Cognitive decline in amyotrophic lateral sclerosis: Neuropathological substrate and genetic determinants.

Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer's disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups.

[Acceptability and compliance with the use of hip protectors in elderly patients with dementia admitted to a psychogeriatric unit]. / Aceptabilidad y cumplimiento en el uso de los protectores de cadera en ancianos con demencia ingresados en una unidad de psicogeriatría.

OBJECTIVE: To detect the percentage of patients with dementia admitted to a psychogeriatric department, who have a high risk of falls, and to evaluate acceptance and compliance with hip protectors during their stay in hospital and 2 weeks and 3 months after discharge. MATERIAL AND METHODS: We performed a hospital-based prospective cohort study. Risk of falling was evaluated on the basis of immediate bipedal standing instability or abnormal semi-tandem posture, a get-up-and-go test time of more than 20 seconds, or clinical judgement. Compliance during hospital stay was evaluated through nursing records and compliance outside hospital by telephone interviews at 15 days and 3 months after discharge. RESULTS: A total of 115 patients consecutively admitted to the psychogeriatric department of the Santa Creu Hospital in Vic were assessed. Sixty patients (52.2%) were excluded from the study, the main reason being dependence on another person for walking. Of the 55 patients included, 44 (80.0%) had a high risk of falls and were candidates for hip protectors. In-hospital compliance was 80.5% (95% CI: 65.1-91.2). The most common cause of non-compliance was removal of the hip protector by the patient. Compliance after discharge was 64.5% (95% CI: 45.4-80.8) at 2 weeks and 57.1% (95% CI: 28.9-82.4) at 3 months. CONCLUSIONS: A high risk of falling was found in a large percentage of patients with dementia who were not dependent on others for walking. Compliance was not a problem in the use of hip protectors in a high-risk population in the hospital-admission setting but was weaker in the community setting.

[Idiopathic normal pressure hydrocephalus: High incidence in people over 80 years of age]. / Hidrocefalia normotensiva idiopática: alta incidencia en mayores de 80 años.

INTRODUCTION: Idiopathic normal pressure hydrocephalus is usually observed in adults over 60 years of age. The highest incidence of cases is between 70 and 80 years-old, and it could be under-diagnosed in over 80 year-olds. OBJECTIVE: A description is presented on the overall incidence and age group incidence, the delay in the diagnosis, and main outcomes. PATIENTS AND METHODS: A descriptive study was performed on patients with idiopathic normal pressure hydrocephalus, in the population of Osona County during the years 2010-2015. RESULTS: The annual incidence rate was 4.43 per 100,000 inhabitants. The incidence increased with age; from 8.09 per 100,000 in the 60 to 69 years age group, to 23.61 per 100,000 in the 70-79 years age group of, and to 37.02 per 100,000 in the 80-89 years age. The delay in the diagnosis was 15.01 ± 10.35 months. All the patients improved after surgery, but only 73.3% of the patients maintained the improvement after one year. CONCLUSIONS: Idiopathic normal pressure hydrocephalus is an age related disease and probably underdiagnosed in the elderly. An early diagnosis and a clinical suspicion are essential in patients over 80 years old.

Systematic Screening of Ubiquitin/p62 Aggregates in Cerebellar Cortex Expands the Neuropathological Phenotype of the C9orf72 Expansion Mutation.

The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI). Positive cases were also stained for dipeptide repeats. We identified a total of 21 donors with UPPI and in all of them the C9orf72 hexanucleotide expansion was genetically confirmed. Most donors had an FTLD or to a lesser extent ALS clinico-pathological phenotype. However, 3 cases had been previously classified as having clinically and neuropathologically Lewy body disease. Other co-existing pathologies, especially of the PART-type, were also frequently encountered. This study highlights the importance of the evaluation of ubiquitin/p62-positive cytoplasmic inclusions in all neurodegenerative diseases as a good screening method for the detection of C9orf72 expansion mutation, since this mutation is not rare and can overlap with other neurodegenerative entities.

Amyotrophic lateral sclerosis: A higher than expected incidence in people over 80 years of age.

Our objective was to determine the age-specific incidence and clinical-epidemiological characteristics of an amyotrophic lateral sclerosis (ALS) cohort of patients in Catalonia (Spain). New cases diagnosed between 1 January 2004 and 31 December 2013 were 41 (20 males and 21 females), with an annual crude incidence rate of 2.7 per 100,000 person-years (95% CI 1.90-3.59). The incidence rate increased with age reaching a peak in the age group of 70-79 years. There was a non-significant decrease in the incidence rate in the group of patients over 80 years (p-value = 0.75) at 17.99 per 100,000 person years (95% CI 7.81-28.17). The percentage of patients over 80 years of age was 29.3% and over age 85 years was 9.8%. The prevalence rate at the end of the study period was 8.38/100,000 of the total population. Mean age at symptom onset was 76.0 years. Onset of symptoms was bulbar or generalized in 36.6% of cases. In conclusion, ALS incidence in Osona is within the range of other countries across Europe. Our results suggest that the age-specific incidence rate of ALS increases with age through the oldest age groups suggesting an age-risk effect to develop the disease.

Functional decline after prolonged bed rest following acute illness in elderly patients: is trunk control test (TCT) a predictor of recovering ambulation?

Authors wanted to assess the predictive value of the trunk control test (TCT) on recovering ambulation in elderly patients who have developed walking disability. The study design was a prospective study performed in a hospital-based intermediate-care unit. Twenty-one patients (mean age 78.5+/-6.7 years) were investigated, who had developed walking disability after prolonged bed rest for an acute condition. A comprehensive geriatric assessment with functional status evaluation, based on the activities of daily living (ADL) (expressed as Barthel index=BI), and instrumental activities of daily living (IADL) (expressed as Lawton index=LI), cognitive function (Mini-Mental State Examination-Folstein=MMSE), depression (Geriatric Depression Scale=GDS) and comorbidity (Charlson comorbidity index=CCI) was performed within 72h after admission. A specialist in physical medicine and rehabilitation designed a rehabilitation program. TCT was performed in all patients before they started the program. The mean TCT score of the 21 patients was 52.7+/-22.9 (range: 0-100), while this score was 47.3+/-16.9 in the 15 patients who recovered ambulation, and 66.2+/-31.4 in the rest who did not (p=0.08). No statistically significant differences were observed either in subtotal scores of the TCT between groups. Furthermore, none of the TCT cutoff point was significantly associated with recovery. Cognitive function assessed by the MMSE was significantly better in patients who recovered, than in those who did not (23.4+/-3.9 vs. 17.8+/-5.2; p<0.02). Our conclusion is that TCT has not proved to be a predictor of recovering ambulation in elderly patients. In the present study, cognitive function was significantly associated with recovery after prolonged bed rest.