Abstract:
:This study modeled predementia Alzheimer's disease clinical trials. Longitudinal data from cognitively normal (CN) and mild cognitive impairment (MCI) participants in the Alzheimer's Disease Neuroimaging Initiative were used to calculate sample size requirements for trials using outcome measures, including the Clinical Dementia Rating scale sum of boxes, Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-cognitive subscale with and without delayed recall, and the Rey Auditory Verbal Learning Task. We examined the impact on sample sizes of enrichment for genetic and biomarker criteria, including cerebrospinal fluid protein and neuroimaging analyses. We observed little cognitive decline in the CN population at 36 months, regardless of the enrichment strategy. Nonetheless, in CN subjects, using Rey Auditory Verbal Learning Task total as an outcome at 36 months required the fewest subjects across enrichment strategies, with apolipoprotein E genotype ε4 carrier status requiring the fewest (n = 499 per arm to demonstrate a 25% reduction in disease progression). In MCI, enrichment reduced the required sample sizes for trials, relative to estimates based on all subjects. For MCI, the Clinical Dementia Rating scale sum of boxes consistently required the smallest sample sizes. We conclude that predementia clinical trial conduct in Alzheimer's disease is enhanced by the use of biomarker inclusion criteria.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Grill JD,Di L,Lu PH,Lee C,Ringman J,Apostolova LG,Chow N,Kohannim O,Cummings JL,Thompson PM,Elashoff D,Alzheimer's Disease Neuroimaging Initiative.doi
10.1016/j.neurobiolaging.2012.03.006subject
Has Abstractpub_date
2013-01-01 00:00:00pages
62-72issue
1eissn
0197-4580issn
1558-1497pii
S0197-4580(12)00198-4journal_volume
34pub_type
杂志文章abstract::Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.11.026
更新日期:2016-03-01 00:00:00
abstract::Aggregates of hyperphosphorylated tau protein are a pathological hallmark of Alzheimer's disease (AD). The origin of AD is multifactorial, and many metabolic disorders originating from overconsumption of fat, cholesterol, and sugar are associated with higher risk of AD later in life. However, the effects of fat, chole...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.07.016
更新日期:2016-11-01 00:00:00
abstract::Several RNA sequences were tested for age-related changes in prevalence levels in the mouse cerebral cortex, hippocampus, and cerebellum. In all three regions, there were increased levels of RNA for glial fibrillary acidic protein, an astrocyte-specific protein, by RNA gel-blot analysis and by a solution hybridization...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(91)90056-p
更新日期:1991-03-01 00:00:00
abstract::In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can i...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.10.014
更新日期:2016-02-01 00:00:00
abstract::We previously found a selective loss of the brain specific APP-695 transcript in Alzheimer's disease (AD) cortex, which results in a 2.5-fold increase in the APP-751/APP-695 transcript ratio in AD (9). Here we report a similar increase in APP-751/APP-695 mRNA ratio in AD hippocampus. However, the cerebellum had a 6-fo...
journal_title:Neurobiology of aging
pub_type: 更正并重新发布的文章,杂志文章
doi:10.1016/0197-4580(89)90017-1
更新日期:1989-11-01 00:00:00
abstract::Despite recognition that Alzheimer's disease (AD) is a polygenic and heterogeneous dementing neurodegenerative disorder, there is continued merit in defining the AD phenotype by the presence of progressive cognitive impairments and the pathological brain lesions (senile plaques, neurofibrillary tangles) as originally ...
journal_title:Neurobiology of aging
pub_type: 杂志文章,评审
doi:10.1016/s0197-4580(97)00075-4
更新日期:1997-07-01 00:00:00
abstract::The total number of immunocytochemically identified vasopressin (AVP) cells was determined morphometrically in the paraventricular (PVN) and dorsolateral part of the supraoptic nucleus (dl-SON) of the human hypothalamus in 30 subjects ranging in age from 15 to 97 years, including 10 Alzheimer's disease (AD) patients. ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(95)80003-a
更新日期:1995-01-01 00:00:00
abstract::An experiment was performed to test the ability of Centrophenoxine to reduce the amount of lipofuscin (age pigment) in the retinal pigment epithelium (RPE) of aged rhesus monkeys. Centrophenoxine is reputed to have this action in neurons of lower mammals. Quantitative electron microscopic analysis was performed on sec...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(86)90148-x
更新日期:1986-03-01 00:00:00
abstract::The hippocampal perforant pathway originates in the entorhinal cortex (ERC) and terminates in the outer molecular layer of the dentate gyrus (DG). To compare the effects of normal aging and Alzheimer's disease (AD) on the elements of the perforant pathway, we compared relative perikaryal numbers (determined by countin...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(92)90115-e
更新日期:1992-05-01 00:00:00
abstract::Although senile plaques represent a consistent neuropathological feature in Alzheimer's brains, it is not known what role plaques play in the etiology of the disease. Both growth-promoting and growth-inhibiting influences have been postulated. One of the major components in plaques, beta-amyloid, has been shown to aff...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(93)90002-s
更新日期:1993-05-01 00:00:00
abstract::The brains of 14 rhesus monkeys (Macaca mulatta) between 4 and 35 years old were examined to determine the effects of aging on the thickness, neuronal frequency, fine structure, surface area, and volume of striate cortex. The effects of aging were ascertained by comparing the striate cortex in the six monkeys between ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(96)00208-4
更新日期:1997-01-01 00:00:00
abstract::The basal forebrain (BF) cholinergic system is selectively vulnerable in human brain diseases, while the cholinergic groups in the upper pons of the brainstem (BS) resist neurodegeneration. Cholinergic neurons (200 per region per animal) were laser-microdissected from five young (8 months) and five aged (24 months) F3...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2007.04.024
更新日期:2008-12-01 00:00:00
abstract::A common analogy to aging is that of a boulder being worn down to rubble by the unremitting onslaught of time. In contrast, Swaab's "use it or lose it" concept is important because it emphasizes some positive consequences of experience. For example, early exposure to complex experience may offer some protection from "...
journal_title:Neurobiology of aging
pub_type: 评论,杂志文章
doi:10.1016/0197-4580(91)90009-9
更新日期:1991-07-01 00:00:00
abstract::Parkinson's disease (PD) and Alzheimer's dementia (AD) are often associated with an autonomic neuropathy. The extent of autonomic involvement, however is poorly defined and unpredictable. In order to assess the autonomic cardiovascular regulation baroreflex sensitivity (BRS) was determined non-invasively in 23 patient...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(01)00210-x
更新日期:2001-05-01 00:00:00
abstract::Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition betwee...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.05.007
更新日期:2014-11-01 00:00:00
abstract::Abnormal neuronal excitability and impaired synaptic plasticity might occur before the degeneration and death of neurons in Alzheimer's disease (AD). To elucidate potential biophysical alterations underlying aberrant neuronal network activity in AD, we performed whole-cell patch clamp analyses of L-type (nifedipine-se...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.07.007
更新日期:2014-01-01 00:00:00
abstract::In order to investigate inflammation and apoptosis in Creutzfeldt-Jakob disease (CJD) patients, we analyzed astrocytes, microglia and apoptotic neurons in brain and IL-1beta in cerebrospinal fluid (CSF). Our results showed increased numbers of astrocytes in CJD and increased numbers of microglia and apoptotic neurons ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(01)00236-6
更新日期:2002-01-01 00:00:00
abstract::The present study was designed to examine the effects of the aging process on the response of motoneurons to axotomy. Accordingly, in aged cats using intracellular recording techniques, the electrophysiological properties of axotomized lumbar spinal cord motoneurons were compared with those of control (nonaxotomized) ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(92)90035-v
更新日期:1992-03-01 00:00:00
abstract::An association between semicarbazide-sensitive amine oxidase (SSAO) and cerebral amyloid angiopathy (CAA) related to Alzheimer's disease (AD) has been largely postulated. Increased SSAO activity and expression have been detected in cerebrovascular tissue and plasma of AD patients, colocalizing with cerebrovascular amy...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2014.09.030
更新日期:2015-02-01 00:00:00
abstract::Support has recently been voiced for the genetic hypothesis of Alzheimer's disease; frequently at the expense of considerations of environmental factors. In the adult, genetic diseases rarely exist without modification by environment forces. Atherosclerosis leading to myocardial infarction may provide a useful model t...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(89)90093-6
更新日期:1989-09-01 00:00:00
abstract::Estrogens have been implicated as possible therapeutic agents for improving cognition in postmenopausal women and have been linked to neurodegenerative disorders such as Alzheimer's disease. However, the utility of Premarin (Wyeth Pharmaceuticals, Markham, ON, Canada), a conjugated equine estrogen and the most commonl...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.07.009
更新日期:2013-03-01 00:00:00
abstract::The objective of this study was to determine whether physiological fluctuations in white matter (PFWM) on resting-state functional magnetic resonance images could be used as an index of neurodegeneration and Alzheimer's disease (AD). Using resting-state functional magnetic resonance image data from participants in the...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.09.010
更新日期:2016-01-01 00:00:00
abstract::Firing characteristics of "place" cells in dorsal CA1 of hippocampus were recorded from 5 young (10-14 months) and 5 old (25-29 months) Fischer-344 rats. Animals were trained to obtain food reward on a radial 8-arm maze. Entry to the arms was controlled by the experimenter so that all 8-arm were visited in random sequ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(83)90034-9
更新日期:1983-07-01 00:00:00
abstract::Eyeblink conditioning is a relatively simple form of associative learning that shows neurobiological and behavioral parallels across several species, including humans. Aged subjects acquire eyeblink conditioning more slowly than young ones. In addition, eyeblink conditioning effectively discriminates patients with Alz...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2006.03.006
更新日期:2007-05-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving motor neurons. Because a growing number of genes have been identified as the genetic etiology of ALS, simultaneous screening of mutations in multiple genes is likely to be more efficient than gene-by-gene testing. In this ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.09.012
更新日期:2016-01-01 00:00:00
abstract::Omegaconotoxin binding was studied in young (3 months) and old (24 months) male Sprague-Dawley rats. In both groups omegaconotoxin binding displayed high affinity, was specific and saturable. The age-related changes are mainly a decrease in the Bmax in striatum and cortex (-29% and -31%, respectively). Binding paramet...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(90)90010-w
更新日期:1990-07-01 00:00:00
abstract::In these experiments, potential cognitive deficits in aged rats were studied using an odor-reward association task. Aged Fischer 344 rats first performed to an odor-reward association task. After five daily sessions of 60 trials, the aged rats were globally impaired in comparison to the control rats. However, consider...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(95)02030-6
更新日期:1996-01-01 00:00:00
abstract::Age related alterations in mnemonic ability and in the functional status of muscarinic receptors were evaluated and compared to biochemical measures of pre and post-synaptic cholinergic functioning. Retention of a single trial passive avoidance task was considerably disturbed as a function of aging. The functional sta...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(80)90019-6
更新日期:1980-07-01 00:00:00
abstract::In the axon terminals of the locus coeruleus (LC) neurons, a high level of axonal branching was occurred in the middle-aged brain, and the increased branching was maintained in the aged brain. In the present study, we hypothesized that neurotrophic support is necessary for the morphological age-related changes seen in...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/S0197-4580(03)00093-9
更新日期:2004-03-01 00:00:00
abstract::A loss of hippocampal neurons and synapses had been considered a hallmark of normal aging and, furthermore, to be a substrate of age-related learning and memory deficits. Recent stereological studies in humans have shown that only a relatively minor neuron loss occurs with aging and that this loss is restricted to spe...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(98)00098-0
更新日期:1998-11-01 00:00:00