PLA2G6 Mutations Related to Distinct Phenotypes: A New Case with Early-onset Parkinsonism

Background: PLA2G6-associated neurodegeneration (PLAN) is a recessive neurodegenerative disorder characterized by three distinct phenotypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (atypical NAD), and PLA2G6-related dystonia–parkinsonism. Methods: A consanguineous index case from Turkey was diagnosed with early-onset Parkinsonism at the Istanbul Faculty of Medicine. She and her unaffected brother were subjected to whole-genome sequencing. Results: In this report, we describe a 33-year-old index case with parental consanguinity and early-onset Parkinsonism. Whole-genome sequencing of this individual revealed that a homozygous p.R747W mutation in PLA2G6 segregates with the disease in this family Discussion: This result supports the importance of prioritizing this gene in mutational analysis of autosomal recessive Parkinsonism, and confirms the clinical heterogeneity of PLAN

Brain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2

BackgroundIn preclinical Alzheimer's disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions.MethodsWe tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol.ResultsIn asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Ass42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs.ConclusionsThese data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline

Normative data for the Turkish version of the pyramids and palm trees test

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Salience network engagement with the detection of morally laden information

Moral cognition is associated with activation of the default network, regions implicated in mentalizing about one's own actions or the intentions of others. Yet little is known about the initial detection of moral information. We examined the neural correlates of moral processing during a narrative completion task, which included an implicit moral salience manipulation. During fMRI scanning, participants read a brief vignette and selected the most semantically congruent sentence from two options to complete the narrative. The options were immoral, moral or neutral statements. RT was fastest for the selection of neutral statements and slowest for immoral statements. Neuroimaging analyses revealed that responses involving morally laden content engaged default and executive control network brain regions including medial and rostral prefrontal cortex, and core regions of the salience network, including anterior insula and dorsal anterior cingulate. Immoral moral conditions additionally engaged the salience network. These results implicate the salience network in the detection of moral information, which may modulate downstream default and frontal control network interactions in the service of complex moral reasoning and decision-making processes. These findings suggest that moral cognition involves both bottom-up and top-down attentional processes, mediated by discrete large-scale brain networks and their interactions

Episodic Memory and Metamemory in Parkinson's Disease Patients

This study investigated episodic memory and metamemory for verbs and nouns in patients who have cognitive impairments associated with Parkinson's disease (PD). PD patients and healthy control participants were asked to recall word pairs and provide feeling-of-knowing (FOK) judgments for the items they were unable to recall. This was followed by a 4-alternative recognition test. PD patients were impaired in both recall and recognition, compared with controls. In terms of metamemory, PD patients were less confident in their ability to recognize the unrecalled items in a future recognition test. Most important, accuracy of PD patients' FOK judgments was not above chance and was lower than that of control participants. The PD group correctly recognized fewer verbs than nouns, but type of material (verb vs. noun) had no impact on recall or FOK judgments. In addition, contribution of executive functions to FOK accuracy was different in PD patients and controls

Akinetic Mutism Without a Structural Prefrontal Lesion

Akinetic mutism is characterized by profound apathy and a lack of verbal and motor output for action, despite preserved alertness. The condition usually follows bilateral damage to the medial frontal subcortical circuits. We report a 59-year-old right-handed woman who was admitted to the neurology ward with sudden-onset akinetic mutism. Her medical history included an ischemic stroke 3 years earlier, with residual anomia and mild agraphia but no motor dysfunction. On this admission, a cranial computed tomography scan disclosed an acute left superior cerebellar infarction embracing the vermis, and a prior left inferior parietal infarct. Electroencephalogram showed bilateral frontal delta-wave activity. Four weeks later, we performed a technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (Tc-99m-HMPAO SPECT) scan to study the patient's frontal lobe function. The SPECT scan revealed the causative bifrontal hypoperfusion, more prominent on the right, while the structurally evident cerebellar infarction was predictably masked by subacute hyperperfusion phenomenon. Contralateral frontal diaschisis is an established sequela of cerebellar infarction. Because this patient also had lesions in the left parietal region, her left prefrontal area was critically deprived of its major reciprocally connected cortical counterparts (right prefrontal and left parietal), and also became dysfunctional. Her resulting bilateral frontal dysfunction is a common cause of akinetic mutism