Band separation and electric field prediction in square Bravais-Moiré photonic crystals.

In this study, we address three key challenges in photonic crystals: modeling of isolated flat bands, electric field prediction, and band separation in dispersion relations. Using twisted square Bravais lattices at specific angles, we create Bravais-Moiré photonic crystals exhibiting unique characteristics. These include band pairing and parallelism in certain Brillouin zones, enabling predictable electric field behavior and identification of isolated, flat band pairs within extensive band gaps. We apply advanced Shape theory-based classification methods for precise band separation, offering significant contributions to photonics research and light manipulation applications.

The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

Memory for Semantically Related Objects Differentiates Cognitively Unimpaired Autosomal Dominant Mutation Carriers from Non-Carrier Family Members.

Early cognitive changes due to Alzheimer's disease (AD) include difficulties in semantic access and working memory. Using a computerized cognitive test developed by our group, called the Memory for Semantically Related Objects test (MESERO), we evaluated if cognitively unimpaired carriers of an autosomal dominant AD (ADAD) mutation performed worse on this test than non-carrier family members. 35 cognitively unimpaired ADAD mutation carriers and 26 non-carrier family members from a Colombian ADAD cohort took the MESERO on a laptop computer. Cognitively unimpaired ADAD carriers had significantly worse MESERO total scores than non-carrier family members, driven by worse performance in semantically-related object sets; group performances did not differ on semantically unrelated object sets. Findings suggest that MESERO performance may be sensitive to subtle cognitive changes associated with AD. Future MESERO research should examine performances between healthy older adults and people at risk for sporadic AD.

APOE3 Christchurch modulates tau phosphorylation and ß-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases.

Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.

Nutritional Assessment in Patients with Early-Onset Autosomal Dominant Alzheimer's Disease Due to PSEN1- E280A Genetic Variant: A Cross-Sectional Study.

Background: Weight loss and malnutrition are frequent findings in late-onset and sporadic presentations of Alzheimer's Disease (AD). However, less is known about nutritional status in Early-Onset Autosomal Dominant AD (EO-ADAD). Objective: To analyze the association between nutritional status and other clinical and sociodemographic characteristics in individuals with a genetic form of EO-ADAD. Design settings and participants: Cross-sectional study with 75 non-institutionalized participants from a cohort of Autosomal Dominant AD (13 with mild cognitive impairment and 61 with dementia, ages from 38 to 67 years) underwent a structured clinical assessment with emphasis on nutritional status. Measurements: Primary outcome was nutritional status and it was measured using the Mini Nutritional Assessment (MNA). Patients were categorized according to MNA total score, as undernourished (MNA ≤23.5) and well-nourished (MNA ≥ 24). Sociodemographic and clinical variables identified as potential predictors or confounders of nutritional status were also collected. Results: Undernourishment by MNA was present in 57.3% of the sample. Forty-two percent of participants had abnormal BMI values considered lower than 18.5 or higher than 24.9 kg/m2. Total BMI values were similar in well and undernourished patients (median 24.2 IQR 3.59 and median 23.9 IQR 4.42, respectively, p=0.476). When comparing well and undernourished groups, we found statistically significant differences for variables: severity of dementia (p=0.034), frailty (p=0.001), multimorbidity (p=0.035) and, polymedication (p=0.045). Neither adjusted logistic regression nor the Poisson regression showed that any clinical or sociodemographic variables explained undernourishment. Conclusions: Undernourishment was a frequent finding in our sample of EO-ADAD, especially in later stages of the disease. Patients with polymedication, multimorbidity, frailty and severe dementia show differences in their nutritional status with a tendency to be more frequently undernourished. Further studies with larger sample sizes are needed to establish this association.

Analysis and evaluation of handwriting in patients with Parkinson's disease using kinematic, geometrical, and non-linear features.

BACKGROUND AND OBJECTIVES: Parkinson's disease is a neurological disorder that affects the motor system producing lack of coordination, resting tremor, and rigidity. Impairments in handwriting are among the main symptoms of the disease. Handwriting analysis can help in supporting the diagnosis and in monitoring the progress of the disease. This paper aims to evaluate the importance of different groups of features to model handwriting deficits that appear due to Parkinson's disease; and how those features are able to discriminate between Parkinson's disease patients and healthy subjects. METHODS: Features based on kinematic, geometrical and non-linear dynamics analyses were evaluated to classify Parkinson's disease and healthy subjects. Classifiers based on K-nearest neighbors, support vector machines, and random forest were considered. RESULTS: Accuracies of up to 93.1% were obtained in the classification of patients and healthy control subjects. A relevance analysis of the features indicated that those related to speed, acceleration, and pressure are the most discriminant. The automatic classification of patients in different stages of the disease shows κ indexes between 0.36 and 0.44. Accuracies of up to 83.3% were obtained in a different dataset used only for validation purposes. CONCLUSIONS: The results confirmed the negative impact of aging in the classification process when we considered different groups of healthy subjects. In addition, the results reported with the separate validation set comprise a step towards the development of automated tools to support the diagnosis process in clinical practice.

Biological and Cognitive Markers of Presenilin1 E280A Autosomal Dominant Alzheimer's Disease: A Comprehensive Review of the Colombian Kindred.

The study of individuals with autosomal dominant Alzheimer's disease affords one of the best opportunities to characterize the biological and cognitive changes of Alzheimer's disease that occur over the course of the preclinical and symptomatic stages. Unifying the knowledge gained from the past three decades of research in the world's largest single-mutation autosomal dominant Alzheimer's disease kindred - a family in Antioquia, Colombia with the E280A mutation in the Presenilin1 gene - will provide new directions for Alzheimer's research and a framework for generalizing the findings from this cohort to the more common sporadic form of Alzheimer's disease. As this specific mutation is virtually 100% penetrant for the development of the disease by midlife, we use a previously defined median age of onset for mild cognitive impairment for this cohort to examine the trajectory of the biological and cognitive markers of the disease as a function of the carriers' estimated years to clinical onset. Studies from this cohort suggest that structural and functional brain abnormalities - such as cortical thinning and hyperactivation in memory networks - as well as differences in biofluid and in vivo measurements of Alzheimer's-related pathological proteins distinguish Presenilin1 E280A mutation carriers from non-carriers as early as childhood, or approximately three decades before the median age of onset of clinical symptoms. We conclude our review with discussion on future directions for Alzheimer's disease research, with specific emphasis on ways to design studies that compare the generalizability of research in autosomal dominant Alzheimer's disease to the larger sporadic Alzheimer's disease population.

The Value of Pre-Screening in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease Trial.

The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-ß antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.

APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer's disease.

Alzheimer's disease (AD) age of onset (ADAOO) varies greatly between individuals, with unique causal mutations suggesting the role of modifying genetic and environmental interactions. We analyzed ~50 000 common and rare functional genomic variants from 71 individuals of the 'Paisa' pedigree, the world's largest pedigree segregating a severe form of early-onset AD, who were affected carriers of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gene. Affected carriers with ages at the extremes of the ADAOO distribution (30s-70s age range), and linear mixed-effects models were used to build single-locus regression models outlining the ADAOO. We identified the rs7412 (APOE*E2 allele) as a whole exome-wide ADAOO modifier that delays ADAOO by ~12 years (ß=11.74, 95% confidence interval (CI): 8.07-15.41, P=6.31 × 10(-8), PFDR=2.48 × 10(-3)). Subsequently, to evaluate comprehensively the APOE (apolipoprotein E) haplotype variants (E1/E2/E3/E4), the markers rs7412 and rs429358 were genotyped in 93 AD affected carriers of the E280A mutation. We found that the APOE*E2 allele, and not APOE*E4, modifies ADAOO in carriers of the E280A mutation (ß=8.24, 95% CI: 4.45-12.01, P=3.84 × 10(-5)). Exploratory linear mixed-effects multilocus analysis suggested that other functional variants harbored in genes involved in cell proliferation, protein degradation, apoptotic and immune dysregulation processes (i.e., GPR20, TRIM22, FCRL5, AOAH, PINLYP, IFI16, RC3H1 and DFNA5) might interact with the APOE*E2 allele. Interestingly, suggestive evidence as an ADAOO modifier was found for one of these variants (GPR20) in a set of patients with sporadic AD from the Paisa genetic isolate. This is the first study demonstrating that the APOE*E2 allele modifies the natural history of AD typified by the age of onset in E280A mutation carriers. To the best of our knowledge, this is the largest analyzed sample of patients with a unique mutation sharing uniform environment. Formal replication of our results in other populations and in other forms of AD will be crucial for prediction, follow-up and presumably developing new therapeutic strategies for patients either at risk or affected by AD.

Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate.

Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder.

Descripción genotípica y fenotípica de la enfermedad de Alzheimer tardía y familiar precoz: revisión / Genotypic and phenotypic description of late-onset Alzheimer's disease and early onset familial Alzheimer's: Review / Descrição genotípica e fenotípica da doença de Alzheimer tardia e familiar precoce: revisão

La demencia es la pérdida de varias áreas del funcionamiento cognitivo respecto al nivel premórbido, con deterioro significativo en la funcionalidad. La más común es ocasionada por la enfermedad de Alzheimer, que se define como un trastorno neurodegenerativo que produce una alteración progresiva de la memoria y de otras habilidades mentales, por una pérdida de volumen en los lóbulos temporales, en especial en las áreas mediales como el hipocampo y la corteza entorrinal. Menos del 5% de los pacientes con esta enfermedad presenta formas hereditarias que pueden tener un inicio precoz (antes de los 65 años) o tardío (después de dicha edad). La EA precoz presenta un patrón de herencia autosómico dominante y puede ser causado por mutaciones en el gen de la proteína precursora de amiloide, en presenilina-1 o presenilina-2. Los casos de EA tardía, están influenciados por una genética compleja, con múltiples factores de susceptibilidad y el alelo ApoE4 es el principal y más reconocido. La EA es una enfermedad heterogénea tanto en su genotipo como en su fenotipo que varían en cuanto a intensidad y tipo de síntomas, edad de inicio y severidad de la demencia, de acuerdo con las mutaciones que el paciente presenta y su interacción con factores ambientales.

Dementia is known as the loss of multiple areas of cognitive function with respect to a premorbid condition, involving a significant deterioration in functionality. The most common subtype is Alzheimer's disease, which is defined as a neurodegenerative disorder that causes a progressive deterioration in memory and other mental capacities due to volume loss in temporal lobes, especially in mesial aspects, such as the hippocampus and the entorhinal cortex. Approximately 5% of patients affected by this disease have a hereditary form, with an early onset (before 65 years) or a late onset (after 65 years). Early onset Alzheimer's disease has a genetic autosomal dominant inheritance pattern, which can be caused by mutations in the gene encoding for the amyloid precursor protein, presenilin-1, or presenilin-2. In the cases of late onset Alzheimer's disease, there is a complex genetic influence, with multiple susceptibility factors, where the ApoE4 allele is the main and most recognized factor. Alzheimer's disease is a heterogeneous dementia, both in genotype and phenotype, varying in intensity and symptoms, age of onset, and severity of the disease, depending on the different mutations that a patient may have and the interactions with environmental factors.

A demência é a perda de várias áreas do funcionamento cognitivo com respeito ao nível pré-mórbido, com deterioro significativo na funcionalidade. A mais comum é ocasionada pela doença de Alzheimer, que se define como um transtorno neurodegenerativo que produz uma alteração progressiva da memória e de outras habilidades mentais, por uma perda de volume nos lóbulos temporais, em especial nas áreas mediais como o hipocampo e o córtex entorrinal. Menos de 5% dos pacientes com esta doença apresenta formas hereditárias que podem ter um início precoce (antes dos 65 anos) ou tardio (depois de dita idade). A D.A. precoce apresenta um padrão de herança autossômico dominante e pode ser causado por mutações no gene da proteína precursora de amiloide, em presenilina-1 ou presenilina-2. Os casos de D.A. tardia, estão influenciados por uma genética complexa, com múltiplos fatores de susceptibilidade e o alelo ApoE4 é o principal e mais reconhecido. A D.A. é uma doença heterogénea tanto em seu genótipo como em seu fenótipo que variam em quanto a intensidade e tipo de sintomas, idade de inicio e severidade da demência, de acordo com as mutações que o paciente apresenta e sua interação com fatores ambientais.

Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

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.

Deciphering interference control in adults with ADHD by using distribution analyses and electromyographic activity.

A deficit in "interference control" is commonly found in adults with Attention Deficit Hyperactivity Disorder (ADHD). This has mainly been interpreted as difficulties in inhibiting inappropriate responses. However, interference control involves processes other than simply the ability to inhibit. Consequently, we used sophisticated analysis to decipher the additional processes of interference control in these patients. We compared interference control between 16 adults with ADHD and 15 control adults performing a Simon task. In most studies, performance is generally reported in terms of mean error rates and reaction times (RTs). However, here we used distribution analyses of behavioral data, complemented by analyses of electromyographic (EMG) activity. This allowed us to better quantify the control of interference, specifically the part that remains hidden when pure correct trials are not distinguished from partial errors. Partial errors correspond to sub-threshold EMG bursts induced by incorrect responses that immediately precede a correct response. Moreover, besides "online" control, we also investigated cognitive control effects manifesting across consecutive trials. The main findings were that adults with ADHD were slower and showed a larger interference effect in comparison to controls. However, the data revealed that the larger interference effect was due neither to higher impulse expression, nor to a deficit in inhibition but that these patients presented a larger interference effect than the controls after congruent trials. We propose and discuss the hypothesis that the interference control deficit found in adults with ADHD is secondary to impairments in sustained attention.

Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer's disease.

The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P=1.29 × 10⁻¹²; NPHP1, rs10173717, P=1.74 × 10⁻¹²; CADPS2, rs3757536, P=1.54 × 10⁻¹°; GREM2, rs12129547, P=1.69 × 10⁻¹³, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions.

A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD.

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10(-8)) and 11q and 17p (P<1 × 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.

Event-related potential markers of brain changes in preclinical familial Alzheimer disease.

OBJECTIVES: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45. METHODS: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded. RESULTS: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200-300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. CONCLUSIONS: Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD.

A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication.

Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.

Enfermedad periodontal como signo clínico precoz de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) / Periodontal disease as an early clinical sign of cerebral autosomal, dominant arteriopathy with subcortical, infarcts and leudoencephalopathy (CADASIL)

Introducción. Los signos clínicos de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) se expresan principalmente en el sistema nervioso y recientemente se han descrito en la retina. Objetivo. Establecer la prevalencia y el riesgo de enfermedad periodontal en sujetos de familias con historia de presencia de mutación CADASIL del departamento de Antioquia, Colombia. Sujetos y métodos. Se realizó un estudio transversal (crosssectional), con asignación al grupo CADASIL y grupo control según genotipificación de cada sujeto para la mutación R1031C y C455R en Notch3. Cada participante firmó voluntariamente el consentimiento informado y recibió evaluación clínica neurológica,neuropsicológica y periodontal. Resultados. No existieron diferencias significativas entre los dos grupos según edad, sexo, escolaridad, tabaquismo, estado cognitivo, estado funcional y presencia de dientes naturales. La frecuencia de placa blanda, gingivitis y enfermedad periodontal fue significativamente mayor en el grupo de portadores de mutación CADASILque en el grupo control. El grupo CADASIL presentó seis veces más riesgo de tener placa blanda mayor o igual al 20% que el grupo control. La prevalencia de gingivitis mayor o igual al 10% se presentó en el total de los integrantes del grupo CADASIL. Las personas que conformaron el grupo CADASIL presentaron cinco veces más riesgo de tener enfermedad periodontal que el grupo control. Conclusión. Las personas portadoras de mutación CADASIL presentan mayor prevalencia y riesgo de enfermedad periodontal (AU)

Introduction. The clinical signs of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are expressed mainly in the nervous system and recently reports also situate them in the retina. Aim. To determine the prevalence and risk of periodontal disease in subjects from families with a history of CADASIL mutation in the department of Antioquia, Colombia. Subjects and methods. A cross-sectional study was conducted, with subjects being assigned to the CADASIL group or a control group according to genotyping for the R1031C AND C455R mutation in Notch3. Each participant voluntarily signed the informed consent document and was submitted to neurological, neuropsychological and periodontal evaluation. Results. No significant differences were found between the two groups according to age, sex, schooling, tobacco smoking, cognitive status, functional status and the presence of natural teeth. The frequency of soft plaque, gingivitis and periodontal disease was significantly higher in the group of carriers of the CADASIL mutation than in the control group. The CADASIL group had six times more risk of having soft plaque above or equal to 20% than the control group. Prevalence of gingivitis above or equal to 10% was observed in all the members of the CADASIL group. The people in the CADASIL group had five times more risk of suffering periodontal disease than the control group. Conclusions. Carriers of the CADASIL mutation displayed a higher prevalence and risk of periodontal disease (AU)

[Periodontal disease as an early clinical sign of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)]. / Enfermedad periodontal como signo clínico precoz de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL).

INTRODUCTION: The clinical signs of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are expressed mainly in the nervous system and recently reports also situate them in the retina. AIM: To determine the prevalence and risk of periodontal disease in subjects from families with a history of CADASIL mutation in the department of Antioquia, Colombia. SUBJECTS AND METHODS: A cross-sectional study was conducted, with subjects being assigned to the CADASIL group or a control group according to genotyping for the R1031C and C455R mutation in Notch3. Each participant voluntarily signed the informed consent document and was submitted to neurological, neuropsychological and periodontal evaluation. RESULTS: No significant differences were found between the two groups according to age, sex, schooling, tobacco smoking, cognitive status, functional status and the presence of natural teeth. The frequency of soft plaque, gingivitis and periodontal disease was significantly higher in the group of carriers of the CADASIL mutation than in the control group. The CADASIL group had six times more risk of having soft plaque above or equal to 20% than the control group. Prevalence of gingivitis above or equal to 10% was observed in all the members of the CADASIL group. The people in the CADASIL group had five times more risk of suffering periodontal disease than the control group. CONCLUSIONS: Carriers of the CADASIL mutation displayed a higher prevalence and risk of periodontal disease.