Prospective memory in idiopathic REM sleep behavior disorder with or without mild cognitive impairment: A preliminary study.

OBJECTIVE: The ability to execute delayed intentions, known as prospective memory (PM), is crucial to everyday living. PM failures are reported in mild cognitive impairment (MCI) and Parkinson's disease, however, no study to date has investigated PM functioning in individuals at high risk of developing these conditions, precisely those diagnosed with idiopathic REM sleep behavior disorder (iRBD). We aimed to assess PM in iRBD according to patients' cognitive status and to determine the underlying nature of their difficulties. METHOD: Fifty-eight participants, including 20 healthy controls (HC) and 38 polysomnographic-confirmed iRBD patients with (iRBD-MCI = 13) or without (iRBD-nMCI = 25) MCI participated in this study. Following a neuropsychological assessment, PM was evaluated using a self-administered questionnaire (PRMQ), a simple clinical measure (envelope test), and a laboratory cue salience task. RESULTS: No significant group differences were noted on the PRMQ and envelope test. On the PM laboratory task, non-parametric analyses revealed better detection accuracy in HC than both iRBD groups for all high and low salient cues. While iRBD-nMCI and iRBD-MCI patients performed similarly on the high salient condition, the latter showed significant difficulty in detecting low salient cues. Multiple regression analyses revealed executive dysfunction as the best predictor to significantly account for differences in the low salient condition in iRBD. CONCLUSION: PM difficulties in iRBD are most important in patients with MCI (vs without MCI) and may be attributed to a gradual alteration in executive mechanisms. PM impairment could act as a promising indicator of early cognitive dysfunction in iRBD.

Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

OBJECTIVES: Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. DESIGN: Prospective cohort study. SETTING: Tertiary sleep disorders center. PARTICIPANTS: 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. MEASUREMENTS/RESULTS: Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). CONCLUSIONS: Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.

Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: a prospective study.

One of the most devastating nonmotor manifestations of PD is dementia. There are few established predictors of dementia in PD. In numerous cross-sectional studies, patients with rapid eye movement (REM) sleep behavior disorder (RBD) have increased cognitive impairment on neuropsychological testing, but no prospective studies have assessed whether RBD can predict Parkinson's dementia. PD patients who were free of dementia were enrolled in a prospective follow-up of a previously published cross-sectional study. All patients had a polysomnogram at baseline. Over a mean 4-year follow-up, the incidence of dementia was assessed in those with or without RBD at baseline using regression analysis, adjusting for age, sex, disease duration, and follow-up duration. Of 61 eligible patients, 45 (74%) were assessed and 42 were included in a full analysis. Twenty-seven patients had baseline RBD, and 15 did not. Four years after the initial evaluation, 48% with RBD developed dementia, compared to 0% of those without (P-adjusted = 0.014). All 13 patients who developed dementia had mild cognitive impairment on baseline examination. Baseline REM sleep atonia loss predicted development of dementia (% tonic REM = 73.2 ± 26.7 with dementia, 40.8 ± 34.5 without; P = 0.029). RBD at baseline also predicted the new development of hallucinations and cognitive fluctuations. In this prospective study, RBD was associated with increased risk of dementia. This indicates that RBD may be a marker of a relatively diffuse, complex subtype of PD.

Mild cognitive impairment in moderate to severe COPD: a preliminary study.

BACKGROUND: Cognitive impairment is a frequent feature of COPD. However, the proportion of patients with COPD with mild cognitive impairment (MCI) is still unknown, and no screening test has been validated to date for detecting MCI in this population. The goal of this study was to determine the frequency and subtypes of MCI in patients with COPD and to assess the validity of two cognitive screening tests, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), in detecting MCI in patients with COPD. METHODS: Forty-five patients with moderate to severe COPD and 50 healthy control subjects underwent a comprehensive neuropsychologic assessment using standard MCI criteria. Receiver operating characteristic curves were obtained to assess the validity of the MMSE and the MoCA to detect MCI in patients with COPD. RESULTS: MCI was found in 36% of patients with COPD compared with 12% of healthy subjects. Patients with COPD with MCI had mainly the nonamnestic MCI single domain subtype with predominant attention and executive dysfunctions. The optimal MoCA screening cutoff was 26 (≤ 25 indicates impairment, with 81% sensitivity, 72% specificity, and 76% correctly diagnosed). No MMSE cutoff had acceptable validity. CONCLUSIONS: In this preliminary study, a substantial proportion of patients with COPD were found to have MCI, a known risk factor for dementia. Longitudinal follow-up on these patients is needed to determine the risk of developing more severe cognitive and functional impairments. Moreover, the MoCA is superior to the MMSE in detecting MCI in patients with COPD.

Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder.

OBJECTIVE: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying "preclinical" neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of synuclein-mediated neurodegenerative disease--this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. METHODS: Patients with RBD without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. Olfaction and color vision were tested at baseline, then annually for 5 years. Test results were compared between patients who developed neurodegenerative disease and those who remained disease-free. RESULTS: Out of 64 patients, 62 (97%) participated in annual follow-up. During follow-up, 21 developed disease, and 41 remained disease-free. Out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. Compared to those remaining disease-free, patients destined to develop disease had worse baseline olfaction (University of Pennsylvania Smell Identification Test [UPSIT] = 58.3 ± 27.0% age/sex-adjusted normal vs 80.2 ± 26.3%; p = 0.003) and color vision (Farnsworth-Munsell 100-Hue color test [FM-100] errors 153.0 ± 82.2% normal vs 120.2 ± 26.5%; p = 0.022). Kaplan-Meier 5-year-disease-free survival in those with normal olfaction was 86.0%, vs 35.4% with impaired olfaction (p = 0.029). Disease-free survival with normal color vision was 70.3%, vs 26.0% with impaired vision (p = 0.009). Both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages. INTERPRETATION: Olfaction and color vision identify early-stage synuclein-mediated neurodegenerative diseases. In most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages.

The Montreal Cognitive Assessment: a screening tool for mild cognitive impairment in REM sleep behavior disorder.

Mild cognitive impairment (MCI) is a frequent feature in idiopathic REM sleep behavior disorder (RBD), a sleep disturbance that can be a preclinical stage of Parkinson's disease or Lewy body dementia. We evaluated the sensitivity and specificity of two brief screening tools, the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), in detecting MCI in idiopathic RBD. Thirty-eight idiopathic RBD patients underwent a comprehensive neuropsychological assessment, including the MoCA and the MMSE. Receiver operating characteristic curves were created for the MoCA and the MMSE to assess their ability to identify MCI in idiopathic RBD patients, with neuropsychological assessment as the gold standard. For the MoCA, a normality cutoff of 26 yielded the best balance between sensitivity (76%) and specificity (85%) with a correct classification of 79%. For the MMSE, the optimal normality cutoff was 30, with a sensitivity of 84% and a specificity of 54% and a correct classification of 74%. The MoCA is superior to the MMSE in detecting MCI in idiopathic RBD patients, showing good sensitivity and very good specificity.

A verbal planning impairment in adult ADHD indexed by script generation tasks.

OBJECTIVE: Though juvenile and adult ADHD cases are well known to have a nonverbal planning impairment, a verbal-planning impairment has been demonstrated only in juvenile ADHD. The purpose of this investigation is to determine whether a verbal planning impairment also characterizes adult ADHD. METHODS: A cohort of 30 adult ADHD clients of a university psychological clinic are compared to 30 age-, education-, gender-, and IQ-matched persons recruited from the general population who did not have ADHD. The dependent measure is a set of 6 paper/pencil 10-item script generation tasks. RESULTS: The findings reveal that the ADHD cohort was significantly impaired on the script task and the script task correlated significantly with severity of ADHD (CAARS index + WURS), whereas several neuropsychological measures of executive function (Stroop, COWA, Rey's Complex Figure, D2, CVLT, CPT-II) did not. Findings further showed that the script measure was weakly correlated with the other established neuropsychological measures of executive function (r < .46, shared variance of less than 21%). CONCLUSIONS: On the basis of the study findings, it is concluded that verbal planning measured with script generation tasks is distinctly impaired in clinically referred adult ADHD.

Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson's disease.

OBJECTIVE: To investigate the frequency and subtypes of mild cognitive impairment (MCI) in idiopathic rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease (PD) in association with RBD. METHODS: One hundred and twelve subjects without dementia or major depression including 32 idiopathic RBD patients, 22 PD patients with polysomnography-confirmed RBD, 18 PD patients without RBD, and 40 healthy control subjects, underwent a comprehensive neuropsychological evaluation. We compared the proportion of patients with MCI between groups using standard diagnostic criteria. RESULTS: MCI was found in 50% of idiopathic RBD patients and 73% of PD patients with RBD. In contrast, only 11% of PD patients without RBD and 8% of control subjects had MCI. The presence of MCI was significantly greater in idiopathic RBD patients and PD patients with RBD than in PD patients without RBD and control subjects. PD patients with RBD also performed worse than idiopathic RBD patients on neuropsychological tests assessing visuoconstructional and visuoperceptual abilities. INTERPRETATION: In both its association with PD and its idiopathic form, RBD is an important risk factor for MCI. Except for visuoconstructional and visuoperceptual problems, RBD may be an important determinant of cognitive impairment in PD. Ann Neurol 2009;66:39-47.