R C Petersen

..4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects)...

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..Future research directions to help clarify some of the remaining uncertainties are proposed...

..The neuropathologic substrate of amnestic mild cognitive impairment (aMCI) is not known...

..The recently completed clinical trials as well as neuropsychological and nutritional interventions are discussed. Finally, the clinical utility of MCI, and directions for future research are proposed...

..While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made...

..We investigated the prevalence of mild cognitive impairment (MCI) in Olmsted County, MN, using in-person evaluations and published criteria...

..The neuropathology of MCI is intermediate between the neuropathologic changes of aging and fully developed Alzheimer's disease. The breadth of research in MCI is expanding and will be reviewed...

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..It is proposed that the clinical criteria for mild cognitive impairment be enriched with imaging and other biomarkers to improve the specificity of the outcome, and these criteria might suffice for pre-dementia clinical trials...

..Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally...

..This review summarizes the progress that has been made while also recognizing the challenges that remain...

..Ultimately, it is likely that the use of a combination of neuroimaging and chemical biomarkers will be involved in predicting the development of dementia and Alzheimer's disease (AD)...

..Mild cognitive impairment is an important topic for research in aging and dementia and has also become the subject of several multicenter treatment trials...

..To investigate the combined ability of hippocampal volumes, 1H magnetic resonance spectroscopy (MRS) metabolites, and cerebrovascular disease to predict the risk of progression to dementia in mild cognitive impairment (MCI)...

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..Comparisons were based on intergroup discrimination, correlation with concurrent cognitive/functional changes, relationships to APOE genotype, and sample sizes for clinical trials...

..To assess the correlations of both MRI and CSF biomarkers with clinical diagnosis and with cognitive performance in cognitively normal (CN) subjects and patients with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD)...

..We included comparisons to subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN)...

..To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA)...

..We aimed to determine whether right temporal FTD is a homogeneous clinical, imaging, and pathologic/genetic entity...

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..002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy...

..Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity...

..To determine the relationship between β-amyloid (Aβ) load as measured by [(11)C]-Pittsburgh compound B (PiB) PET and cognitive function in cognitively normal older adults...

..We estimated the incidence of amnestic MCI (aMCI) and nonamnestic MCI (naMCI) in men and women separately...

..69%, AD 3. 5%. CONCLUSION: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD...

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..To determine the proton magnetic resonance spectroscopy ((1)H MRS) changes in carriers of microtubule-associated protein (MAPT) mutations in a case-control study...

..To examine the relationship between early clinical features, pathologies, and biochemistry of the frontotemporal lobar degenerations (FTLDs), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)...

..To use multiple serial MRI to assess rates and trajectories of brain and hippocampal atrophy in subjects with frontotemporal dementia (FTD) with progranulin (GRN) or microtubule-associated protein tau (MAPT) gene mutations...

..We have observed severe caudate atrophy at autopsy in FTLD-FUS, and hence, we aimed to determine whether caudate atrophy on MRI is a feature that can distinguish FTLD-FUS from FTLD-TDP and FTLD-TAU...

..To determine the patterns of diffusivity associated with cognitive domain functions in older adults without dementia...

..We suggest that PSP with or without coexisting AD and AGD be included in the differential diagnosis of patients presenting with FTD...

..To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene...

..To investigate age-related default mode network (DMN) connectivity in a large cognitively normal elderly cohort and in patients with Alzheimer disease (AD) compared with age-, gender-, and education-matched controls...

..The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly...

..To compare logistic and bilogistic models to describe the pattern of cognitive decline in the preclinical phase of Alzheimer disease (AD)...

..CONCLUSIONS: Amnestic mild cognitive impairment is associated with increased mortality, which is greater in multiple-domain aMCI than in single-domain aMCI. Mortality in aMCI subtypes may vary by APOE-epsilon4 allele status...

..To compare the patterns of gray matter loss in subjects with amnestic mild cognitive impairment (aMCI) who progress to Alzheimer disease (AD) within a fixed clinical follow-up time vs those who remain stable...

..Decreased glucose metabolism in the temporal and parietal lobes on FDG-PET is recognized as an early imaging marker for the AD pathology. Our objective was to investigate the effects of age on FDG-PET findings in aMCI...

..To determine the anatomic correlate of prosopagnosia in subjects with semantic dementia...

..The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS...

..MI/Cr levels are elevated in dementias that are pathologically characterized by gliosis, such as AD and FTLD. Cho/Cr levels are elevated in dementias that are characterized by a profound cholinergic deficit, such as AD and DLB...

..CONCLUSION: In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD...

..To examine the clinical, genetic, and neuropathologic features of posterior cortical atrophy (PCA)...

..Limitations and unique features of MOANS normative data are also discussed...

..0 (i.e., chance) to 34.9. The clinical usefulness of absolute scores and difference scores in data interpretation is supported. Neither profile variability measures nor measures of change over time were diagnostically useful...

..To compare patterns of gray matter loss in subjects with mutations in the progranulin (PGRN) gene to subjects with mutations in the microtubule-associated protein tau (MAPT) gene...

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..To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD)...

..Although several studies reported weight loss preceding the onset of dementia, other studies suggested that obesity in midlife or even later in life may be a risk factor for dementia...

..We aimed to determine whether patterns of gray matter atrophy from antemortem MRI correlate with Braak staging of NFT pathology...

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..These cases demonstrate that atypical PSP can present as AOS and PNFA without the classic features of PSP...

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..Limitations and unique features of the MOANS normative data are also discussed...

..Elevation in hippocampal ADC may reflect early ultrastructural changes in the progression of Alzheimer disease...

..99 SD, and moderate AD (CDR 2) -2.22 SD. Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process...

..Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD...

..Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals...

..The neuropsychological-hippocampal volume correlations indicate that hippocampal volume measurements do represent a measure of the structural substrate of functional impairment in AD...

..In addition, fMRI is sufficiently sensitive to detect changes in the prodromal, MCI, phase of the disease...

..The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD)...

..To study coronary artery bypass grafting (CABG) as a risk factor for dementia and Alzheimer disease (AD) using a case-control design...

..An analysis of patient outcomes in these cases reveals that FTLD-MND has significantly shorter survival than FTLD-U, suggesting that FTLD-MND is a more aggressive disease process...

..Limitations and unique features of MOANS normative data are also discussed...

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..Collectively these results suggest that although BNT impairments become more common as AD progresses, they are neither necessary for the diagnosis of AD nor particularly useful in identifying early AD...

..To determine the frequency and possible cognitive effect of histological Alzheimer's disease (AD) in autopsied older nondemented individuals...

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..Greater CA1 and subicular atrophy can be demonstrated early and is predictive of future conversion to AD, whereas CA2-3 involvement becomes more evident as the disease progresses...

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..These results also suggest that 3D patterns of grey matter atrophy may help to predict the time to the first diagnosis of AD in subjects with aMCI...

..We propose the term neurofilament inclusion body disease for this entity...

..To characterize a kindred with a familial neurodegenerative disorder associated with a mutation in progranulin (PGRN), with emphasis on the unique clinical features in this kindred...

..Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families...

..On the other hand, there is no histopathologic feature or combination of features that is pathognomonic. Neuronal intranuclear inclusions are virtually always present, but they can be detected in PGRN(-) cases...

..Selection of imaging measures used for clinical assessment or monitoring efficiency of therapeutic intervention should be tailored to the clinical stage of the disease...

..The dissipation of the APOE effect in old-old individuals at lower risk of AD suggests that visuospatial attention impairments seen as early as midlife in APOE-e4 carriers may be a preclinical marker of AD...

..To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease...

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..Among 1H-MRS measurements, the NAA/MI ratio maybe the most efficient predictor of memory and cognitive function in patients with MCI and AD...

..The trajectories of brain and ventricular changes were similar in AD and FTLD-U suggesting that it is independent of pathology, although subjects with FTLD-U show a more rapidly progressive decline...

..AD patients with clinical CBS have similar characteristics to CBD patients. Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD...

..To investigate the impact white matter hyperintensities (WMH) detected on magnetic resonance imaging have on motor dysfunction and cognitive impairment in elderly subjects without dementia...

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..We propose that plasma GRN levels could be used as a reliable and inexpensive tool to identify all GRN mutation carriers in early-onset dementia populations and asymptomatic at-risk individuals...

..AGD is a common pathologic finding in subjects who have been diagnosed with amnestic MCI...

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..Damage to this network of structures in DLB may affect a number of different neurotransmitter systems which in turn may contribute to a number of the core clinical features of DLB...

..To estimate the incidence of dementia after the first atrial fibrillation (AF), and its impact on survival in a community-based cohort...

..Underlying CBD should be considered in the differential diagnosis of patients with findings reflecting posterior cerebral dysfunction...

..7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17...

..This population-based cohort will be a valuable resource for additional research on epidemiology, clinical characteristics, neuropsychological features, neuroimaging measures, and neuropathological substrate of prodromal dementia. ..