Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare inborn disorder of L-lysine, L-hydroxylysine, and L-tryptophan metabolism complicated by striatal damage during acute encephalopathic crises. Three decades after its description, the natural history and how to treat this disorder are still incompletely understood. To study which variables influenced the outcome, we conducted an international cross-sectional study in 35 metabolic centers. Our main outcome measures were onset and neurologic sequelae of acute encephalopathic crises. A total of 279 patients (160 male, 119 female) were included who were diagnosed clinically after clinical presentation (n ϭ 218) or presymptomatically by neonatal screening (n ϭ 23), high-risk screening (n ϭ 24), or macrocephaly (n ϭ 14). Most symptomatic patients (n ϭ 185) had encephalopathic crises, characteristically resulting in bilateral striatal damage and dystonia, secondary complications, and reduced life expectancy. First crises usually occurred during infancy (95% by age 2 y); the oldest age at which a repeat crisis was reported was 70 mo. In a few patients, neurologic disease developed without a reported crisis. Differences in the diagnostic criteria and therapeutic protocols for patients with GCDH deficiency resulted in a huge variability in the outcome worldwide. Recursive partitioning demonstrated that timely diagnosis in neurologically asymptomatic patients followed by treatment with L-carnitine and a lysine-restricted diet was the best predictor of good outcome, whereas treatment efficacy was low in patients diagnosed after the onset of neurologic disease. Notably, the biochemical phenotype did not predict the clinical phenotype. Our study proves GCDH deficiency to be a treatable disorder and a good candidate for neonatal screening.

Objective: To determine whether dementia with Lewy bodies (DLB) progresses more rapidly than Alzheimer disease (AD). Methods: We compared 315 participants (63 with DLB and 252 with AD) enrolled in a prospective longitudinal study of memory and aging with annual clinical and cognitive assessments and followed until death. The main outcome measure was dementia progression to institutionalization and death. Neuropathologic examinations were performed on all participants in this study. Subject classification (DLB vs AD) was based on neuropathology. Results: Patients with DLB had an increased risk of mortality vs patients with AD (hazard ratio [HR] 1.88, 95% CI: 1.4 to 2.5). The median survival time for DLB was 78.0 years and for AD was 84.6 years ( 2 ϭ 19.9, p Ͻ 0.001) with significant modification effects due to gender (HR 1.51, 95% CI: 1.0 to 2.3) and the presence of at least 1 APOE ε4 allele (HR 1.50, 95% CI: 1.0 to 2.2). Survival after dementia onset was also different between DLB and AD (7.3 vs 8.5 years; 2 ϭ 5.4, p Ͻ 0.02). DLB cases had similar risks of institutionalization and survival in long-term care facilities to AD cases. Self-reports of depression and the presence of extrapyramidal signs were important covariates. The rate of cognitive decline as measured by psychometric performance and clinical staging methods did not differ between DLB and AD. Conclusions: Dementia with Lewy bodies (DLB) increases the risk of mortality compared with Alzheimer disease (AD), but the two groups did not differ in rate of cognitive decline. The greater risk for noncognitive disease progression for DLB compared with AD suggests clinically meaningful differences for the two disorders. NEUROLOGY 2006;67:1935-1941 Dementia with Lewy bodies (DLB), a common cause of dementia after Alzheimer disease (AD), accounts for up to 30% of cases in autopsy series. 1-3 Consensus clinical criteria for diagnosis of DLB 4 are marked by poor sensitivity, particularly for those individuals with concurrent AD pathology. 5-7 Although a small percentage of DLB patients have only Lewy body (LB) pathology at autopsy, 6 the majority of patients with DLB have mixed AD and LB pathology. 4,6-9 This distinction has clinical relevance as patients with mixed pathology are often difficult to distinguish clinically from those with AD. 4,6,7 We therefore chose to examine outcomes in neuropathologically defined, rather than clinically defined, groups.Clinical progression of AD is well characterized, with mean duration of 8 to 12 years. 6,10 The clinical progression of DLB, however, has not fully been elucidated. There are conflicting reports in the literature regarding disease progression. Several earlier studies indicate that the time from diagnosis of DLB to death is 6 years or less, 11-13 with evidence of more rapid cognitive progression as compared with AD. 6,7,13 There are also reports demonstrating no difference in survival for DLB vs AD. 2, 14 We investigated whether DLB progresses more rapidly than AD to relevant clinical endpoints such as nursing home...

In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.

Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis.

Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re‐evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well‐informed decisions in the context of MMA and PA patient care.

In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.

African Americans experience a greater risk of Alzheimer's disease (AD), but are underrepresented in AD research. Our study examined barriers and facilitators of AD research participation among African Americans. Investigators conducted 11 focus groups with African American participants (n=70) who discussed barriers and facilitators to AD research participation including lumbar puncture (LP) studies. The moderator and co-moderator independently reviewed transcripts, identified themes, and coded transcripts for analysis. Participants were predominately female (73%) with a mean age of 52y (range 21-86y). Concerns and attitudes were consistent across education, socioeconomic status, and gender. Mistrust was a fundamental reason for nonparticipation. Additional barriers included insufficient information dissemination in the African American community, inconvenience, and reputation of the researcher and research institution. Barriers to participation in AD biomarker studies were fear of the unknown and adverse effects. Altruism and relevance of research projects to the individual, family members, or the African American community facilitate participation. Increased participation results from relationships with the community that extend beyond immediate research interests, dissemination of research findings, and emphasis on relevance of proposed studies. Pervasive barriers impede African American participation in AD research but can be overcome through a sustained presence in the community.