Richard J Caselli

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..To date, this has impacted study design in some research trials but not clinical practice...

..To assess the possible contribution of TOMM40 to Alzheimer's disease onset, we compared the effects of TOMM40 and APOE genotype on preclinical longitudinal memory decline...

..To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype...

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..To provide a current survey of the clinical and pathologic features, known genetic and suggested pathogenic contributions, diagnosis, and treatment of Alzheimer's disease (AD) and related forms of dementia...

..These results correlate with imaging and neuropathological studies that show AD-like changes at this age and collectively support the existence of a presymptomatic stage of AD...

..In addition to pharmacotherapy, important lifestyle issues confronting the clinician include driving cessation, securing any weapons maintained at home, assisted living, and caregiver burnout...

..To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE...

..Nondemented APOE e4 carriers over age 60 have a higher burden of total parenchymal and vascular amyloid neuropathology than NC, but no difference in neuritic plaque and NFT pathology...

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..To correlate memory measures with a trait measure of chronic daytime somnolence in cognitively normal individuals with different gene doses of the apolipoprotein E (APOE) e4 allele, a common Alzheimer's disease susceptibility gene...

..These changes could represent presymptomatic disease in some, despite their youth...

..To test the hypothesis that healthy adults reporting dream-enactment behavior (DEB+) have reduced cerebral metabolic rate for glucose (CMRgl) in regions preferentially affected in patients with dementia with Lewy bodies (DLB)...

..The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown...

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..pole/neocortex, and posterior cingulate by age 65 years in APOE ε4 carriers prior to the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), but is it impairing frontally mediated neuropsychological performance?..

..To describe an organizational schema of human creativity...

..Chronic anxiety adversely affects cognitive skills in all groups, and is associated with significantly greater decline in problem solving skills in cognitively normal APOE e4 HMZ...

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..We also provide this high-quality, low post-mortem interval (PMI), cell-specific, and region-specific NDAD/AD reference data set to the community as a public resource...

..034; OR=1.29) and in a combined analysis of 1026 additional living and expired subjects (P=0.039; OR=1.26). Our findings suggest that KIBRA is associated with both individual variation in normal episodic memory and predisposition to AD...

..We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD...

..The authors previously found accelerated whole brain atrophy rates in patients with probable Alzheimer's disease by computing changes in brain volume from sequential magnetic resonance images (MRIs)...

..This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk...

..We provide this carefully phenotyped, laser capture microdissected intraindividual brain region expression data set to the community as a public resource...

..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...

..The results support the role of cholesterol-related genes in the predisposition to AD and support the value of neuroimaging in the presymptomatic assessment of putative modifiers of AD risk...

..Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia...

..It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk...

..To examine cognitive effects of pharmacologically induced somnolence in cognitively normal carriers and noncarriers of the apolipoprotein E (APOE)-epsilon4 allele, a common Alzheimer's disease susceptibility gene...

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..These preliminary findings provide additional evidence that higher BP, likely a reflection of arterial stiffness, during late midlife may be associated with increased risk of presymptomatic AD...

..To provide preliminary validation data on a self- or informant-report multidimensional questionnaire of symptoms associated with neurodegenerative disorders...

..Therefore, cholinesterase inhibitors might improve cognitive function in PDD. On the other hand, enhancing cholinergic function could plausibly worsen features of parkinsonism...

..7 × 10(-4)). Our findings support the possibility of using the MMPLS to analyze complementary datasets from the same person in the presymptomatic detection and tracking of AD...

..This suggests that longitudinal study of new learning is a sensitive measure for detecting early cognitive changes in at-risk individuals that precede the symptomatic onset of mild cognitive impairment and AD...

..Most of these studies have been cross-sectional, and often look at patients already with dementia. This leaves uncertainty with regard to the temporal relationship of circadian disruption and cognitive decline...

..To determine whether apolipoprotein E (apo E) genotype influences intellectual achievement in cognitively normal individuals...

..We encourage investigators involved in longitudinal studies to consider causes for missing data, especially when secondary to participant refusal...

..This functional biomarker may prove useful in early detection and tracking of AD and indicates that mitochondrial mechanisms may contribute to the predisposition to AD before any evidence of amyloid or tau pathology...

..Evidence that the use of memantine in a patient already on cholinesterase inhibitor therapy can provide a clinically significant benefit is limited...

..Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology...

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..The association of executive-functioning difficulties and anxiety appears more likely to occur in persons who are most at risk for subsequent cognitive decline...

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..Mild cognitive impairment, topography and semiology of dementia syndromes, reversible forms of dementia, dementia therapy, driving, genetic testing of patients and family members, and caregiver risk are reviewed...

..To describe a case of childhood-onset progressive multiple sclerosis with dementia and evidence of extensive cortical demyelination from brain biopsy specimen...

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

..This procedure is important because NAIM can be treated successfully if it is distinguished from the nontreatable dementias that mimic it...

..We sought to determine the most commonly used drugs used to treat behavioral variant FTD (bvFTD) in specialized dementia clinics...

..To determine whether a diagnosis of idiopathic rapid-eye-movement sleep behavior disorder (RBD) is associated with a future risk of development of neurodegenerative diseases...

..Progress in decreasing the variance of MUNEs will facilitate their use in detecting small motor unit number changes in neurodegenerative disease...

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..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...

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..This research might lead to the identification of novel therapeutic targets for the treatment and/or prevention of Alzheimer's disease...

..These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders...

..Paraneoplastic syndromes typically require tumor removal and often prove fatal. CNS vasculitides may respond to steroid therapy, but often require a second agent such as cyclophosphamide...

..More effective preventive strategies could notably impact morbidity, mortality, and health care costs...

..Although the myoclonus occurred without dementia in these cases, its relationship to the subsequent development of cognitive impairment remains to be defined...

..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...

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..More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex...

..Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders...

..Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia...

..No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers...

..Prompt treatment with corticosteroids is essential in order to minimize the frequency of permanent sequelae such as visual loss and stroke...

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..Results suggest that the medial temporal response over repeated presentation is related to clinical status. Probes of incremental encoding processes over trials may be useful markers of medial temporal lobe integrity...

..This review will focus on the possible role of vascular risk factors in modulating the risk of age-related cognitive decline, and the progression of predementia syndrome such as MCI to dementia...

..To clarify the sources of discrepant findings in the literature, this review summarizes existing epidemiological studies of the defined clinical predementia syndromes and their progression to dementia...

..We evaluated the impact of depressive symptoms on the rate of incident mild cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the interaction between depressive symptoms and vascular risk factors for incident MCI...

..Scaled Subprofile Model network analysis may aid in the detection and tracking of brain aging and in the evaluation of putative antiaging therapies...

..Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory...

..Apolipoprotein E (ApoE) genotype and aerobic fitness are each associated with cognitive performance in older adults. However, their potentially interactive effects on cognitive performance have not been examined...

..We estimated the prevalence and incidence rates of depressive symptoms and the role of vascular risk factors and sociodemographic variables on the occurrence of depressive symptoms in mild cognitive impairment (MCI)...

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..Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease...