Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort.

OBJECTIVES: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). METHODS: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. RESULTS: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. CONCLUSIONS: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline.

ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Using the Frontal Assessment Battery to identify executive function impairments in amyotrophic lateral sclerosis: A preliminary experience.

Up to 50% of persons with amyotrophic lateral sclerosis (ALS) develop cognitive impairments, particularly of executive function (EF). The Frontal Assessment Battery (FAB) provides a method for rapid assessment of EF. We investigated the FAB as an assessment of cognitive impairment among 16 subjects with ALS, and evaluated their performance on the FAB and the Mini-Mental State Examination (MMSE). Raw FAB and MMSE scores were Z-transformed using published age- and education-based norms. FAB Z-scores were significantly lower than MMSE Z-scores (p<0.03). Eight subjects (50%) were impaired (Z < or = -2) on the FAB while no subjects were impaired on the MMSE. MMSE and FAB scores did not vary as function of disease duration, laterality of onset, or Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Further study of the suitability of the FAB as a domain-specific screening measure of executive dysfunction for ALS is warranted.

Reduplicative paramnesia in Morvan's syndrome.

BACKGROUND: Morvan's syndrome is characterized by peripheral nervous system hyperexcitibility (myokymia and neuromyotonia), hyperhydrosis, sleep disorder, limb paresthesias, and encephalopathy. Voltage gated potassium channel antibodies (VGKC abs) are frequently present. Reduplicative paramnesia (RP) has not been reported with this disorder. OBJECTIVE: To describe a patient with Morvan's syndrome presenting with RP. DESIGN: Single case study. PATIENT: A 64-year-old man with several years of myokymia and myoclonus with escalating parasomnia and confusion developed the delusion that a replica of his house and its contents existed 40 mi away. RESULTS: Serum VGKC ab titer was elevated. Neuropsychological testing disclosed executive function and memory deficits. Electromyography demonstrated diffuse myokymia. Treatment with intravenous immunoglobulin and prednisone produced improvement of RP and myoclonus, but not myokymia. CONCLUSION: RP may occur in patients with VGKC ab-associated Morvan's syndrome. Both RP and nervous system hyperexcitability may respond to immunotherapy including intravenous immunoglobulin and corticosteroids.

The genetics of very early onset Alzheimer disease.

OBJECTIVE: This study was undertaken to clarify the genetics of very early onset Alzheimer disease (VEOAD), defined as AD beginning before age 35. BACKGROUND: Early onset AD (EOAD) is defined by onset of symptoms before age 65, and affected individuals may harbor a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein. VEOAD is exceedingly rare, and PSEN1 mutations have been implicated. We encountered a man with phenotypic frontotemporal dementia beginning at age 32 and a strong family history of an autosomal dominant dementia who was found at autopsy to have AD. METHODS: Histologic and genetic analyses of the patient's brain were undertaken, and a review of all published VEOAD cases was performed. RESULTS: Histologic findings were diagnostic of advanced stage AD. Genetic evaluation of brain tissue identified an intronic PSEN1 polymorphism; no known pathogenic mutation was found. Literature review (1934 to 2007) disclosed 101 cases of VEOAD; the youngest age of dementia onset was 24 years. In all cases in which definitive genetic analysis was available, either a PSEN1 mutation or linkage to chromosome 14 was found. CONCLUSIONS: VEOAD can present with atypical clinical features, including findings suggestive of frontotemporal dementia. All reported cases of VEOAD with conclusive genetic analysis seem to be associated with PSEN1 mutations. Genetic testing in adults younger than 35 with dementia can identify the genetic defect and assist in diagnosis and family counseling.