Jordi Gich

A clinical registry of dementia based on the principle of epidemiological surveillance

BackgroundTraditional epidemiological studies do not allow elucidating the reality of referral and diagnosis patterns of dementia in routine clinical practice within a defined territory. This information is useful and necessary in order to plan and allocate healthcare resources. This paper presents the results from a dementia case registry based on epidemiological surveillance fundamentals.MethodsStandardised registry of dementia diagnoses made in 2007 by specialised care centres in the Health Region of Girona (RSG) (Spain), which encompasses an area of 5,517 sq. km and a reference population of 690,207 inhabitants.Results577 cases of dementia were registered, of which 60.7% corresponded to cases of Alzheimers disease. Presenile dementia accounted for 9.3% of the cases. Mean time between the onset of symptoms and clinical diagnosis was 2.4 years and the severity of the dementia was mild in 60.7% of the cases. High blood pressure, a family history of dementia, dislipidemia, and a past history of depression were the most common conditions prior to the onset of the disease (>20%).ConclusionThe ReDeGi is a viable epidemiological surveillance device that provides information about the clinical and demographic characteristics of patients diagnosed with dementia in a defined geographical area.

Paroxysmal dystonia and pathological laughter as a first manifestation of multiple sclerosis

Paroxysmal dystonia is an uncommon but well-established feature of multiple sclerosis (MS). Attacks can occur in established MS and may even occasionally be the initial symptom of this disorder. Pathological laughter is usually seen as a pseudobulbar palsy in some diffuse neurological diseases, but cases have been described, mostly in ischaemic attacks or tumours, where it is presented as bursts of laughter of variable duration. The pathogenesis of neither of the two phenomena has been fully established but both have been reported as being positive phenomena resulting from ectopic activation with ephaptic spread. We describe the first reported case of a paroxysmal hemidystonia together with bursts of pathological laughter as the first manifestation of MS. Multiple Sclerosis 2008; 14: 262—265. http://msj.sagepub.com

A randomized, controlled, single-blind, 6-month pilot study to evaluate the efficacy of MS-Line!: a cognitive rehabilitation programme for patients with multiple sclerosis:

Background: MS-Line! was created to provide an effective treatment for cognitive impairment in multiple sclerosis (MS) patients. Objective: To assess the efficacy of MS-Line!. Methods: A randomized, controlled, single-blind, 6-month pilot study. Patients were randomly assigned to an experimental group (cognitive rehabilitation with the programme) or to a control group (no cognitive rehabilitation). Randomization was stratified by cognitive impairment level. Cognitive assessment included: selective reminding test, 10/36 spatial recall test (10/36 SPART), symbol digit modalities test, paced auditory serial addition test, word list generation (WLG), FAS test, subtests of WAIS-III, Boston naming test (BNT), and trail making test (TMT). Results: Forty-three patients (22 in the experimental group, 21 in the control group) were analyzed. Covariance analysis showed significant differences in 10/36 SPART (P=0.0002), 10/36 SPART delayed recall (P=0.0021), WLG (P=0.0123), LNS (P=0.0413), BNT (P=0.0007) and TMT-A (P=0.010) scores between groups. Conclusions: The study showed a significant improvement related to learning and visual memory, executive functions, attention and information processing speed, and naming ability in those patients who received cognitive rehabilitation. The results suggest that MS-Line! is effective in improving cognitive impairment in MS patients.

Neuroinflammation in obesity: circulating lipopolysaccharide-binding protein associates with brain structure and cognitive performance

Background/Objectives:Growing evidence implicates neuroinflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Obesity is associated with reduced white matter integrity and cognitive decline. Circulating lipopolysaccharide binding protein (LBP) concentration is known to be increased in patients with obesity. Here, we aimed to evaluate whether circulating LBP is associated longitudinally with white matter structure and cognitive performance according to obesity status.Subjects/Methods:This longitudinal study analyzed circulating LBP (ELISA), DTI-metrics (axial diffusivity (L1), fractional anisotropy (FA) and radial diffusivity (RD)) in specific regions of the white matter of 24 consecutive middle-aged obese subjects (13 women) and 20 healthy volunteers (10 women) at baseline and two years later. Digit Span Test (DST) was used as a measure of working memory/short-term verbal memory.Results:Circulating LBP concentration was associated with FA and L1 values of several white matter regions both at baseline and follow-up. The associations remained significant after controlling for age, BMI, fat mass and plasma high sensitivity C-reactive protein. Importantly, the increase in LBP over time impacted negatively on FA and L1 values and on DST performance.Conclusions:Circulating LBP associates with brain white matter integrity and working memory/short-term verbal memory in both obese and non-obese subjects.

Long-term clinical and radiological evolution in one case of Susac’s syndrome

Susac’s syndrome is a rare idiopathic microangiopathy affecting the precapillary arterioles of the brain, retina and cochlea leading to the clinical triad of encephalopathy, retinopathy and hearing loss. The objective of this study is to describe a new case of Susac’s syndrome reactivated after a 12-year period with a good response to immunosuppressive therapy. The patient was a 32-year-old woman, complaining of diplopia, right blurred vision, progressive gait disturbance, tinnitus, attention deficit, and slight memory loss. The patient was diagnosed as having Susac’s syndrome and discharged with steroid therapy. After a 12-year period of clinical stability she had a relapse. Immunosuppressive therapy resulted in significant clinical and radiological improvement. Early clinical identification of Susac’s syndrome is crucial for the initiation of immunosuppressive therapy and differential diagnosis. In our case, the combined use of corticosteroids and azathioprine was key in the relapse management.

The Gut Metagenome Changes in Parallel to Waist Circumference, Brain Iron Deposition, and Cognitive Function

Context Microbiota perturbations seem to exert modulatory effects on emotional behavior, stress-, and pain-modulation systems in adult animals; however, limited information is available in humans. Objective To study potential relationships among the gut metagenome, brain microstructure, and cognitive performance in middle-aged, apparently healthy, obese and nonobese subjects after weight changes. Design This is a longitudinal study over a 2-year period. Setting A tertiary public hospital. Patients or Other Participants Thirty-five (18 obese) apparently healthy subjects. Intervention(s) Diet counseling was provided to all subjects. Obese subjects were followed every 6 months. Main Outcome Measure(s) Brain relaxometry (using magnetic resonance R2*), cognitive performance (by means of cognitive tests), and gut microbiome composition (shotgun). Results R2* increased in both obese and nonobese subjects, independent of weight variations. Changes in waist circumference, but not in body mass index, were associated with brain iron deposition (R2*) in the striatum, amygdala, and hippocampus in parallel to visual-spatial constructional ability and circulating beta amyloid Aβ42 levels. These changes were linked to shifts in gut microbiome in which the relative abundance of bacteria belonging to Caldiserica and Thermodesulfobacteria phyla were reciprocally associated with raised R2* in different brain nuclei. Of note, the increase in bacteria belonging to Tenericutes phylum was parallel to decreased R2* gain in the striatum, serum Aβ42 levels, and spared visual-spatial constructional ability. Interestingly, metagenome functions associated with circulating and brain iron stores are involved in bacterial generation of siderophores. Conclusions Changes in the gut metagenome are associated longitudinally with cognitive function and brain iron deposition.

Psychotropic Drugs in Patients With Alzheimer's Disease: A Longitudinal Study by the Registry of Dementias of Girona (ReDeGi) in Catalonia, Spain

OBJECTIVES Psychotropic drugs are usually prescribed to deal with behavioral and psychological symptoms of dementia, especially when nonpharmacologic approaches are not available or have limited efficacy. Poor outcomes and serious adverse events of the drugs used must be addressed, and risk-benefit ratios need to be considered. The aim of this longitudinal study was to describe the evolution of dispensation of psychotropic drugs in patients with Alzheimers disease (AD) and to identify the associated demographic and clinical variables. METHODS Longitudinal study using 698 cases with AD included in the Registry of Dementias of Girona in 2007 and 2008 and followed up during 3 years. Drugs were categorized according to the Anatomical Therapeutic Chemical classification. Binary logistic regression analyses were used to detect the variables associated with the use of antipsychotics, selective serotonin reuptake inhibitors (SSRIs), anxiolytics, and hypnotics. RESULTS Of the patients, 51.2% consumed antipsychotics at least once during the three years of the study, whereas 73.3% and 58.2% consumed SSRIs and anxiolytics, respectively; 32.8% used hypnotics. Antipsychotic use was associated with a diagnosis of AD with delusions) [odds ratio (OR) = 5.7] and with increased behavior disorders (OR = 1.2). Patients with AD with depressed mood were more likely to be treated with SSRIs (OR = 3.1), while being a woman was associated with increased dispensation of anxiolytics (OR = 1.9) and SSRIs (OR = 2.2). CONCLUSIONS Consumption of psychotropic drugs by the patients with AD registered in the Registry of Dementias of Girona is very high. Despite all the described adverse effects and recommendations of caution in their use, antipsychotics still are extensively used.

Adherence to Clinical Practice Guidelines during Dementia Work-Up in a Real-World Setting: A Study from the Registry of Dementias of Girona

BACKGROUND There are several position statements and clinical practice guidelines (CPG) for diagnosing dementia. OBJECTIVE Our aims were to evaluate the adherence to CPG among specialists in the 7 memory clinics included in the Registry of Dementias of Girona (ReDeGi), and to compare the results between 2007-2011 and 2012-2015. We also determined the time and number of visits required to achieve a diagnosis, the supplementary tests ordered, and the drugs prescribed according to dementia subtypes. METHODS Medical charts of a stratified random sample of 475 ReDeGi cases were reviewed. Basic dementia work-up was evaluated using as a reference evidence-based CPG. An Index of Adherence (AI) was calculated using the following items in the medical chart: cognitive symptomatology; functional disability evaluation; physical examination; neurological examination; psychiatric examination; brief cognitive examination; activities of daily living performance examination; blood test; structural neuroimaging (CT-scan or MRI). RESULTS The mean AI to CPG among specialists was of 8.2 points, and it improved from 7.9 points in 2007-2011 to 8.5 points in 2012-2015 (Cohens d = 0.46). A lower adherence was detected in the most severe cases. A dementia diagnosis required 3.5 visits, regardless of the subtype of dementia, although milder cases required more time, more visits, and more supplementary tests than severe cases. CONCLUSION The adherence to CPG in the catchment area of the ReDeGi is high, and an epidemiological surveillance system such as the ReDeGi may help in improving it. Dementia guidelines should establish procedures adapted to clinical practice, with simplified recommendations for most severe cases.

Trends in the Prescription and Long-Term Utilization of Antidementia Drugs Among Patients with Alzheimer’s Disease in Spain: A Cohort Study Using the Registry of Dementias of Girona

BackgroundAcetylcholinesterase inhibitors (AChEIs) and the N-methyl d-aspartate-antagonist memantine are indicated for the symptomatic treatment of Alzheimer’s disease (AD).ObjectivesOur aims were to describe the baseline characteristics of patients with AD according to prescription of these treatments after the diagnostic work-up to describe long-term trends in the use of these medications and to identify baseline characteristics associated with the frequency of use of each treatment.MethodsThis was a cohort study with a sample of 2992 patients with AD recorded in the Registry of Dementias of Girona (ReDeGi) between 2007 and 2014. Consumption of AChEIs and memantine was assessed using the Pharmacy Unit database from the Public Catalan Healthcare Service. We used generalized estimating equation analyses to identify the baseline characteristics associated with the consumption of AChEIs and memantine over time.ResultsMost of the patients (70.4%; 95% confidence interval [CI] 68.7–72.0) were prescribed antidementia medication at the time of diagnosis. Of these, 75.0% (95% CI 73.1–76.8) were prescribed AChEIs, 14.7% (95% CI 13.2–16.3) were prescribed an AChEI plus memantine, and 10.3% (95% CI 9.0–11.6) were prescribed memantine. Advanced age reduced the likelihood of AChEI consumption. Mild dementia severity increased the use of AChEIs, and moderate–advanced dementia increased the likelihood of memantine consumption. After diagnosis, the likelihood of AChEI consumption decreased from the first year until the fifth, whereas the likelihood of memantine consumption, either alone or in combination with AChEIs, increased.ConclusionsAntidementia drug use in this study showed the initial use of AChEIs alone with later use of AChEIs in combination with memantine and memantine alone in older patients with severe AD. Our findings are in agreement with current clinical practice guidelines for the pharmacological treatment of AD.

A new cognitive rehabilitation programme for patients with multiple sclerosis: the ‘MS-line! Project’

Background: Cognitive rehabilitation is often delayed in multiple sclerosis (MS). Objective: To develop a free and specific cognitive rehabilitation programme for MS patients to be used from early stages that does not interfere with daily living activities. Methods: MS-line!, cognitive rehabilitation materials consisting of written, manipulative and computer-based materials with difficulty levels developed by a multidisciplinary team. Results: Mathematical, problem-solving and word-based exercises were designed. Physical materials included spatial, coordination and reasoning games. Computer-based material included logic and reasoning, working memory and processing speed games. Conclusions: Cognitive rehabilitation exercises that are specific for MS patients have been successfully developed.