D Knopman

..However, knowledge of cognitive and functional status in MCI still leaves much uncertainty regarding the ability to predict worsening...

..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...

..Several new agents targeted directly at amyloid beta peptide production are currently in clinical trials, but no large studies have been reported over the past year...

..Strokes, vascular risk factors, and apolipoprotein E (APOE) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited...

..The incidence rates (new cases per 100,000 person-years) were 2.2 for ages 40 to 49, 3.3 for ages 50 to 59, and 8.9 for ages 60 to 69. For comparison, the corresponding rates for Alzheimer disease were 0.0, 3.3, and 88.9...

..Because there is only limited longitudinal imaging data currently available, we measured the rate of change over 1 year of whole brain volume (WBV) and ventricular volume (VV) in patients with FTLD...

..Defining the nature of the contribution of stroke to cognitive impairment remains challenging...

..There are several candidate outcome measures -- including the FTLD-CDR and the cognitive composites -- that could be used in clinical trials across the spectrum of FTLD...

..Although advances in imaging have increased our recognition of cerebrovascular disease in the elderly, vascular dementia is still inadequately recognized in clinical practice...

..Because of similarities between brain and kidney microvascular disease, there may be a relationship between measures of renal microvascular disease and brain structural changes in middle aged or elderly individuals...

..Because cardiovascular (CV) risk factors have been associated with declines in cognitive functions and late life dementia, CV risk factors should also be associated with brain atrophy...

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

..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...

..The overlap between cerebrovascular disease and Alzheimer disease produces a disorder that might be amenable to therapeutic approaches based on either mechanism...

..Information on the incidence of nondegenerative and nonvascular dementia is limited...

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

..The telephone assessment of cognitive functions may reduce the cost and burden of epidemiological studies...

..To investigate the relationship between features and definitions of vascular dementia (VaD) and survival...

..To examine the contribution of cerebrovascular disease to dementia...

..Other areas of investigation with disappointing results, such as estrogen replacement therapy, anti-inflammatory approaches, and several other therapeutic agents, are also reviewed...

..In addition, a multicenter trial is described in which some aspects of diagnosis and longitudinal measurement in the frontotemporal lobar degenerations are being specifically explored...

..The CDRstd does not specifically address language dysfunction or alteration in personality and social behaviors which are prominent in behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA)...

..The role of vascular risk factors in midlife should be the focus of public health efforts to reduce the burden of late-life cognitive impairment...

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..The main threat to the accuracy of the estimates is the difficulty in diagnosing the clinical syndromes that comprise the FTLD group of disorders...

..Other areas of investigation with disappointing results such as estrogen replacement therapy and antiinflammatory approaches are discussed. Several other potential therapeutic agents are also reviewed...

..The validity of the clinical diagnosis of vascular dementia (VaD) remains suboptimal...

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..The experience of the past 2 decades has set the stage for discovering the next generation of anti-AD drugs and introducing those therapies at milder stages of the disease...

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..In this article, the advantages and disadvantages of passive case-finding were discussed, and the following conclusion was drawn: the purpose of the study being conducted should determine the case-finding approach that is to be used...

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

..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...

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

..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)...

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..To determine whether certain aspects of fluctuations reliably distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and normal aging...

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

..To better understand the role of SVD in cognitive function, we investigated the relationship between retinal microvascular abnormalities and longitudinal changes in cognitive function in a community-based study...

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

..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...

..Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life...

..No data exist on whether the syndrome of amnestic mild cognitive impairment occurs in the oldest old, or if the relationships for functional status and neuropsychometric performance based on clinical diagnosis hold true in this age group...

..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...

..To assess the feasibility of using MRI measurements as a surrogate endpoint for disease progression in a therapeutic trial for AD...

..To determine whether adding REM sleep behavior disorder (RBD) to the dementia with Lewy bodies (DLB) diagnostic criteria improves classification accuracy of autopsy-confirmed DLB...

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

..To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN)...

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

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

..At least some of the frontotemporal dementias, which in this article encompass the progressive aphasias, have mutations in the tau gene that account for some of the phenotypic variations...

..The current study provides a basis for pursuing larger controlled trials with betaine in AD. The homocysteine to S-adenosylmethionine pathway is of interest in AD therapeutics...

..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)...

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

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

..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...

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

..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)...

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

..To determine if synucleinopathy pathology is related to REM sleep behavior disorder (RBD) plus dementia or parkinsonism...

..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...

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

..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)...

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

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

..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...

..The global impression of a clinician is an Food and Drug Administration--mandated primary outcome measure for clinical trials in dementia. Reliability and validity of these measures are not well established...

..VaD is an entity that provides many challenges to the clinician, neuroradiologist and neuropathologist in part because evidence-based studies often lack clear definitions of the disease...

..To update the 1994 practice parameter for the diagnosis of dementia in the elderly...

..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...

..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...

..These finding extend prior research suggesting a cognitive profile that can aid in the clinical diagnosis of DLB. Early attention and visual perceptual disturbance suggests DLB, while early impairment in memory and naming suggests AD...

..97; hazard ratio 7-point DSST score increment = 0.86, 95% confidence interval: 0.80, 0.93). Cognitive function measured in middle age appears to have prognostic importance for life expectancy similar to that reported in elderly adults...

..These findings suggest that the insR352 PSEN1 is not pathogenic, and the IVS1+1G-->A mutation in PGRN causes FTDP associated with FTLD-U pathology and represents a new class of neurodegenerative disease--the 'hypoprogranulinopathies'...

..It is not known, however, whether patients who meet the criteria for PCA and have hallucinations are different from those who meet the criteria and do not have hallucinations...

..These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD...

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..As new treatments become available for Alzheimer disease, the most common of the dementias, accurate diagnosis allows the appropriate patients to receive treatment...

..22 (95% CI=0.38, 3.87). These findings do not demonstrate a significant association between T levels and dementia. However, they suggest a need for further investigation of these potential associations...

..68 (95% CI=0.35-1.32) among never-smokers (P for interaction=0.01). Our findings do not confirm a significant association between ET and AD overall; however, the possible interaction with smoking deserves further study...

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

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

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

..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...

..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 ability to detect the clinical signs of dementia and motor neuron disease in pathologically confirmed FTLD-MND has not been assessed...

..Choline/creatine ratio declined in stable MCI, compared to converter MCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in MCI patients who did not to progress to AD...

..It remains unknown whether depression and apolipoprotein E genotype are risk factors for incident mild cognitive impairment (MCI)...

..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...

..There is inadequate information regarding the neuropsychiatric aspect of Mild Cognitive Impairment (MCI)...

..000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI...

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