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Importance: We previously reported that children with the autosomal dominant Alzheimer disease (ADAD) presenilin 1 (PSEN1) E280A variant had early life plasma biomarker findings consistent with amyloid β overproduction. However, the cognitive functioning of children with this variant has not been characterized vs those without the variant., Objective: To test whether cognitive functioning of children with and without the PSEN1 E280A variant in the same ADAD cohort differed by genetic status (ie, PSEN1 variant) and sex., Design, Setting, and Participants: This cohort study was conducted among 1354 children (including 265 children with the variant) aged 6 to 16 years recruited from the Alzheimer Prevention Initiative Colombia Registry. Participants from the city of Medellín and surrounding suburban areas traveled to the University of Antioquia to undergo all procedures. Participants were administered a Spanish version of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) to measure general cognitive functioning. Data were analyzed from July through November 2020., Main Outcomes and Measures: Univariate general linear models were used to characterize differences on WISC-IV cognitive performance by genetic status, sex, and the interaction of genetic status with sex. Urbanity, socioeconomic status, and education were entered as covariates., Results: Among 1354 children with ADAD (695 [51.3%] girls; mean [SD] age, 11.64 [2.64] years), there were 265 children with the variant (19.6%) and 1089 children without the variant (80.4%). Children with and without the variant did not differ by demographic variables or performance on WISC-IV indices. Irrespective of genetic status, boys had statistically significantly decreased mean scores on indices for working memory (90.27 [95% CI, 89.21-91.34] vs 92.99 [95% CI, 91.98-93.99]; mean difference = -2.72; P < .001), perceptual reasoning (91.56 [95% CI, 90.47-92.65] vs. 93.27 [95% CI, 91.23-94.30]; mean difference = -1.71; P = .03), and verbal comprehension (88.69 [95% CI, 87.54-89.84] vs. 90.81 [95% CI, 89.73-91.90]; mean difference = -2.12; P = .009) compared with girls. In the interaction between sex and genetic status, boys with the variant had worse mean working memory index performance (88.78 [95% CI, 86.86-90.70]) than girls with the variant (93.75 [95% CI, 91.95-95.55]; mean difference = -4.97; P = .001), as well as boys (91.77 [95% CI, 90.85-92.70]; mean difference = -2.99; P = .04) and girls (92.22 [95% CI, 91.32-93.13]; mean difference = -3.44; P = .009) without the variant., Conclusions and Relevance: This study found that boys with the PSEN1 variant had decreased working memory abilities compared with girls with the variant and boys and girls without the variant, suggesting a sex-specific genetic risk in early life cognitive performance among individuals with the PSEN1 variant. This increased risk of future cognitive difficulties among boys with the variant may have important downstream implications for learning and academic achievement and could be associated with sex differences seen in adulthood on episodic memory measures.

Importance: Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline., Objectives: To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline., Design, Setting, and Participants: We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline., Main Outcomes and Measures: Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline., Results: A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset., Conclusions and Relevance: Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment.

Previous dual task studies have demonstrated that patients with sporadic Alzheimer's disease (AD) are impaired in their ability to perform two tasks simultaneously compared with healthy controls, despite being able to successfully perform the tasks alone relatively well. Yet, it remains unclear what the earliest clinical manifestation of this dual task coordination deficit is. This study examined dual task abilities in individuals who are at risk of early-onset familial AD due to an E280A presenilin-1 mutation. Thirty-nine carriers of the gene mutation who did not meet the criteria for AD and 29 non-carrier healthy controls were asked to perform digit recall accompanied by a secondary tracking task. Individuals who were carriers of the genetic mutation demonstrated significantly higher dual task costs than healthy non-carriers. Dual task performance was found to be more sensitive to this very early stage of FAD than episodic memory measures. The findings support the notion that a deficit in the coordination mechanism of the central executive may be a pre-clinical marker for the early detection of AD due to the E280A presenilin-1 gene mutation.

Introduction: Mild cognitive impairment (MCI) is a clinical syndrome that presents with memory disorders, normal general cognition, and no compromise of activities of daily living or dementia. Its diagnosis has important clinical implications, since it behaves as a possible predictor of cognitive disorders that would suggest the onset of dementia. Amnestic-type MCI is considered to be a stage prior to Alzheimer-type dementia. The prevalence of MCI varies from 1-29% and the existence of this diagnosis implies a risk of presenting dementia at 12% per year., Aim: To establish the prevalence of amnestic-type MCI in a group of persons over the age of 50 years from the Valle de Aburra., Patients and Methods: The sample was made up of 848 participants of both genders, over 50 years old, who lived in the metropolitan area of Medellin and had different socioeconomic and educational levels. Amnestic MCI was diagnosed according to the criteria proposed by the American Academy of Neurology., Results: Prevalence of amnestic MCI was 9.7%, and was more predominant in males (p = 0.01) than in females. The prevalence was significantly lower in the group with more than 12 years of schooling (p < 0.05), and no significant differences in the prevalence were found in relation to age or economic status., Conclusion: The prevalence of amnestic MCI, 9.7%, found in our study is within the range reported by other researchers.

Introduction: As part of the normal ageing process, cognitive deterioration clearly takes place in memory, attention and the information processing speed (IPS). Among the intervention strategies commonly used, combined programmes like those involving memory and psychomotor skills have the greatest beneficial effects on cognition in the short and long term., Aim: To evaluate the effects of a combined memory and psychomotor training programme entitled 'Independence in Older age' (SIMA) on the cognitive performance of a population sample of healthy elderly adults., Subjects and Methods: A cross-sectional study was conducted on 95 elderly adults (49 in the intervention group and 46 in the control group) before and after a 20-session training programme. Both intergroup (intervention group versus control group) and intragroup (each group individually) cognitive performance was analysed. The two groups were paired by age, sex and schooling., Results: The intergroup analysis following the training showed statistically and clinically significant differences in two IPS variables: conflict and interference in the colour-word test, which had a size effect of -1.31 and -1.38, respectively; the performance of the group of trained elderly adults was better than that of the controls. Likewise, in the intragroup analysis significant differences were found in these two variables in the group that received the intervention, with a size effect of -1.27 and -1.15., Conclusion: Findings show positive effects of combined SIMA memory and psychomotor training, especially in selective attention and the IPS with a healthy elderly adult population.

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease that affects small vessels and presents with vascular episodes, neuropsychiatric disorders, migraine and cognitive impairment. The cognitive disorder varies according to the time elapsed since onset. It is a condition with a subcortical origin related to executive dysfunction, slowing, attention-related disorders and memory disorders., Aim: To define the cognitive characteristics in two neuropsychological evaluations of carriers of Notch3 gene mutations as compared to non-carriers belonging to Colombian families with CADASIL., Subjects and Methods: The study followed a longitudinal, retrospective design with 140 participants, including both carriers and non-carriers of the mutation. Cognitive performance was analysed by comparing the first and the last neuropsychological evaluation carried out on each subject at a four-year interval., Results: There were statistically significant differences (p < 0.05) between the two groups in the last evaluation, but only in some tests. Carriers and non-carriers did not display any significant changes between the first and the last evaluation., Conclusions: No differences were found between both groups in the two evaluations. Cognitive impairment is not observed with the passage of time in carriers, probably owing to the fact that most of them were young, asymptomatic subjects. We believe that four years' follow-up is not enough time to observe a significant progression in the alterations affecting the cognitive functions in carriers of mutations in the Notch3 gene, which causes CADASIL. We also consider that more sensitive cognitive tools are needed to perform the neuropsychological evaluation.

Few studies have examined the presence of linguistic deficits in the preclinical phase of Alzheimer's disease (AD). A total of 19 healthy carriers of the E280A presenilin-1 gene mutation in chromosome 14 and 21 noncarrier family members from Antioquia, Colombia, were administered a neurolinguistic evaluation of lexical-semantic processes. Both groups were similar in age, educational level, and gender. Carriers scored significantly lower than noncarriers on naming of famous faces. Cognitive changes in lexical-semantic tasks can be detected before the clinical diagnosis of probable familial AD, and a neurolinguistic evaluation may be a useful tool in the early clinical diagnosis of sporadic AD as well.

Introduction: Various neuropsychological studies have been conducted to determine the cognitive functioning of patients with Huntington s disease and their results have shown that the pattern of cognitive decline is thought to be typical of a frontal subcortical dementia., Objectives: To determine if significant differences exist between the cognitive performances of a group diagnosed with Huntington s disease and a group of healthy, at risk relatives on a series of neuropsychological tests, and to examine the extent to which the Huntington group s cognitive performance profile corresponds to frontal subcortical damage as reported in other studies., Patients and Methods: The sample was comprised of a group of 18 subjects with a clinical diagnosis of initial stage Huntington s disease and a group of 15 healthy relatives at risk for Huntington s disease. A battery of tests (the CERAD) and additional neuropsychological tests were administered to all subjects., Results: Compared to the at risk group, the Huntington s disease group scored significantly lower on 85.41% of the tests., Conclusions: The neuropsychological tests utilized in this study were useful to discriminate between diagnosed and at risk groups. The Huntington s disease group s global neuropsychological profile was similar to that of a frontal subcortical dementia in which the predominant features include executive functioning deficits, memory problems, visuo constructive alterations, attention deficits, verbal fluency problems and naming deficits.

The aim of this article was to analyze the prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) in Colombian "Paisa" children and adolescents. A randomized sample of 4- to 17-year-old children and adolescents--176 males and 154 females--was selected from schools in Manizales, Colombia. The diagnosis of ADHD was obtained using a semistructured psychiatric and neurological interview, medical histories revision, and neurological or psychiatric evaluations. Several rating scales and a neuropsychological assessment were administered in order to confirm the diagnosis. Children with Full Scale Intelligence Quotient (FSIQ) between 71 and 84 were recorded as having Borderline Intellectual Functioning (BIF), and those with a history of mild motor retardation, and/or Performance Intelligence Quotient (PIQ) lower than 71, were recorded as having a Developmental Coordination disorder (DCD), after confirmation by neurological and neuropsychological examinations. BIF and DCD children were excluded from the ADHD group. Total prevalence of ADHD adjusted by sex was 16.4% (males 19.8% and females 12.3%). Prevalence of clean ADHD cases was 11.5%, distributed as follows: combined type, 6.4%; inattentive, 4.8%; and hyperactive-impulsive, 0.3%. Distribution by sex was as follows: males, 14.8%; and females, 7.7%; with an odds ratio of 2.1 (95% CI: 1-4.5, chi 2 = 4.0, p < .05). Clean prevalence of ADHD adjusted by equal sex distribution was 11.3%. Prevalence of BIF was 5.8%, DCD 3.0%, and mild mental retardation 3.9%. Prevalence of ADHD did not show differences by socioeconomic status (SES), in contrast to mild mental retardation in which BIF and DCD were significantly more frequent in the lower SES.

Introduction: The department of Antioquia in Columbia is the main producer of gold in Columbia. In the gold-producing regions the population is exposed to high levels of mercury used in the processes of extraction and purification. Studies done in Columbia on neurotoxicity underline the hazards of mercury from the environmental and occupational-health point of view, but the effect of long-term exposure on cognitive function has not been studied., Objective: To determine whether the miners of El Bagre (Antioquia, Columbia) have neuropsychological and/or behavior disorders as a result of occupational exposure to toxic mercury vapor., Patients and Methods: The sample was made up of 22 right-handed men, residents of El Bagre, aged between 20 and 45 years old who had been exposed to mercury vapor for at least three years. The control group consisted of 22 men who lived in the non-mining regions of the department and had not been exposed to mercury, paired with the cases considered for age and educational status. Neuropsychological assessment, a medical examination and behavioral performance tests were applied to all the men (in both groups)., Results: In the study group alterations were seen and classified as: intellectual damage (mainly alteration of executive function and constructional praxis); emotional changes (symptoms of depression and anxiety) and neurological changes (amnesia, insomnia and tremor of the tongue). No changes were found in the control group., Conclusion: Exposure to mercury causes specific neuropsychological and behavior disorders in the absence of clinically detectable physical or physiological damage.

Introduction: Prevalence of late onset Alzheimer's disease (LOAD) both familial and sporadic is increasing with the raising proportion of third-age population. There are evidences either supporting or rejecting the existence of differences in the behavior of neuropsychological variables between familial and sporadic cases of LOAD., Objective: To identify neuropsychological variables discriminating between familial and sporadic cases of LOAD, in order to detect clinical manifestations that may provide information on the pathological process of the neurodegenerative process., Patients and Methods: Using sequential sampling, we selected individuals affected by LOAD according to the criteria of the DSM-IV and NINCS-ADRDA. The following neuropsychological protocol was used: CERAD, Wisconsin, Phonological Fluency, Rey's Figure, Raven, A Cancellation Test, WAIS (Arithmetic); also used were: Global Deterioration Scale, Functional Assessment Staging of Reisberg (FAST), Barthel and Yesavage. Parametrical and non-parametrical univariate, factorial (principal components) and discriminant analyses were performed. In total, 52 patients were analyzed (average age: 74.8 years; mean age at onset of the disease: 69 years; time of disease's evolution: 5.7 years; average of educational level: 6.4 years)., Results: No significant statistical differences were found in clinical or neuropsychological variables between familial and sporadic cases of LOAD. Additionally, neither variables nor models were detected discriminating significantly between them., Conclusion: Familial and sporadic cases of LOAD present the same clinical and neuropsychological phenotype which makes very probable that sporadic cases are low penetrance familial ones.

Few longitudinal studies have been carried out to investigate the cognitive decline in early onset of familial Alzheimer's disease (FAD). In this study 12 patients with FAD (M age = 49.61 years, SD = 4.99), 10 patients with sporadic Alzheimer's disease (SAD) (M age = 71.40, SD =10.00), and 15 matched normal controls (M age = 45.01, SD = 7.24) were selected. A comprehensive neuropsychological battery was administered three times over a period of 18 months. Individuals designated as FAD met the criteria for dementia and were positive for the E280A presenilin 1 mutation. Participants with SAD met the criteria for dementia and were negative for the E280A presenilin 1 mutation. Normal control participants were the FAD patients' relatives, who were negative for the mutation. Two groups of neuropsychological instruments were administered: (1) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery, and (2) additional neuropsychological tests of abstraction and constructional abilities. Patients with FAD were significantly impaired on all measures at the first examination except for reading of words. While the performance of the normal controls remained unchanged over the 18 months for most neuropsychological tests, the patients with FAD displayed a decline in verbal memory, language, constructional and abstraction tests. The greatest decline was observed on the Mini-Mental State Exam scores. Patients with SAD demonstrated a similar pattern of cognitive decline, but the decline was faster in FAD than in SAD participants.

We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

Objective Neuropsychiatric symptoms (NPS) are common clinical features of patients with Parkinson's disease (PD). However, such symptoms in non-demented PD patients have scarcely been investigated. To address this issue, we describe the neuropsychiatric profile in PD patients with and without Mild Cognitive Impairment (MCI). Participants and Method Eighty non-demented PD patients were included. The patients were divided into two groups depending on the presence or absence of MCI (PD-MCI and PD-nMCI, respectively). MCI diagnosis was made according to the Movement Disorder Society Task Force Level I criteria. NPS were evaluated using the Neuropsychiatric Inventory (NPI). For each domain, the presence and magnitude of symptoms (frequency x severity) was calculated. The total NPI score was also computed, in which higher scores suggest greater behavioral disturbance. Results PD-nMCI (n = 59, 74%) and PD-MCI (n = 21, 26%) groups were similar in the disease stage and years since diagnosis. In contrast with the PD-nMCI group, participants in the PD-MCI group were older. Fourteen PD-MCI (66%) and 45 PD-nMCI (76%) patients reported at least one neuropsychiatric symptom in the previous month. In both groups, the most frequent NPS were sleep disorders, depression, anxiety, apathy, irritability, and disinhibition. Additionally, the proportion of these symptoms between groups did not differ significantly (p > 0.05). There was only a tendency of greater score in the disinhibition subscale in PD-MCI group (p < 0.02). In both groups, NPS were not associated with clinical variables (years since diagnosis, Unified Parkinson's Disease Rating Scale -III) after adjusting for age. Conclusions Preliminary findings suggest that NPS are frequent in PD patients independent of the degree of cognitive impairment, and they may encompass non-motor features of the clinical spectrum of the disease. Further longitudinal investigations are needed to determine whether such symptoms may predict the cognitive decline in these patients. [ABSTRACT FROM AUTHOR]