Meta-analysis of the endogenous N200 latency event-related potential subcomponent in patients with Alzheimer’s disease and mild cognitive impairment

ObjectivesThe N200 latency subcomponent has the potential to be an accurate neurophysiological marker of the cognitive deterioration seen in Alzheimer’s disease (AD) and mild cognitive impairment (MCI).MethodsStandard mean difference (SMD) estimates of the N200 latency subcomponent were compared in three treatment groups: patients with AD, patients with MCI, and an unrelated elderly control group.ResultsPatients with AD had significantly prolonged N200 latencies compared to the control group, pooled SMD: 0.866 (95% CI: 0.517 to 1.214, z = 4.87, p < 0.001). Patients with MCI had significantly prolonged N200 latencies compared to the control group, pooled SMD: 0.578 (95% CI: 0.213 to 0.943, z = 3.31, p = 0.002). When comparing patients with AD and MCI the N200 latencies were similar, pooled SMD: 0.096 (95% CI: −0.261 to 0.453, z = 0.53, p = 0.598).ConclusionThe abnormalities present in the N200 latency subcomponent validate previous research that N200 latency is an informative indicator of information-processing deterioration in patients with cognitive impairment.SignificanceClinically, measurements of N200 latency can be used as a risk assessment of elderly patients that may be progressing to mild cognitive impairment and/or Alzheimer’s disease.     

Attention,vigilance and visuospatial function in hospitalized elderly medical patients: Relationship to neurocognitive diagnosis

ObjectiveEfficient detection of neurocognitive disorders is a key diagnostic challenge. We explored how simple bedside tests of attention, vigilance and visuospatial function might assist in identifying delirium in hospitalized patients.MethodsPerformance on a battery of bedside cognitive tests was compared in elderly medical inpatients with DSM-IV delirium, dementia, comorbid delirium-dementia, and no neurocognitive disorder.Results193 patients [mean age 79.9 ± 7.3; 97 male] were assessed with delirium (n = 45), dementia (n = 33), comorbid delirium-dementia (n = 65) and no neurocognitive disorder (NNCD) (n = 50). The ability to meaningfully engage with the tests varied from 84% (Spatial Span Forwards) to 57% (Vigilance B test), and was especially problematic among the comorbid delirium-dementia group. The NNCD was distinguished from the delirium groups for most tests, and from the dementia group for the Vigilance B test and the Clock Drawing Test. The dementia group differed from delirium groups in respect of the Months Backward Test, Vigilance A and B tests, Global assessment of visuospatial ability and the Interlocking Pentagons Test. Overall, patients with delirium were best identified by three tests – the Months Backward Test, Vigilance A test and the Global Assessment of visuospatial function with failure to correctly complete any two of these predicting delirium status in 80% of cases.ConclusionSimple bedside tests of attention, vigilance and visuospatial ability can help to distinguish neurocognitive disorders, including delirium, from other presentations. There is a need to develop more accurate methods specifically designed to assess patients with neurocognitive disorder who are unable to engage with conventional tests.     

Increased clinical and neurocognitive impairment in children with autism spectrum disorders and comorbid bipolar disorder

Bipolar (BD) symptomatology is prevalent in children with autism spectrum disorders (ASD) and may lead to increased impairment. The current study compared clinical and neurocognitive impairment in children (7–13 years) diagnosed with ASD (n = 55), BD (n = 34), ASD + BD (n = 23), and a non-clinical control group (n = 27). Relative to the ASD group, the ASD + BD group reported elevated rates of aggression and delinquency, behavioral disorders, depression, obsessive-compulsive disorder, and suicidal ideation, and poorer performance on the Stroop Color-Word Test. Future research might address how best to improve diagnostic assessment and adapt treatment to meet the needs of this uniquely impaired population.     

A longitudinal study of neurocognitive function in individuals at-risk for psychosis

IntroductionClinically defined prodromal diagnostic criteria identify at-risk individuals with a 35–40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established.MethodsA comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed.ResultsAt-risk subjects performed more poorly than healthy subjects (t = 2.93, P = 0.01), but better than first episode subjects (t = 4.72, p < 0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N = 11; z = − 1.2), while those at-risk subjects who did not progress to psychosis (N = 17) performed better (z = − 0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis.ConclusionNeurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.     

Expression of inducible nitric oxide synthase (iNOS) and period 1 (PER1) clock gene products in different sleep stages of patients with cognitive impairment

Circadian and sleep disturbances are common behavioural and psychological symptoms of dementia; circadian rhythm–related molecules may be altered in dementia patients. This study investigated the expression of the period 1 clock gene product (PER1), which is involved in circadian rhythms, and inducible nitric oxide synthase (iNOS), thought to generate nitric oxide, important in rapid eye movement (REM) sleep regulation. Specifically, we investigated the difference in expression of these two genes between patients with cognitive impairment and controls. We studied iNOS and PER1 mRNA expression using real-time polymerase chain reaction in peripheral leukocytes during REM sleep, non-REM sleep and wake stages in patients with Alzheimer’s disease (AD, n = 5), patients with mild cognitive impairment (MCI, n = 8) and controls (n = 9) during polysomnography examination. Expression of iNOS significantly increased during REM sleep in AD patients compared to MCI patients and controls. There were no significant differences in PER1 expression between the three groups, but an increase in PER1 expression during the wake stage was observed for all participants. Increased expression of iNOS during REM sleep of patients with AD might be a compensation mechanism for maintaining REM sleep. However, the precise role of nocturnal expression of iNOS in patients with AD requires further investigation.     

EEG microstates associated with salience and frontoparietal networks in frontotemporal dementia,schizophrenia and Alzheimer’s disease

ObjectiveThere are relevant links between resting-state fMRI networks, EEG microstate classes and psychopathological alterations in mental disorders associated with frontal lobe dysfunction. We hypothesized that a certain microstate class, labeled C and correlated with the salience network, was impaired early in frontotemporal dementia (FTD), and that microstate class D, correlated with the frontoparietal network, was impaired in schizophrenia.MethodsWe measured resting EEG microstate parameters in patients with mild FTD (n = 18), schizophrenia (n = 20), mild Alzheimer’s disease (AD; n = 19) and age-matched controls (old n = 19, young n = 18) to investigate neuronal dynamics at the whole-brain level.ResultsThe duration of class C was significantly shorter in FTD than in controls and AD, and the duration of class D was significantly shorter in schizophrenia than in controls, FTD and AD. Transition analysis showed a reversed sequence of activation of classes C and D in FTD and schizophrenia patients compared with that in controls, with controls preferring transitions from C to D, and patients preferring D to C.ConclusionThe duration and sequence of EEG microstates reflect specific aberrations of frontal lobe functions in FTD and schizophrenia.SignificanceThis study highlights the importance of subsecond brain dynamics for understanding of psychiatric disorders.     

Gender differences of neurocognitive functioning in patients with first-episode schizophrenia in China

AimsTo investigate the gender differences in neurocognitive functioning in patients with first-episode schizophrenia (FES) in China.MethodsA total of 449 Chinese patients with FES (210 males, 239 females) were included in this study. Participants’ psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Neurocognitive functioning was assessed by 10 neuropsychological tests from a battery. Neurocognitive test scores were converted to scale scores and t-scores using normative data from Chinese populations.ResultsMales were younger and less likely to be married, had an earlier age of illness onset and a longer duration of untreated psychosis (DUP), and scored higher on the PANSS negative, general and total scales than females. After controlling for potential confounders, females performed better than males in the verbal learning and memory domain (p=0.016). While most neurocognitive domains were correlated with PANSS negative scores for male patients with FES, for female patients with FES, negative associations were found between scores on the PANSS general subscales and neurocognitive domains. We also performed a case-control comparison with a group of patients with clinically stable schizophrenia (CSS) (n = 60) who were matched by age, sex and education years with patients with FES (n = 58). After controlling for potential confounders, no significant differences were found between patients with FES and patients with CSS in all neurocognitive domains. Female patients still performed better in the verbal learning and memory domain (t = 2.14, p = 0.034). No interaction effects of gender and disease were found.ConclusionsGender was an independent influence factor for the verbal learning and memory domain. Both female patients with first-episode schizophrenia and female patients with clinically stable schizophrenia performed better than male patients.     

The effect of schooling on reported age of onset of cognitive decline: A collaborative study

Higher education has been reported to be a protective factor against dementia. We suggest that the strength of a risk factor may be measured by the length of time by which it delays disease onset; therefore, we examined whether people with lower education develop cognitive decline at an earlier age than people with more schooling. The study population was based on patients referred to our Memory Clinics from 1994 to 2004. Analysis of covariance was used to evaluate the effect of schooling on the reported age of memory decline, in patients with mild cognitive impairment (MCI) and in patients diagnosed with Alzheimer’s disease (AD). The mean reported age of onset of cognitive decline was unexpectedly lower in patients with higher education than in patients with fewer schooling years, with a relatively small effect size (beta = −0.6), and the effect was more marked in the MCI group. Every year of schooling advanced the reported age of onset by 6 months among patients with MCI (t = −6.18, p < .001) and by 3 months among patients with AD (t = −2.4, p = 0.017). Education may affect the reported age of onset of cognitive decline, but its magnitude is small. It is possible that increased awareness in more educated people leads them to consult earlier; this could explain the paradoxical finding of earlier reported age of onset of cognitive decline in patients with higher education.     

Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder

ObjectiveTo determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder.MethodsThe clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria.Results172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows – RBD, 62 ± 14 (range, 20–93), cognitive impairment (n = 147); 69 ± 10 (range, 22–90), parkinsonism (n = 151); 68 ± 9 (range, 20–92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23–81). Death age was 75 ± 9 years (range, 24–96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1–61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson’s disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer’s disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features.ConclusionsIn this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.     

Performance on an Alzheimer-selective odor identification test in patients with Parkinson's disease and its relationship with cerebral dopamine transporter activity

BackgroundPrevious studies have shown selective deficits of odor identification in both Parkinson's disease (PD) and Alzheimer's disease (AD). Brief, selective AD smell screening tests have been developed to identify subjects at risk of AD. The disease specificity of such screening tests has not been formally evaluated.ObjectiveTo evaluate the performance of an Alzheimer-selective odor identification test in patients with PD and its relationship with cerebral dopamine transporter (DAT) activity.MethodsPD patients (n = 44; Hoehn and Yahr stages I–III; 13f/31 m; mean age 59.3 ± 10.1) and 44 controls matched for gender and age completed the University of Pennsylvania Smell Identification Test (UPSIT). All patients had PD duration > 1 year and none had evidence of dementia. Using the UPSIT, we calculated performance on the 10 odors previously reported to be selective for AD risk (UPSIT-AD10). A subset of 29 PD patients also underwent brain DAT [¹¹C]β-CFT (2-β-carbomethoxy-3β-(4-fluorophenyl) tropane) PET imaging. DAT binding was assessed in the hippocampus, amygdala, ventral and dorsal striatum.ResultsUPSIT-AD10 scores were significantly lower in the patient (5.8 ± 2.1) compared to the control group (8.6 ± 2.4) (t = 5.8, P < 0.0001). However, UPSIT-AD10 performance in the PD patients did not correlate with striatal or mesolimbic DAT activity.ConclusionsHyposmia in PD and AD overlap and supposed Alzheimer-selective smell screening tests may not be specific for AD. However, the supposed AD-selective hyposmia scores in PD did not correlate with cerebral DAT binding and may reflect a non-dopaminergic olfactory mechanism.     

Community based study of sleep bruxism during early childhood

ObjectivesThe aims for this study were to determine the prevalence of sleep-bruxism among young children, explore child behavior problems that may be associated with sleep-bruxism, and identify relations among sleep-bruxism, health problems, and neurocognitive performance.MethodsThe current study was a retrospective analysis of parent report surveys, and behavioral and neurocognitive assessments. Parents of 1953 preschool and 2888 first grade children indicated their child’s frequency of bruxism during sleep. A subsample of preschool children (n = 249) had additional behavioral, as well as neurocognitive assessments. Among the subsample, parents also reported on their child’s health, and completed the Child Behavioral Checklist; children were administered the Differential Ability Scales, and Pre-Reading Abilities subtests of the Developmental Neuropsychological Assessment.Results36.8% of preschoolers and 49.6% of first graders were reported to brux ⩾1 time per week. Among the preschool subsample, bruxing was independently associated with increased internalizing behaviors (β = .17). Bruxism was also associated with increased health problems (β = .19), and increased health problems were associated with decreased neurocognitive performance (β = .22).ConclusionsThe prevalence of sleep-bruxism was high. A dynamic and potentially clinically relevant relation exists among sleep-bruxism, internalizing behaviors, health, and neurocognition. Pediatric sleep-bruxism may serve as a sentinel marker for possible adverse health conditions, and signal a need for early intervention. These results support the need for an interdisciplinary approach to pediatric sleep medicine, dentistry, and psychology.     

Association between altered physical activity and neurocognitive function among people with schizophrenia: A minimum 6-months' follow-up study

BackgroundThe long-term benefits of physical activity on neurocognitive function among patients with schizophrenia, specifically among inpatients, remain unclear. This preliminary study, with a minimum of 6-months' follow-up, examined alterations in physical activity and neurocognitive function in both inpatients and outpatients with schizophrenia.MethodsSymptoms and neurocognitive function were assessed at 2 intervals using the Positive and Negative Symptom Scale and Cognitrax, respectively. After each testing period, participants wore an accelerometer for 1 week to measure their levels and duration of physical activity. After the 6-months' follow-up (average duration, 235.9 ± 36.2 days), participants were divided into 2 groups based on either increased or decreased activity, as compared with baseline: increased-activity and decreased-activity groups.ResultsOf the 29 initially enrolled participants, 25 (mean age, 56.8 ± 11.8 years) completed the follow-up. Reaction times in the increased-activity group in daily activity (n = 10) improved as compared with the decreased-activity group (n = 15). Moreover, cognitive flexibility and executive function improved in the increased-activity group in steps (n = 7) compared with the decreased-activity group (n = 18). Finally, there was no association between the duration of moderate or vigorous exercise and neurocognitive function.ConclusionsTogether, our results suggest that increased daily activity and walking, but not high intensity activity, are associated with improved neurocognitive function in patients with schizophrenia.     

Correlations between cognitive performances and psychotic or schizotypal dimensions

ObjectiveTo test if specific correlations exist between cognitive measures and psychotic dimensions in schizophrenic subjects and if similar correlations, between cognition and schizotypal dimensions, are present in non-psychotic subjects.MethodsWe administered the same battery of cognitive tests (Source Monitoring, Verbal Fluency [VF] and Stroop tests) to schizophrenic subjects (N = 54), their first-degree relatives (N = 37) and controls (N = 41). Scores of negative, positive and disorganisation dimensions were derived from the Signs and Symptoms of Psychotic Illness scale in schizophrenic subjects, and from the Schizotypal Personality Questionnaire in relatives and controls.ResultsIn schizophrenic subjects, as hypothesised, the negative dimension correlated with performance on VF and disorganisation with performance in the Stroop test. The positive dimension did not correlate with any cognitive measure.With only one exception, the significant correlations observed in non-psychotic subjects did not match correlations seen in schizophrenic subjects. In non-psychotic subjects greater disorganisation was associated with more clustered words in VF suggesting that excessive automatic spreading of activation in semantic networks could underlie this dimension.ConclusionAs a whole, data lent partial support to our hypothesis of specific cognitive–clinical correlations in schizophrenic subjects but did not support the existence of similar correlations in non-psychotic subjects.     

Syndrome de Susac : étude de cinq cas

IntroductionSusac syndrome is a rare microangiopathy, responsible for small cerebral, retinal and cochlear infarcts. The classic clinical triad includes multiple neurologic signs (from headaches to coma), retinal branch occlusions and sensorineural hearing loss.MethodsWe report a series of five patients with Susac syndrome followed in our department from 1997 to 2007.ResultsThere were four women and one man (mean age at onset: 35.2 years). Clinical symptoms at onset were neurological (n = 1), ophthalmological (n = 1), auditory (n = 1) and clinical triad (n = 2). Neurologic symptoms included encephalopathy (n = 2), headache (n = 5), transient ischemic attacks (n = 1). Brain MRI showed T2 lesions in the white and grey matter, corpus callosum and gadolinium-enhanced punctiform lesions. Cerebrospinal fluid contained an elevated protein level in three cases. Immunologic treatments (steroids [n = 4], cylophosphamid [n = 3], intravenous immunoglobulins [n = 5]) associated with aspirin and/or oral anticoagulants, despite early relapses (n = 2), led to dramatic clinical improvement (n = 5).ConclusionDue to its polymorphism the SS is difficult to diagnose when the clinical triad is lacking. In the absence of clinical trial and consensus treatment is empiric and based on supposed pathogenesis.     

Relationships between ophthalmic artery flow direction and cognitive performance in patients with unilateral carotid artery stenosis

BackgroundCerebral hypoperfusion is responsible for cognitive impairment in patients with severe carotid artery stenosis (CAS). The manifestation of reversed ophthalmic artery flow (ROAF) is not uncommon in patients with CAS, suggesting a state of intensified cerebral hypoperfusion. This study aimed to examine whether the presence of ROAF can exacerbate cognitive impairment in patients with severe unilateral CAS.MethodsOne-hundred-and-two patients with CAS and 37 age-matched volunteers participated in this case–control study. Depending on the side of CAS and occurrences of ROAF, the patients were allocated to four groups: left CAS groups with ROAF (n = 28) or without ROAF (n = 22), and right CAS groups with ROAF (n = 26) or without ROAF (n = 26). All subjects underwent a battery of neuropsychological tests.ResultsAll patients performed worse than the control group on most tests. No significant differences were observed between patient groups (ps > 0.05), except for inferior performance on psychomotor speed and visuospatial tests in the right ROAF group (ps < 0.03). Hierarchical regression analyses indicated strong contributions of estimated premorbid intelligence to performance on most tests (ps < 0.05). The severity of left and right CAS was distinctively associated with different functions. To a lesser extent, the severity of infarcts was also associated with impairment of psychomotor speed and some executive functions (ps < 0.05). The contributions of ROAF to performance on most tests were negligible.ConclusionPatients with unilateral CAS may present with specific cognitive impairment relevant to the ipsilateral hemispheric functions. However, the manifestation of ROAF does not necessarily imply more extensive or severe cognitive impairment.     

Neurophysiological evidence of cognitive inhibition anomalies in persons with major depressive disorder

ObjectiveThe neural correlates of inhibitory deficits for emotional semantic material in persons with major depressive disorder (MDD) were investigated.MethodsIndividuals (n = 15) with a diagnosis of MDD or MDD in partial remission, and healthy controls (n = 14) underwent recording of event-related brain potentials (ERPs) while performing a computerized emotional Stroop task.ResultsThere were no group performance differences on the emotional Stroop task. However, the analysis of ERP waveforms revealed a larger negative wave peaking at about 170 ms over the left than the right hemisphere only in controls; a negative displacement (N450) at parietal sites for positive and negative words only for persons with MDD; in both groups, processing negative and positive words was associated with a positive displacement that peaked at about 450 ms and was larger over the left lateral frontal region; and, the N450 modulation correlated with negative automatic thinking and depressive symptoms.ConclusionsThe electrophysiological data reveal early changes in neural activity associated with word processing as well as valence-related changes in the N450 component at parietal sites in MDD.SignificanceThis valence-related increase in N450 amplitude at parietal sites may reflect an automatic capture of attention by words with emotional valence.     

CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism

BackgroundCholesterol 24S-hydroxylase (CYP46) catalyzes the conversion of cholesterol to 24S-hydroxycholesterol, the primary cerebral cholesterol elimination product. Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer's disease (AD) and results are contradictory.MethodsWe performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.ResultsTwo of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p = 0.016; rs4900442: p = 0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p = 0.006). Haplotypes including both SNPs were calculated and haplotype G–C was identified to influence the risk of AD (p = 0.005). AD patients and non-demented controls, who were carriers of the G–C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p = 0.001) and cholesterol (p < 0.001).ConclusionOur results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.     

Continuous positive airway pressure deepens sleep in patients with Alzheimer’s disease and obstructive sleep apnea

ObjectivePatients with Alzheimer’s disease (AD) and obstructive sleep apnea (OSA) experience disrupted sleep. This study examined the effect of continuous positive airway pressure (CPAP) on sleep parameters in AD patients with OSA.MethodsA randomized placebo-controlled trial of 3 weeks of therapeutic CPAP (tCPAP) vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. Polysomnography data from screening after one night and after 3 weeks of treatment were analyzed. Records were scored for percent of each sleep stage, total sleep time (TST), sleep efficiency (SE), sleep period (SP), time in bed (TIB), sleep onset (SO), wake time after sleep onset (WASO), and arousals. A randomized design comparing one night of pCPAP to tCPAP and a paired analysis combining 3 weeks of tCPAP were performed.ResultsFifty-two participants (mean age = 77.8 years, SD = 7.3) with AD and OSA were included. After one treatment night, the tCPAP group had significantly less % Stage 1 (p = 0.04) and more % Stage 2 sleep (p = 0.02) when compared to the pCPAP group. In the paired analysis, 3 weeks of tCPAP resulted in significant decreases in WASO (p = 0.005), % Stage 1 (p = 0.001), arousals (p = 0.005), and an increase in % Stage 3 (p = 0.006).ConclusionIn mild to moderate AD patients with OSA, the use of tCPAP resulted in deeper sleep after just one night, with improvements maintained for 3 weeks.     

Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series

ObjectiveTo provide a 16-year update from the authors’ 1996 report documenting a 38% conversion from idiopathic rapid eye movement sleep behavior disorder (iRBD) to a parkinsonian disorder at a mean interval of nearly 13 years after the onset of iRBD in a series of 29 males ⩾50 years old.MethodsThe methods of evaluation, diagnosis and follow-up were previously described in the 1996 report. All patients had video-polysomnography (vPSG) confirmed RBD.Results80.8% (21/26) of patients who were initially diagnosed with iRBD eventually developed parkinsonism/dementia (three of the original 29 patients were lost to follow-up). The distribution of diagnoses was as follows: n = 13, Parkinson’s disease (PD); n = 3, dementia with Lewy bodies (DLB); n = 1, dementia (unspecified; profound); n = 2, multiple system atrophy (MSA); n = 2, clinically diagnosed Alzheimer’s Disease (AD) with autopsy-confirmed combined AD plus Lewy body disease pathology. Among the 21 iRBD “converters,” the mean age (±SD) of iRBD onset was 57.7 ± 7.7 years; mean age (±SD) of parkinsonism/dementia onset was 71.9 ± 6.6 years; and mean interval (±SD) from iRBD onset to parkinsonism/dementia onset was 14.2 ± 6.2 years (range: 5–29 years).ConclusionThe vast majority of men ⩾50 years old initially diagnosed with iRBD in this study eventually developed a parkinsonian disorder/dementia, often after a prolonged interval from onset of iRBD, with the mean interval being 14 years while the range extended to 29 years. Also, the specificity of iRBD converting to parkinsonism/dementia is striking. These findings carry important clinical and research implications in the convergent fields of sleep medicine, neurology, and neuroscience, and identify an optimal clinical group for conducting prospective research studies utilizing putative neuroprotective agents to delay the emergence of, or halt the progression to, parkinsonism and/or cognitive impairment as manifestations of either PD, DLB or MSA.     

Neurocognitive disturbances associated with acute infectious mononucleosis,Ross River fever and Q fever: A preliminary investigation of inflammatory and genetic correlates

Disturbances in neurocognitive performance are a core feature of the acute sickness response to infection; however the underlying mechanisms remain unclear. The current study used a computerised battery to assess neurocognitive functioning in subjects enrolled in the Dubbo Infection Outcomes Study (n = 107) – a prospective cohort of subjects followed from documented acute infection with Epstein Barr virus, Ross River virus, or Coxiella burnetii until recovery. Subjects were assessed when ill, and a subset again after complete recovery. Associations between sickness-related cognitive disturbances and single nucleotide polymorphisms (SNPs) in cytokine (interleukin [IL]-6, IL-10, tumor necrosis factor-α and interferon-γ) and neurobehavioral genes (serotonin transporter and catechol-O-methyltransferase) were explored.During acute infection, subjects exhibited slower matching-to-sample responses (p = 0.03), poorer working memory capacity (p = 0.014), mental planning (p = 0.045), and dual attention task performance (p = 0.02), and required longer to complete discordant Stroop trials (p = 0.01) compared to recovery. Objective impairments correlated significantly with self-reported symptoms (p < 0.05) as well as levels of the inflammation marker, C-reactive protein (p = 0.001). Linear regression analysis identified an association between neurocognitive disturbance during acute illness and functional polymorphisms in inflammatory cytokine genes. Specifically, the high cytokine producing G allele of the IL-6-174G/C SNP was associated with poorer neurocognitive performance when subjects were ill (p = 0.027).These findings confirm that acute infection impacts on neurocognitive performance, manifesting as slowed responses and impaired performance on complex tasks requiring higher-order functioning which has important real-world implications. The data provide the first preliminary evidence for a role of a genetic predisposition to more intense inflammatory responses in objective neurocognitive disturbances during acute infections. These associations require replication in a larger sample size.