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OBJECTIVES: Alzheimer's disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study, we examined the association between category fluency clustering performance (i.e., stating words sequentially that are all contained within a subcategory, such as domestic animals) and brain pathology in individuals with autosomal dominant Alzheimer's disease (ADAD). METHODS: A total of 29 non-demented carriers of the Presenilin1 E280A ADAD mutation and 32 noncarrier family members completed the category fluency test (Animals) and the Mini-Mental State Examination (MMSE). The participants also underwent positron emission tomography (PET) scans to evaluate in vivo amyloid-beta in the neocortex and tau in medial temporal lobe regions. Differences between carriers and noncarriers on cognitive tests were assessed with Mann-Whitney tests; associations between cognitive test performance and brain pathology were assessed with Spearman correlations. RESULTS: Animal fluency scores did not differ between carriers and noncarriers. Carriers, however, showed a stronger association between animal fluency clustering and in vivo AD brain pathology (neocortical amyloid and entorhinal tau) relative to noncarriers. CONCLUSION: This study indicates that using category fluency clustering, but not total score, is related to AD pathophysiology in the preclinical and early stages of the disease.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Encéfalo/patologia , Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Tomografia por Emissão de Pósitrons , Proteínas tau/genética , Disfunção Cognitiva/patologiaRESUMO
INTRODUCTION: This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer's disease (AD). METHODS: Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination. RESULTS: Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter. DISCUSSION: Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials. HIGHLIGHTS: Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations Cases had corticospinal tract microgliosis and severe Aß pathology in motor cortex There was no evidence of amyloid deposition in the spinal cord white matter All the neuropathology images are available for online visualization Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.
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OBJECTIVE: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance. METHODS: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. RESULTS: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. CONCLUSIONS: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/complicações , Disfunção Cognitiva/psicologia , Estudos de Coortes , Colômbia , Feminino , Heterozigoto , Humanos , Masculino , Testes Neuropsicológicos , Fatores SexuaisRESUMO
INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.
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Doença de Alzheimer , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/metabolismo , Cognição , Colômbia , Testes Neuropsicológicos , Presenilina-1/genética , Caracteres SexuaisRESUMO
BACKGROUND: Dysarthric symptoms in Parkinson's disease (PD) vary greatly across cohorts. Abundant research suggests that such heterogeneity could reflect subject-level and task-related cognitive factors. However, the interplay of these variables during motor speech remains underexplored, let alone by administering validated materials to carefully matched samples with varying cognitive profiles and combining automated tools with machine learning methods. OBJECTIVE: We aimed to identify which speech dimensions best identify patients with PD in cognitively heterogeneous, cognitively preserved, and cognitively impaired groups through tasks with low (reading) and high (retelling) processing demands. METHODS: We used support vector machines to analyze prosodic, articulatory, and phonemic identifiability features. Patient groups were compared with healthy control subjects and against each other in both tasks, using each measure separately and in combination. RESULTS: Relative to control subjects, patients in cognitively heterogeneous and cognitively preserved groups were best discriminated by combined dysarthric signs during reading (accuracy = 84% and 80.2%). Conversely, patients with cognitive impairment were maximally discriminated from control subjects when considering phonemic identifiability during retelling (accuracy = 86.9%). This same pattern maximally distinguished between cognitively spared and impaired patients (accuracy = 72.1%). Also, cognitive (executive) symptom severity was predicted by prosody in cognitively preserved patients and by phonemic identifiability in cognitively heterogeneous and impaired groups. No measure predicted overall motor dysfunction in any group. CONCLUSIONS: Predominant dysarthric symptoms appear to be best captured through undemanding tasks in cognitively heterogeneous and preserved cohorts and through cognitively loaded tasks in patients with cognitive impairment. Further applications of this framework could enhance dysarthria assessments in PD. © 2021 International Parkinson and Movement Disorder Society.
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Disfunção Cognitiva , Doença de Parkinson , Cognição , Disartria/diagnóstico , Disartria/etiologia , Humanos , Aprendizado de Máquina , FalaRESUMO
OBJECTIVE: Visual memory (ViM) declines early in Alzheimer's disease (AD). However, it is unclear whether ViM impairment is evident in the preclinical stage and relates to markers of AD pathology. We examined the relationship between ViM performance and in vivo markers of brain pathology in individuals with autosomal dominant AD (ADAD). METHODS: Forty-five cognitively unimpaired individuals from a Colombian kindred with the Presenilin 1 (PSEN1) E280A ADAD mutation (19 carriers and 26 noncarriers) completed the Rey-Osterrieth Complex Figure immediate recall test, a measure of ViM. Cortical amyloid burden and regional tau deposition in the entorhinal cortex (EC) and inferior temporal cortex (IT) were measured using 11C-Pittsburgh compound B positron emission tomography (PET) and 11F-flortaucipir PET, respectively. RESULTS: Cognitively unimpaired carriers and noncarriers did not differ on ViM performance. Compared to noncarriers, carriers had higher levels of cortical amyloid and regional tau in both the EC and IT. In cognitively unimpaired carriers, greater cortical amyloid burden, higher levels of regional tau, and greater age were associated with worse ViM performance. Only a moderate correlation between regional tau and ViM performance remained after adjusting for verbal memory scores. None of these correlations were observed in noncarriers. CONCLUSIONS: Results suggest that AD pathology and greater age are associated with worse ViM performance in ADAD before the onset of clinical symptoms. Further investigation with larger samples and longitudinal follow-up is needed to examine the utility of ViM measures for identifying individuals at high risk of developing dementia later in life.
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Doença de Alzheimer , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Amiloide , Peptídeos beta-Amiloides , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Presenilina-1/genética , Proteínas tauRESUMO
INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.
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Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Cognição/fisiologia , Mutação , Presenilina-1/genética , Adulto , Doença de Alzheimer/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
OBJECTIVES: The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease. METHODS: We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls. Moreover, to detect sui generis language disturbances, we ran analysis of covariance tests using executive functions as covariate. RESULTS: The two clinical groups showed impairments in all measures, most of which survived covariation with executive functions. However, the key finding concerned asymptomatic mutation carriers. While these subjects showed intact executive, semantic, and action-verb production skills, they evinced deficits in a syntactic test with minimal working memory load. CONCLUSIONS: We propose that this sui generis disturbance may constitute a prodromal sign anticipating eventual development of PD. Moreover, our results suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. (JINS, 2017, 23, 150-158).
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Transtornos da Linguagem/etiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Mutação/genética , Doença de Parkinson , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Função Executiva/fisiologia , Feminino , Humanos , Transtornos da Linguagem/genética , Linguística , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , SemânticaRESUMO
Assessments of action semantics consistently reveal markers of Parkinson's disease (PD). However, neurophysiological signatures of the domain remain under-examined in this population, especially under conditions that allow patients to process stimuli without stringent time constraints. Here we assessed event-related potentials and time-frequency modulations in healthy individuals (HPs) and PD patients during a delayed-response semantic judgment task involving related and unrelated action-picture pairs. Both groups had shorter response times for related than for unrelated trials, but they exhibited discrepant electrophysiological patterns. HPs presented significantly greater N400 amplitudes as well as theta enhancement and mu desynchronization for unrelated relative to related trials. Conversely, N400 and theta modulations were abolished in the patients, who further exhibited a contralateralized cluster in the mu range. None of these patterns were associated with the participants' cognitive status. Our results suggest that PD involves multidimensional neurophysiological disruptions during action-concept processing, even under task conditions that elicit canonical behavioral effects. New constraints thus emerge for translational neurocognitive models of the disease.
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Doença de Parkinson , Semântica , Humanos , Masculino , Feminino , Potenciais Evocados/fisiologia , Eletroencefalografia , Doença de Parkinson/psicologia , Tempo de Reação/fisiologiaRESUMO
INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Qualidade de Vida/psicologia , Testes Neuropsicológicos , Disfunção Cognitiva/etiologia , Cognição , ComunicaçãoRESUMO
OBJECTIVE: This study aims 1) To analyse differences in resting-state electroencephalogram (rs-EEG) spectral features of Parkinson's Disease (PD) and healthy subjects (non-PD) using Functional Data Analysis (FDA) and 2) To explore, in four independent cohorts, the external validity and reproducibility of the findings using both epoch-to-epoch FDA and averaged-epochs approach. METHODS: We included 169 subjects (85 non-PD; 84 PD) from four centres. Rs-EEG signals were preprocessed with a combination of automated pipelines. Sensor-level relative power spectral density (PSD), dominant frequency (DF), and DF variability (DFV) features were extracted. Differences in each feature were compared between PD and non-PD on averaged epochs and using FDA to model the epoch-to-epoch change of each feature. RESULTS: For averaged epochs, significantly higher theta relative PSD in PD was found across all datasets. Also, higher pre-alpha relative PSD was observed in three of four datasets in PD patients. For FDA, similar findings were achieved in theta, but all datasets showed consistently significant posterior pre-alpha differences across multiple epochs. CONCLUSIONS: Increased generalised theta, with posterior pre-alpha relative PSD, was the most reproducible finding in PD. SIGNIFICANCE: Rs-EEG theta and pre-alpha findings are generalisable in PD. FDA constitutes a reliable and powerful tool to analyse epoch-to-epoch the rs-EEG.
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Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Reprodutibilidade dos Testes , EletroencefalografiaRESUMO
We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.
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Doença de Alzheimer , Animais , Feminino , Humanos , Masculino , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Heterozigoto , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transdução de SinaisRESUMO
Action-concept outcomes are useful targets to identify Parkinson's disease (PD) patients and differentiate between those with and without mild cognitive impairment (PD-MCI, PD-nMCI). Yet, most approaches employ burdensome examiner-dependent tasks, limiting their utility. We introduce a framework capturing action-concept markers automatically in natural speech. Patients from both subgroups and controls retold an action-laden and a non-action-laden text (AT, nAT). In each retelling, we weighed action and non-action concepts through our automated Proximity-to-Reference-Semantic-Field (P-RSF) metric, for analysis via ANCOVAs (controlling for cognitive dysfunction) and support vector machines. Patients were differentiated from controls based on AT (but not nAT) P-RSF scores. The same occurred in PD-nMCI patients. Conversely, PD-MCI patients exhibited reduced P-RSF scores for both texts. Direct discrimination between patient subgroups was not systematic, but it yielded best outcomes via AT scores. Our approach outperformed classifiers based on corpus-derived embeddings. This framework opens scalable avenues to support PD diagnosis and phenotyping.
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BACKGROUND: Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer's disease and vascular dementia. OBJECTIVE: Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer's disease and vascular dementia. METHODS: We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer's disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. RESULTS: In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (Bâ=â-0.06, pâ<â0.05) and an increased severity of cerebral microbleeds (Bâ=â0.13, pâ<â0.001), lacunes (Bâ=â0.30, pâ<â0.001), and perivascular space enlargement in the basal ganglia (Bâ=â0.50, pâ<â0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (Bâ=â0.06, pâ<â0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. CONCLUSION: Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks.
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Doença de Alzheimer , Encéfalo , Demência Vascular , Presenilina-1/genética , Receptor Notch3/genética , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Colômbia/epidemiologia , Demência Vascular/diagnóstico , Demência Vascular/epidemiologia , Demência Vascular/genética , Demência Vascular/prevenção & controle , Diagnóstico Precoce , Família , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Serviços Preventivos de Saúde/métodos , Fatores de Risco , Comportamento de Redução do RiscoRESUMO
BACKGROUND: Greater neuroticism has been associated with higher risk for Alzheimer's disease (AD) dementia. However, the directionality of this association is unclear. We examined whether personality traits differ between cognitively-unimpaired carriers of autosomal-dominant AD (ADAD) and non-carriers, and are associated with in vivo AD pathology. OBJECTIVE: To determine whether personality traits differ between cognitively unimpaired ADAD mutation carriers and non-carriers, and whether the traits are related to age and AD biomarkers. METHODS: A total of 33 cognitively-unimpaired Presenilin-1 E280A mutation carriers and 41 non-carriers (ages 27-46) completed neuropsychological testing and the NEO Five-Factor Personality Inventory. A subsample (nâ=â46; 20 carriers) also underwent tau and amyloid PET imaging. RESULTS: Carriers reported higher neuroticism relative to non-carriers, although this difference was not significant after controlling for sex. Neuroticism was positively correlated with entorhinal tau levels only in carriers, but not with amyloid levels. CONCLUSION: The finding of higher neuroticism in carriers and the association of this trait with tau pathology in preclinical stages of AD highlights the importance of including personality measures in the evaluation of individuals at increased risk for cognitive impairment and dementia. Further research is needed to characterize the mechanisms of these relationships.
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Doença de Alzheimer , Neuroticismo , Presenilina-1/genética , Sintomas Prodrômicos , Proteínas tau/metabolismo , Adulto , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Mutação/genética , Testes Neuropsicológicos/estatística & dados numéricos , Testes de Personalidade/estatística & dados numéricos , Tomografia por Emissão de PósitronsRESUMO
Histopathological reports suggest that subregions of the thalamus, which regulates multiple physiological and cognitive processes, are not uniformly affected by Alzheimer's disease. Despite this, structural neuroimaging studies often consider the thalamus as a single region. Identification of in vivo Alzheimer's-dependent volumetric changes in thalamic subregions may aid the characterization of early nuclei-specific neurodegeneration in Alzheimer's disease. Here, we leveraged access to the largest single-mutation cohort of autosomal-dominant Alzheimer's disease to test whether cross-sectional abnormalities in subregional thalamic volumes are evident in non-demented mutation carriers (n = 31), compared to non-carriers (n = 36), and whether subregional thalamic volume is associated with age, markers of brain pathology and cognitive performance. Using automatic parcellation we examined the thalamus in six subregions (anterior, lateral, ventral, intralaminar, medial, and posterior) and their relation to age and brain pathology (amyloid and tau), as measured by PET imaging. No between-group differences were observed in the volume of the thalamic subregions. In carriers, lower volume in the medial subregion was related to increased cortical amyloid and entorhinal tau burden. These findings suggest that thalamic Alzheimer's-related volumetric reductions are not uniform even in preclinical and prodromal stages of autosomal-dominant Alzheimer's disease and therefore, this structure should not be considered as a single, unitary structure in Alzheimer's disease research.
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OBJECTIVE: To determine possible associations of hemispheric-regional alpha/theta ratio (α/θ) with neuropsychological test performance in Parkinson's Disease (PD) non-demented patients. METHODS: 36 PD were matched to 36 Healthy Controls (HC). The α/θ in eight hemispheric regions was computed from the relative power spectral density of the resting-state quantitative electroencephalogram (qEEG). Correlations between α/θ and performance in several neuropsychological tests were conducted, significant findings were included in a moderation analysis. RESULTS: The α/θ in all regions was lower in PD than in HC, with larger effect sizes in the posterior regions. Right parietal, and right and left occipital α/θ had significant positive correlations with performance in Judgement of Line Orientation Test (JLOT) in PD. Adjusted moderation analysis indicated that right, but not left, occipital α/θ influenced the JLOT performance related to PD. CONCLUSIONS: Reduction of the occipital α/θ, in particular on the right side, was associated with visuospatial performance impairment in PD. SIGNIFICANCE: Visuospatial impairment in PD, which is highly correlated with the subsequent development of dementia, is reflected in α/θ in the right posterior regions. The right occipital α/θ may represent a useful qEEG marker for evaluating the presence of early signs of cognitive decline in PD and the subsequent risk of dementia.
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Ritmo alfa/fisiologia , Testes Neuropsicológicos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/psicologia , Descanso/fisiologia , Ritmo Teta/fisiologia , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Estudos Transversais , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/fisiopatologia , Doença de Parkinson/diagnóstico , Descanso/psicologiaRESUMO
INTRODUCTION: Mild Cognitive Impairment (MCI) is common in Parkinson's Disease (PD). Few studies have compared the Health-Related Quality of Life (HRQoL) in patients with and without MCI due to PD (PD-MCI), and its correlation to patients' subjective cognitive and communicative difficulties has not been explored. OBJECTIVE: We aimed to compare HRQoL in PD-MCI and PD without MCI (PD-nMCI), and explore its possible relationship to subjective cognitive and communicative complaints. METHODS: We included 29 PD-nMCI and 11 PD-MCI patients. The HRQoL was assessed with the Parkinson's Disease Questionnaire-39 (PDQ-39): its Cognition dimension was used as a measure of subjective cognitive complaints, its Communication dimension for subjective communicative complaints, and the summary index (PDQ-39 SI) as an indicator of HRQoL. Non-parametric partial correlations between the Cognition and Communication dimensions, and the adjusted PDQ-39 SI were conducted. RESULTS: PD-MCI patients had greater subjective cognitive and communicative complaints and worse HRQoL than PD-nMCI patients. In the PD-MCI group, both subjective cognitive and communicative complaints exhibited significant direct correlations with the adjusted HRQoL scores. CONCLUSIONS: HRQoL seems to be affected in PD-MCI, and it might be influenced by greater subjective cognitive and communicative complaints. Including patient-reported outcome measures of HRQoL, and providing cognitive and speech rehabilitation, as well as psychotherapeutic strategies to face these deficits can enhance the patient-centred approach in PD.
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Neuropsychologists continue to face challenges when assessing Spanish-speaking individuals due to limited availability of normative data. We developed comprehensive normative data stratified by age and education for a Spanish neuropsychological test battery used by the Grupo de Neurociencias de Antioquia (Colombia) and the Colombian Alzheimer's Prevention Initiative Registry, which have followed large families at risk for autosomal-dominant Alzheimer's disease (ADAD) since the 1990s. Approximately 75% of these individuals are cognitively-unimpaired and are not genetically predisposed to develop ADAD. We conducted a retrospective study on neuropsychological evaluations from 2,673 cognitively unimpaired individuals (56% female), with ages ranging from 18 to 86 years and education from 1 to 25 years. Neuropsychological measures included the Consortium to Establish a Registry for Alzheimer's Disease-Colombia, and other multidomain Spanish tests. We examined associations between age, education, and sex with cognitive performance. Norms stratified by age and education are presented. Cognitive performance showed small associations with age and education and was unrelated to sex. We provided population-based norms for Spanish tests targeting multiple cognitive domains using a large Colombian sample. These normative data may be helpful for the neuropsychological characterization of Spanish speakers from Latin America in clinical and research settings.
Assuntos
Doença de Alzheimer , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Colômbia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valores de Referência , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: In contrast to sporadic Alzheimer's disease, autosomal dominant Alzheimer's disease (ADAD) is associated with greater neuropathological evidence of cerebellar amyloid plaque (Aß) deposition. In this study, we used positron emission tomography (PET) measurements of fibrillar Aß burden to characterize the presence and age at onset of cerebellar Aß deposition in cognitively unimpaired (CU) Presenilin-1 (PSEN1) E280A mutation carriers from the world's largest extended family with ADAD. METHODS: 18F florbetapir and 11C Pittsburgh compound B (PiB) PET data from two independent studies - API ADAD Colombia Trial (NCT01998841) and Colombia-Boston (COLBOS) longitudinal biomarker study were included. The tracers were selected independently by the respective sponsors prior to the start of each study and used exclusively throughout. Template-based cerebellar Aß-SUVR (standard-uptake value ratios) using a known-to-be-spared pons reference region (cerebellar SUVR_pons), to a) compare 28-56-year-old CU carriers and non-carriers; b) estimate the age at which cerebellar SUVR_pons began to differ significantly in carrier and non-carrier groups; and c) characterize in carriers associations with age, cortical SUVR_pons, delayed recall memory, and API ADAD composite score. RESULTS: Florbetapir and PiB cerebellar SUVR_pons were significantly higher in carriers than non-carriers (p < 0.0001). Cerebellar SUVR_pons began to distinguish carriers from non-carriers at age 34, 10 years before the carriers' estimated age at mild cognitive impairment onset. Florbetapir and PiB cerebellar SUVR_pons in carriers were positively correlated with age (r = 0.44 & 0.69, p < 0.001), cortical SUVR_pons (r = 0.55 & 0.69, p < 0.001), and negatively correlated with delayed recall memory (r = -0.21 & -0.50, p < 0.05, unadjusted for cortical SUVR_pons) and API ADAD composite (r = -0.25, p < 0.01, unadjusted for cortical SUVR_pons in florbetapir API ADAD cohort). CONCLUSION: This PET study provides evidence of cerebellar Aß plaque deposition in CU carriers starting about a decade before the clinical onset of ADAD. Additional studies are needed to clarify the impact of using a cerebellar versus pons reference region on the power to detect and track ADAD changes, even in preclinical stages of this disorder.