Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

This study was designed to evaluate whether subjects with amyloid beta (Aß) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aß pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aß+) or negative (Aß-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aß+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aß+ MCI subjects demonstrated greater worsening compared with Aß- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aß+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aß+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aß+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aß+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aß+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aß- subjects do.

Safety and tolerability of rivastigmine transdermal patch compared with rivastigmine capsules in patients switched from donepezil: data from three clinical trials.

OBJECTIVES: To compare the safety and tolerability of switching patients with mild-to-moderate Alzheimer's disease from donepezil to either rivastigmine capsule or transdermal patch. METHODS: Three studies investigated the switch from donepezil to rivastigmine; study US13 was a 26-week, single-arm, immediate-switch study; US18 was a 26-week, sequential cohort study (both studies evaluated rivastigmine capsules 3-12 mg/day); study US38 was a 25-week, randomised, parallel-group, open-label study which investigated switch (immediate or after 7 days' withdrawal) from donepezil to rivastigmine transdermal patch (4.6 mg/24 hr). Safety outcomes included adverse events (AEs), discontinuations caused by AEs and serious AEs (SAEs). RESULTS: Patient groups receiving rivastigmine patch (n = 261) or capsules (n = 331) had mean +/- SD ages of 77.3 +/- 8.0 and 78.1 +/- 7.8 years, dementia durations of 3.9 +/- 2.6 and 3.6 +/- 2.2 years and Mini-Mental State Examination scores of 18.3 +/- 4.00 and 17.9 +/- 4.4 respectively. Overall, 184 (70.5%) and 276 (83.4%) patients experienced at least one AE, and 23 (8.8%) and 55 (16.6%) patients experienced an SAE with the rivastigmine patch and capsules respectively. Of the patients who experienced an AE, 10 (3.8%) and 109 (32.9%) experienced nausea, and 11 (4.2%) and 80 (24.1%) experienced vomiting with the rivastigmine patch and capsules respectively. Discontinuations because of AEs occurred in 64 (19.3%) patients receiving capsules and 38 (14.6%) patients in the transdermal patch group. The most common reasons for discontinuation with the transdermal patch were application site reaction and disease progression, and nausea and vomiting with the capsules. CONCLUSIONS: The rivastigmine transdermal patch appears to have better tolerability than rivastigmine capsules, with fewer gastrointestinal AEs and discontinuations because of these AEs. Simple daily rotation of patch location will likely reduce the frequency of skin reactions. This post hoc analysis was carried out by Novartis Pharmaceuticals Corporation. Data for the analysis were collected from the US13 study (CENA713B US13), the US18 study (CENA713B US18) and the US38 study (CENA713D US38).

Postradiation motor neuron syndrome.

We report an unusual case of selective lower motor neuron syndrome (MNS) complicating whole neuraxis radiation therapy. Only three well-documented similar cases have been found in a thorough review of the literature. The syndrome has a stereotyped time course and is self-limited. We discuss here possible pathogenetic mechanisms and their relationship to motor neuron disease.

Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease.

OBJECTIVE: To examine the effects of tacrine hydrochloride in patients with Alzheimer disease (AD) and detectable baseline deficits in discrete cognitive and noncognitive parameters who are enrolled in a previously reported multicenter, double-blind, 30-week trial. DESIGN: An exploratory analysis using last observation carried forward. The study population included a placebo group (n = 181) and all patients randomized to treatment within 160 mg/d of tacrine hydrochloride (n = 234), regardless of highest dose achieved or duration of tacrine therapy. STUDY POPULATION: Male and female subjects, at least 50 years of age, with mild to moderate AD and detectable baseline deficits in discrete cognitive and noncognitive parameters. MAIN OUTCOME MEASURES: Change from baseline to last observation carried forward in discrete subscale scores of the Alzheimer's Disease Assessment Scale (ADAS): cognitive (memory, language, praxis) and noncognitive (mood, behavior). Improvement was defined as a decrease of at least 1 point from baseline; stabilization was defined as no change or a decrease from baseline. RESULTS: Compared with the placebo group, the percentage of patients receiving tacrine whose conditions improved or stabilized was significantly greater for 8 of 11 ADAS-cognitive items (word recall, word recognition, orientation, language production, comprehension, word finding, following commands, ideational praxis) and for the ADAS-noncognitive items: cooperation, delusions, and pacing. CONCLUSIONS: Tacrine stabilizes or improves specific behavioral deficits and symptoms in AD. The previous demonstration of tacrine's effect on global cognitive function has been extended by suggesting an association between tacrine therapy and improvements in individual cognitive and noncognitive items of the ADAS. Effects of tacrine in clinical practice might be more accurately and efficiently assessed by measuring individual ADAS cognitive and noncognitive items relevant to individual patient pretreatment clinical status.

Alexia without agraphia, hemianopia, or color-naming defect: a disconnection syndrome.

A patient with alexia without agraphia, hemianopia, or color-naming defect was found at operation to have a meningioma arising from the tentorium cerebelli that compressed the inferior aspect of the left temporal-occipital junction. It is presumed to have involved only the left ventral visual association cortex and its inferior outflow tracts to the angular gyrus. The input from the right occipital area also was disconnected from the visual language verbal association area by involvement of the ventral outflow of the splenium of the corpus callosum. Preservation of color naming and matching suggests that these functions are dependent on the integrity of more dorsal occipital association systems.

Sclerosing spinal pachymeningitis. A complication of intrathecal administration of Depo-Medrol for multiple sclerosis.

Reported complications of intrathecal steroid therapy include aseptic meningitis, infectious meningitis, and arachnoiditis. We report a case of sclerosing spinal pachymeningitis complicating the attempted intrathecal administration of Depo-Medrol for multiple sclerosis. The lesion is characterised by concentric laminar proliferation of neomembranes within the subdural space of the entire spinal cord and cauda equina, resulting from repeated episodes of injury and repair to the spinal dura mater by Depo-Medrol. There is clinical and laboratory evidence that Depo-Medrol produces meningeal irritation and that the vehicle is the necrotising fraction.

A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group.

OBJECTIVE: To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease. DESIGN: A 12-week, double-blind, placebo-controlled, parallel-group study. SETTING: Outpatients at 23 centers. PATIENTS: Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions. INTERVENTIONS: In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC). RESULTS: Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P = .014), clinician-rated CGIC (P = .014), and caregiver-rated CGIC (P = .006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P = .015), clinician-rated CGIC (P = .016), and caregiver-rated CGIC (P = .028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment-related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%). CONCLUSIONS: These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations.