Multiple pathologies are common in Alzheimer patients in clinical trials.

OBJECTIVE: To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology. METHODS: We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology. RESULTS: Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02). CONCLUSION: While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.

Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial.

OBJECTIVE: To assess the efficacy of lamotrigine, a novel antiepileptic drug that inhibits glutamate release, to retard disease progression in Huntington disease (HD). BACKGROUND: Excitatory amino acids may cause selective neuronal death in HD, and lamotrigine may inhibit glutamate release in vivo. METHODS: A double-blinded, placebo-controlled study was conducted of 64 patients with motor signs of less than 5 years' duration who were randomly assigned to either placebo or lamotrigine and assessed at 0 (baseline), 12, 24, and 30 months. The primary response variable was total functional capacity (TFC) score. Secondary response variables included the quantified neurological examination and a set of cognitive and motor tests. Repeated fluorodeoxyglucose measurements of regional cerebral metabolism using PET also were included. RESULTS: Fifty-five patients (28 on lamotrigine, 27 on placebo) completed the study. Neither the primary response variable nor any of the secondary response variables differed significantly between the treatment groups. Both the lamotrigine and the placebo group deteriorated significantly on the TFC, in the lamotrigine group by 1.89 and the placebo group by 2.11 points. No effect of CAG size on the rate of deterioration could be detected. CONCLUSIONS: There was no clear evidence that lamotrigine retarded the progression of early Huntington disease over a period of 30 months. However, more patients on lamotrigine reported symptomatic improvement (53.6 versus 14.8%; p = 0.006), and a trend toward decreased chorea was evident in the treated group (p = 0.08). The study also identified various indices of disease progression, including motor tests and PET studies, that were sensitive to deterioration over time.

Pathological association and dissociation of functional systems in multiple sclerosis and Huntington's disease.

This study examined pathological associations and dissociations of functional cognitive systems in patients with multiple sclerosis and Huntington's disease. Using the subtests of the WAIS-R, two motor tests, and the word fluency test, the interest correlations showed distinct patterns. In comparison to normals, the two clinical groups exhibited a greater degree of association among the tests. Subsequently, word fluency performance was predicted from these tests. For the normals, the overall predictive power was quite low (7%). For the MS group, the predictive power rose to 28%. For the HD group, the predictive power was 50%. These results suggest that pathological association of functional systems may be a marker of brain dysfunction and that the affected systems may be delineated by these methods.