clinical subtypes and neuropathological causes. Novel PET biomarkers may help to predict the underlying neuropathology, but many aspects remain unclear. We studied the relationship between amyloid PET and PPA variant in a clinical series of PPA patients. A systematic review of the literature was performed. Patients with PPA were assessed over a 2-year period and classified based on language testing and the International Consensus Criteria as non-fluent/agrammatic (nfvPPA), semantic (svPPA), logopenic variant (lvPPA) or as unclassifiable (ucPPA). All patients underwent a Florbetapir (18-F) PET scan and images were analysed by two nuclear medicine physicians, using a previously validated reading method. Relevant studies published between January 2004 and January 2016 were identified by searching Medline and Web of Science databases. Twenty-four PPA patients were included (13 women, mean age 68.8, SD 8.3 years; range 54-83). Overall, 13/24 were amyloid positive: 0/2 (0%) nfvPPA, 0/4 (0%) svPPA, 10/14 (71.4%) lvPPA and 3/4 (75%) ucPPA (p = 0.028). The systematic review identified seven relevant studies, six including all PPA variants and one only lvPPA. Pooling all studies together, amyloid PET positivity was 122/224 (54.5%) for PPA, 14/52 (26.9%) for nfvPPA, 6/47 (12.8%) for svPPA, 101/119 for lvPPA (84.9%) and 12/22 (54.5%) for ucPPA. Amyloid PET may help to identify the underlying neuropathology in PPA. It could be especially useful in ucPPA, because in these cases it is more difficult to predict pathology. ucPPA is frequently associated with amyloid pathology.

Prognostic Significance of Mild Cognitive Impairment Subtypes for Dementia and Mortality: Data from the NEDICES Cohort.

BACKGROUND: The predictive value of diverse subtypes of mild cognitive impairment (MCI) for dementia and death is highly variable. OBJECTIVE: To compare the predictive value of several MCI subtypes in progression to dementia and/or mortality in the NEDICES (Neurological Disorders in Central Spain) elderly cohort. METHODS: Retrospect algorithmic MCI subgroups were established in a non-dementia baseline NEDICES cohort using Spanish adaptations of the original Mini-Mental State Examination (MMSE-37) and Pfeffer's Functional Activities Questionnaire (Pfeffer-11). The presence of MCI was defined according two cognitive criteria: using two cut-offs points on the total MMSE-37 score. Five cognitive domains were used to establish the MCI subtypes. Functional capacity (Pfeffer-11) was preserved or minimally impaired in all MCI participants. The incident dementia diagnoses were established by specialists and the mortality data obtained from Spanish official registries. RESULTS: 3,411 participants without dementia were assessed in 1994-5. The baseline prevalence of MCI varied according to the MCI definition (4.3%-31.8%). The follow-up was a mean of 3.2 years (1997-8). The dementia incidence varied between 14.9 and 71.8 per 1,000/person-years. The dementia conversion rate was increased in almost all MCI subgroups (p >  0.01), and mortality rate was raised only in four MCI subtypes. The amnestic-multi-domain MCI (aMd-MCI) had the best dementia predictive accuracy (highest positive likelihood ratio and highest clinical utility when negative). CONCLUSIONS: Those with aMd-MCI were at greatest risk of progression to dementia, as in other surveys and might be explored with increased attention in MCI research and in dementia preventive trials.

Under reporting of dementia deaths on death certificates using data from a population-based study (NEDICES).

Previous studies have shown that dementia is frequently omitted as a cause of death from the death certificate in patients with long-standing dementia. However, most studies exclude those undiagnosed dementia sufferers in the population. In order to overcome this problem, it is necessary to examine all the participants or to screen the population for symptoms of dementia and confirm the diagnosis with a clinical examination (two-phase approach). We used this latter methodology to estimate the proportion of reporting of dementia on death certificates in a prospective population-based study (NEDICES), involving 4,197 elderly people. Community-dwelling subjects with and without dementia were identified and followed during a median of 12.5 years, after which the death certificates of those who deceased were examined. A total of 1,976 (47.1%) died (403 subjects with dementia). Dementia was rarely reported as the primary cause of death, even in known cases of dementia (20.8%). Indeed it was reported in only 13.3% of those with mild dementia and 24.3% of those with moderate or severe dementia; in 24.9% of those with possible or probable Alzheimer's disease; and in 11.9% of those with non-Alzheimer dementia. In a stepwise multiple logistic regression analysis with the dependent variable being presence or absence of dementia on the death certificate, the significant associated independent variables were age at death, severity of dementia, and etiology of dementia. We conclude that reporting of dementia on death certificates remains poor. This suggests a lack of awareness of the importance of dementia as a cause of death.

Hip fracture in three elderly populations of central Spain: data from the NEDICES study.

There is a paucity of data concerning the specific associations between hip fracture in the elderly and other age-related conditions, as well as its impact on long-term survival. This study was aimed to estimate the prevalence, risk factors, and outcome of self-reported hip fracture (srHF) in a cohort of Spanish elderly individuals. Neurological Disorders in Central Spain (NEDICES) is a census population-based survey of the prevalence and incidence of major age-associated conditions in three areas of central Spain. Data on health status and several chronic conditions were evaluated in the baseline questionnaire (1994-1995). Odds ratios for the association between srHF and other comorbidities and health-related variables were assessed by logistic regression. A Cox model estimated the impact of srHF on 13-year all-cause mortality. The final cohort comprised 5,278 community-living elderly subjects. A total of 166 participants (3.1%) had srHF. Prevalence was associated with higher age, female gender, degree of urbanisation of residence place, lower body mass index (BMI), higher number of chronic medications, higher Pfeffer FAQ score, being unmarried (P < 0.001 for all), and infantile living conditions (P = 0.007). Participants with srHF had a higher number of associated chronic conditions (P < 0.001). In the multivariate analysis, self-reported osteoporosis, lower BMI category, rural environment during childhood, and higher age were identified as independent risk factors for srHF. Adjusted hazard ratio for mortality in the srHF group was 1.40 (95% confidence interval 1.15-1.71; P = 0.001). srHF is a common condition among community-living elderly population in Spain, and has a significant impact upon long-term all-cause mortality.

The ability of self-rated health to predict mortality among community-dwelling elderly individuals differs according to the specific cause of death: data from the NEDICES cohort.

BACKGROUND: The biomedical and psychosocial mechanisms underlying the relationship between self-rated health (SRH) and mortality in elderly individuals remain unclear. OBJECTIVE: To assess the association between different measurements of subjective health (global, age-comparative, and time-comparative SRH) and cause-specific mortality. METHODS: Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of the prevalence and incidence of major age-associated conditions. Data on demographic and health-related variables were collected from 5,278 subjects (≥65 years) in the baseline questionnaire. Thirteen-year mortality and cause of death were obtained from the National Death Registry. Adjusted hazard ratios (aHR) for SRH and all-cause and cause-specific mortality were estimated by Cox proportional hazard models. RESULTS: At baseline, 4,958 participants (93.9%) answered the SRH questionnaire. At the end of follow-up, 2,468 (49.8%) participants had died, of whom 723 (29.2%) died from cardiovascular diseases, 609 (24.7%) from cancer, and 359 (14.5%) from respiratory diseases. Global SRH independently predicted all-cause mortality (aHR for 'poor or very poor' vs. 'very good' category: 1.39; 95% confidence interval (CI): 1.15-1.69). Analysis of cause-specific mortality revealed that global SRH was an independent predictor for death due to respiratory diseases (aHR for 'poor or very poor' vs. 'very good' category: 2.61; 95% CI: 1.55-4.39), whereas age-comparative SRH exhibited a gradient effect on the risk of death due to stroke. Time-comparative SRH provided small additional predictive value. CONCLUSIONS: The predictive ability of SRH for mortality largely differs according to the specific cause of death, with the strongest associations found for respiratory disease and stroke mortality.

Rate of cognitive decline in premotor Parkinson's disease: a prospective study (NEDICES).

Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population-based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non-PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994-95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997-98, but not at baseline). A 37-item version of the Mini-Mental State Examination (37-MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37-MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3-year follow-up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal-Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD.

Mortality from Parkinson's disease: a population-based prospective study (NEDICES).

Most studies of mortality in Parkinson's disease have been clinical studies, yielding results that are not representative of the general population. We assessed the risk of mortality from Parkinson's disease in the Neurological Disorders in Central Spain (NEDICES) study, a prospective population-based study in which Parkinson's disease patients who were not ascertained through medical practitioners were also included. The cohort consisted of 5262 elderly subjects (mean baseline age, 73.0 years), including 81 with Parkinson's disease at baseline (1994-1995). Thirteen-year mortality was assessed. Two thousand seven hundred and one of 5262 subjects (51.3%) died over a median follow-up of 12.0 years (range, 0.04-14.8 years), including 66 of 81 subjects (81.5%) with Parkinson's disease at baseline and 2635 of 5181 subjects (50.8%) without Parkinson's disease at baseline. In an unadjusted Cox model, the hazard ratio of mortality was increased in subjects with Parkinson's disease (hazard ratio, 2.29; 95% confidence interval, 1.80-2.93; P < .001) versus subjects without Parkinson's disease (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, the risk of mortality remained elevated in subjects with Parkinson's disease (hazard ratio, 1.75; 95% CI, 1.32-2.31, P < .001). In additional Cox models, Parkinson's disease patients with dementia had particularly high risks of mortality (adjusted hazard ratio, 2.62; 95% CI, 1.40-4.90; P < .001). In this prospective population-based study, Parkinson's disease was an independent predictor of mortality in the elderly. Parkinson's disease patients with dementia had particularly high risks of mortality.

Population-based case-control study of cognitive function in early Parkinson's disease (NEDICES).

BACKGROUND: Population-based assessments of cognitive function in patients with early Parkinson's disease (PD) are rare. We examined whether patients with early PD have cognitive deficits when compared with matched controls METHODS: All participants were age 65 years or older (median=76 years) and were enrolled in the Neurological Disorders in Central Spain (NEDICES) study in central Spain. We identified all participants with early PD (<5 years duration) (N=46). These were matched to 138 controls. Neuropsychological test scores were compared in PD patients vs. controls. In logistic regression models, we adjusted for the effects of confounding variables. In these models, the dependent variable was the neuropsychological test score (lowest quartile vs. all other quartiles) and the independent variable was PD vs. control. RESULTS: Sixteen of 46 patients (34.8%) with early PD were previously undiagnosed. Subjective memory complaint was present in 27 (58.7%) PD patients vs. 51 (37.0%) controls (p=0.010). In logistic regression models that adjusted for gender, education, and depressive symptoms or antidepressant use, PD patients performed less well on the 37-item version of the Mini-Mental State Examination (p=0.04), animal (p<0.001) and fruit fluency (p=0.04) as well as in a delayed free recall memory test (p=0.04) than controls. CONCLUSIONS: In this population-based sample of older patients with early PD, the rate of subjective and object cognitive impairment was appreciable. Patients with PD of less than five years duration performed relatively poorly on tests of global cognition, verbal fluency and memory. Clinicians should be vigilant to these cognitive difficulties even in the early stages of PD.

Dementia-associated mortality at thirteen years in the NEDICES Cohort Study.

To evaluate the mortality, thirteen years after the baseline wave (1994), of participants suffering dementia in the Neurological Disorders in Central Spain (NEDICES) Cohort Study, we conducted a population-based cohort study in the elderly (65 years and more) with 5,278 screened participants at baseline. Mortality has been evaluated by means of the National Death Registry of Spain at 1-5-2007, 13 years after enrolment. Cox's proportional hazards regression models were used to evaluate the hazard of death according to dementia severity and type, adjusting for potential covariates (gender, age, level of education, and co-morbidity). Survival was estimated using Kaplan-Meier method. Of the 5,278 participants screened at baseline, 306 had dementia. Mortality at 13 years was: 275 deaths (89.9%) in dementia subjects; and 2,426 (49.0%) in subjects without dementia. Mortality was higher and statistically significant in dementia subjects. The degree of dementia (DSM-III-R) correlated with the risk of mortality, from mild (HR = 2.23; CI: 1.77-2.82) to moderate (HR =3.10; CI: 2.47-3.89) and severe dementia (HR = 4.98; CI: 3.85-6.44). Survival was similar in Alzheimer's disease and vascular dementia. Factors associated with higher mortality in Cox proportional hazard models were older age, male gender, and comorbidity. Using Population Attributable risk (PAR%), dementia was related to 11.3% of all deaths. Dementia intensity increases the mortality risk at ten years in the NEDICES Study as in other cohort studies. Age, gender, and co-morbidity are associated with higher mortality in dementia patients. Almost one third of deaths in persons over 85 years-old could be attributable to dementia.

Premotor cognitive status in a cohort of incident Parkinson disease patients (NEDICES).

BACKGROUND: A variety of symptoms may precede the classical motor features of Parkinson disease (PD). However, it is not known whether cognitive dysfunction precedes the motor phase of PD. We examined whether patients with incident PD had had global cognitive function disturbances three years prior to diagnosis when compared with matched controls in a cohort of community-dwelling subjects. METHODS: All participants were age 65 years or older (median 76 years) and were enrolled in the Neurological Disorders in Central Spain (NEDICES) study in central Spain. We identified all participants with incident PD (N=23), diagnosed in the follow-up examination (1997-1998), who had performed an expanded 37-item version of the Mini-Mental State Examination (37-MMSE) at the baseline evaluation (1994-1995). These 23 were 1:4 matched to 92 controls. RESULTS: Baseline 37-MMSE scores were 27.9±4.9 (28) in PD patients and 28.7±6.5 (31) in controls (p=0.212). There were no patient-control differences in orientation, immediate recall, attention and calculation, memory recall, language, or visuospatial copying. In analyses that adjusted for several possible confounding factors, there were no case-control differences. CONCLUSIONS: In this population-based sample, patients with incident PD did not have evidence of significant global cognitive function disturbances three years prior to their diagnosis when compared with matched controls. Our data suggest that global cognitive dysfunction does not precede the diagnosis of PD.

Memory impairment in a simple recall task increases mortality at 10 years in non-demented elderly.

OBJECTIVE: To evaluate whether memory impairment detected in the three-word delayed recall task of the Mini-Mental State Examination (MMSE) increases the risk of mortality. METHODS: The NEDICES (Neurological Diseases in Central Spain) cohort study, is a population census-based study, aimed at detecting age-associated neurological diseases in people aged 65 and over, living in one rural and two urban communities in central Spain. Participants with dementia or without MMSE evaluation at baseline were excluded. Mortality was evaluated 10.67 years after enrollment. Cox's proportional hazards regression models were used to evaluate the hazard of death according to performance in the three-word delayed recall task included in the MMSE (score 0-3), adjusting for potential covariates (sex, age, level of education, and comorbidity). Survival was estimated using Kaplan-Meier method. RESULTS: The final study population comprised 3778 non-demented elderly subjects. After adjusting for confounding covariates, mortality was 52% greater in persons with the lowest memory score (0) vs. persons with the highest score (3). Hazard ratios (HR) showed a tendency to an increase in mortality from the highest to the lowest memory score, which was statistically significant for the groups with none (HR=1.52; CI=1.27-1.80) or one (HR=1.24; CI=1.04-1.48) word recall. Older age, male sex, and comorbidity were also associated with mortality, but level of education was not. CONCLUSIONS: Memory impairment in the three-word delayed free recall, a very simple task used by physicians worldwide, increases the risk of mortality at 10 years in non-demented elderly.

Risk of incident dementia in drug-untreated arterial hypertension: a population-based study.

Arterial hypertension in midlife may increase the risk of late-life dementia. Notably, there is conflicting data as to whether hypertension in the elderly (age 65 years and older) is a risk factor for dementia and Alzheimer's disease (AD). We determined whether drug-untreated hypertension was associated with a higher risk of incident dementia and AD. In a population-based study of older people in central Spain (NEDICES), non-demented participants were followed prospectively. Dementia at follow-up was diagnosed using DSM-IV criteria. Using Cox proportional hazards models, the risk of dementia was estimated in participants with drug-untreated hypertension and in participants with drug-treated hypertension versus controls. The 3,824 participants had a mean duration of follow-up of 3.2 years. Sixty-two (3.3%) of 1,870 participants without baseline hypertension developed incident dementia versus 78 (4.7%) of 1,657 with drug-treated, baseline hypertension and 19 (12.0%) with drug-untreated, baseline hypertension. In an unadjusted Cox model, risk of dementia was increased in participants with drug-untreated hypertension (relative risk [RR] =1.93, 95% confidence interval [CI]=1.15­3.23, p = 0.01) and in participants with drug-treated hypertension (RR =1.43, 95% CI= 1.02­2.0, p =0.035) versus participants without hypertension (reference group). In a fully adjusted Cox model, the risk of dementia remained increased in participants with drug-untreated hypertension (RR =2.38, 95% CI =1.32­4.29, p=0.004). Results were similar for risk of AD. Our results suggest that drug-untreated hypertension may be an independent risk factor for dementia and AD in the elderly.

Instrumental activities of daily living in the screening of dementia in population studies: a systematic review and meta-analysis.

BACKGROUND: Despite the fact that the current definitions of dementia in the DSM-IV and ICD-10 require functional deterioration for the diagnosis of dementia, it is not necessary a formal evaluation of functional capacity. OBJECTIVES: To examine the efficiency of functional assessment as a method of screening dementia in population studies. METHODS: This systematic review was based on information from MEDLINE, EMBASE, Index Médico Español (IME), and related articles. The studies included are population studies of patients over 65, in which normal and demented (established diagnosis) subjects are compared. In all of them, subjects were evaluated using the instrumental activities of daily living scale (IADL) as the method of screening for dementia. RESULTS: Two thousand three hundred and three abstracts and bibliographical references were reviewed. The authors of the selected studies were contacted and asked about other ongoing studies or indexes not included in our review in order to complete a meta-analysis. Finally, five studies were selected (n = 11.960). A meta-analysis was performed, with a statistical Q* value of 0.88 (SE 0.26). CONCLUSIONS: The functional assessment of the IADL showed an acceptable efficiency for the screening of dementia in the population studies included in this review, although few studies have verified this efficiency (sensitivity and specificity of the scales used). Further research is necessary in this field to be able to draw definitive conclusions.