PubMed · 12876939
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Keiji Okimoto, Susumu Ijuin, Hiroaki Nakahara, Kiyoto Kasai, Akira Iwanami. 2003. [Other persistent delusional disorder].. https://pubmed.ncbi.nlm.nih.gov/12876939/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Alzheimer's disease (AD) is characterized by the presence of toxic protein aggregates or plaques composed of the amyloid β (Aβ) peptide. Various lengths of Aβ peptide are generated by proteolytic cleavages of the amyloid precursor protein (APP). Mutations in many familial AD-associated genes affect the production of the longer Aβ42 variant that preferentially accumulates in plaques. In the case of sporadic or late-onset AD, which accounts for greater than 95% of cases, several genes are implicated in increasing the risk, but whether they also cause the disease by altering amyloid levels is currently unknown. Through loss of function studies in a model cell line, here RNAi-mediated silencing of several late onset AD genes affected Aβ levels is shown. However, unlike the genes underlying familial AD, late onset AD-susceptibility genes do not specifically alter the Aβ42/40 ratios and suggest that these genes probably contribute to AD through distinct mechanisms.
BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS: Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS: We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.).
BACKGROUND: Several demographic and phenomenological variables have been identified as predictors of outcome in schizophrenia. Far fewer studies have examined the relationships between brain morphology assessed at illness onset and subsequent outcome, and their results have been contradictory. METHODS: The relationships between magnetic resonance imaging (MRI) regional brain volumes at illness onset and outcome five years later were studied in 123 schizophrenia patients using regression and correlation analysis. Outcome measures included psychosocial functioning, weeks per year receiving inpatient treatment, and persistence of severe psychotic, disorganized and negative symptoms. RESULTS: Temporal lobe tissue volume at onset was predictive of outcome. Smaller temporal lobe gray matter volume (both left and right) was associated with persistence of hallucinations during follow-up. There were no significant associations between hallucinations and temporal white matter, or between delusions and temporal white or gray matter volumes. None of the other volumetric brain measures were predictive of outcome. CONCLUSIONS: The association between initial temporal lobe gray matter volume and subsequent persistent hallucinations may help identify individuals who are at higher risk for poor outcome and help guide their treatment planning. However, regional brain volumes assessed near illness onset, in general, do not appear to be indicative of subsequent outcome in schizophrenia.