Normal pressure hydrocephalus (NPH), described by Hakim and Adams in 1965, is characterized by gait apraxia, urinary incontinence, and dementia. It is associated with normal cerebrospinal fluid (CSF) pressure and ventricular dilation that cannot be attributed to cerebral atrophy. Objectives: To evaluate gait characteristics in patients with idiopathic NPH and investigate the effect of the CSF tap test (CSF-TT) on gait. Methods: Twenty-five patients diagnosed with probable idiopathic NPH were submitted to the CSF-TT. The procedure aimed to achieve changes in gait parameters. Results: Fifteen gait parameters were assessed before and after the CSF-TT. Five showed a statistically significant improvement (p < 0.05): walking speed (p < 0.001), cadence (p < 0.001), step length (p < 0.001), en bloc turning (p = 0.001), and step height (p = 0.004). Conclusion: This study demonstrated that gait speed was the most responsive parameter to the CSF-TT, followed by cadence, step length, en bloc turning, and step height.

Alzheimer's disease (AD) is a neurodegenerative disorder in which there is a decline of cholinergic function. The symptomatic AD treatment involves the use of ChEIs (cholinesterase inhibitors) as rivastigimine, a dual inhibitor. The human butyrylcholinesterase (BChE) is an enzyme that has specific roles in cholinergic neurotransmission and it has been associated with AD. In the serum, BChE is found in four main molecular forms: G1 (monomer); G1-ALB (monomer linked to albumin); G2 (dimer); and G4 (tetramer). The interaction between the products of BCHE gene and CHE2 locus results in CHE2 C5+ and CHE2 C5- phenotypes. CHE2 C5+ phenotype and BChE-K are factors that influence on BChE activity. This work aimed to verify the proportions of BChE molecular forms, total and relative activity in 139 AD patients and 139 elderly controls, taking into account K variant, CHE2 locus, rivastigmine treatment and clinical dementia rating (CDR) of AD patients. Phenotypic frequencies of CHE2 C5+ and frequency of the carriers of the K allele were similar between groups. Total BChE activity in plasma was significantly lower in AD patients than in elderly controls. Furthermore, we found that reduction on plasma BChE activity is associated directly with AD progression in AD patients and that rivastigmine treatment has a stronger effect on BChE activity within the CDR2 group. The reduction in BChE activity did not occur proportionally in all molecular forms. Multiple regression analysis results confirmed that AD acts as the main factor in plasma BChE activity reduction and that severe stages are related with an even greater reduction. These findings suggest that the reduction of total plasma BChE and relative BChE molecular forms activity in AD patients is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic secondary marker for AD.

Objective: To evaluate the epidemiological profile of patients seen at a dementia outpatient clinic. Methods: A retrospective study conducted by medical record review searching data on sex, race, age, schooling level, and diagnosis of patients seen from 2008 to 2015. Results: A total of 760 patients were studied, with a predominance of female (61.3%; p<0.0001). The mean age was 71.2±14.43 years for women and 66.1±16.61 years for men. The most affected age group was 71 to 80 years, accounting for 29.4% of cases. In relation to race, 96.3% of patients were white. Dementia was diagnosed in 68.8% of patients, and Alzheimer's disease confirmed in 48.9%, vascular dementia in 11.3%, and mixed dementia in 7.8% of cases. The prevalence of dementia was 3% at 70 years and 25% at 85 years. Dementia appeared significantly earlier in males (mean age 68.5±15.63 years). As to sex distribution, it was more frequent in women (59.6%) than in men (40.4%; p<0.0001; OR=2.15). People with higher schooling level (more than 9 years) had a significantly younger age at onset of dementia as compared to those with lower schooling level (1 to 4 years; p=0.0007). Conclusion: Most patients seen in the period presented dementia, and Alzheimer was the most prevalent disease. Women were more affected, and men presented young onset of the disease. Individuals with higher schooling level were diagnosed earlier than those with lower level.

Background Idiopathic normal pressure hydrocephalus (INPH) is characterized by gait disturbance, urinary incontinence and cognitive decline. Symptoms are potentially reversible and treatment is based on cerebrospinal fluid shunting. The tap test (TT) is used to identify patients that will benefit from surgery. This procedure consists of the withdrawal of 20 to 50 mL of cerebrospinal fluid (CSF) through a lumbar puncture (LP) after which the symptoms of the triad are tested. Improvement in the quality and speed of gait are already recognized but cognitive improvement depends on several factors such as tests used, the time elapsed after LP for re-testing, and the number of punctures. Serial punctures may trigger similar conditions as external lumbar drainage (ELD) to the organism. Objective This study aimed to identify how serial punctures affect cognition to increase the sensitivity of the test and consequently the accuracy of surgical indication. Methods Sixty-one patients with INPH underwent baseline memory and executive tests repeatedly following the 2-Step Tap Test protocol (2-STT – two procedures of 30 mL lumbar CSF drainage separated by a 24-h interval). The baseline scores of INPH patients were compared with those of 55 healthy controls, and with intragroup post-puncture scores of the 2-STT. Results The group with INPH had lower performance than the control group in all cognitive tests (RAVLT, Stroop, CFT, FAR-COWA, FAB, MMSE, orientation, mental control), except for the forward digit span test (p = 0.707). After conducting LP procedures, the Stroop test (words, colors and errors), RAVLT (stage A1, A6 and B1), and CFT (immediate and delayed R) scores were equal to those of the control group (p > 0.05). The INPH group presented significant improvement after the first puncture in MMSE (p = 0.031) and in the Stroop Test (points) (p < 0.001). After the second puncture, subjects improved in orientation, MMSE, RAVLT (B1), Stroop (points, words, errors) and CFT (IR). Conclusion Progressive cognitive improvement occurred over the 2-STT and changes were more significant after the second LP in all cognitive domains except for RAVLT (A7). Encephalic alert system ‘arousal’ seems to participate in early improvements observed during 2-STT. The second LP increased the sensitivity of the drainage test to detect changes in cognitive variables, and consequently improved the quality of the method.

Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for secondary hydrolysis of the acetylcholine. K and -116A BCHE variants were associated with decrease in plasma BChE activity, and their influence has been investigated in diseases with a cholinergic deficit such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE genetic variants on enzymatic activity, all patients and controls were genotyped for K and -116A variants. We found lower plasma BChE activity in DLB patients compared to elderly controls and to AD independent of the presence of K or -116A variants. Our results suggest that the reduction of total plasma BChE activity is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic marker for differential diagnosis between AD and DLB.

The choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are fundamental to neurophysiological functions of the central cholinergic system. We confirmed and quantified the presence of extracellular ChAT protein in human plasma and also characterized ChAT and VAChT polymorphisms, protein and activity levels in plasma of Alzheimer's disease patients (AD; N = 112) and in cognitively healthy controls (EC; N = 118). We found no significant differences in plasma levels of ChAT activity and protein between AD and EC groups. Although no differences were observed in plasma ChAT activity and protein concentration among ChEI-treated and untreated AD patients, ChAT activity and protein levels variance in plasma were higher among the rivastigminetreated group (ChAT protein: p = 0.005; ChAT activity: p = 0.0002). Moreover, AD patients homozygous for SNP rs1880676 A allele exhibited higher levels of ChAT activity. Considering this is the first study to report the influence of genetic variability of ChAT locus over ChAT activity in AD patients plasma, it opens a new set of important questions on peripheral cholinergic signaling in AD.

The illustrious Colombian Professor Salomón Hakim provided the annals of neurology with one of the most brilliant and original bodies of research on record, developing the concept of normal pressure hydrocephalus, as well as proving that ventricular shunting is an effective treatment. Thus, Professor Hakim proved that some of the dementias, at that time considered senile, could be successfully treated. Here the authors present an historical review of his main contributions, which continue to influence the study of dementia to this day.

Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M).