Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal

Apostolova, Liana G.; Mosconi, Lisa; Thompson, Paul M.; Green, Amity E.; Hwang, Kristy; Ramírez, Anthony; Mistur, Rachel L.; Tsui, Wai; Leon, Mony J. de

doi:10.1016/j.neurobiolaging.2008.08.008

Cited by 269 publications

(249 citation statements)

References 47 publications

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“…Additionally, the present results are in line with a longitudinal MRI study demonstrating significant atrophy in medial temporal, inferolateral temporal, and parietal lobes and posterior cingulate in families with early-onset AD circa five years before the diagnosis of AD [36], as well as studies with sporadic AD patients which demonstrated atrophy of medial temporal lobe structures four to ten years before the AD diagnosis [37][38][39][40][41].…”

Section: Discussionsupporting

confidence: 90%

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Hirni

Kivisaari

Krumm

et al. 2016

JAD

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Abstract. Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g., semantic object memory impairments) may predate or accompany ERC (i.e., episodic memory) dysfunction in the preclinical course of typical AD. We developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness) using common neuropsychological tests in 31 healthy individuals and 58 early AD patients. These formulae estimated the longitudinal courses of mPRC and ERC functioning in independent groups of 28 optimally healthy individuals who developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC-NC estimated mPRC and ERC functioning at the earliest observation,

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Section: Discussionsupporting

confidence: 90%

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Hirni

Kivisaari

Krumm

et al. 2016

JAD

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“…Several of these studies have determined that, compared to the subgroup remaining CN over follow-up, the subgroup of CN-decliners had smaller baseline brain structures, including hippocampal formation and temporoparietal cortical regions. [22][23][24][25][26] A few other investigations have reported MTL and whole brain atrophy in the presymptomatic stage of genetically determined early-onset familial AD, again supporting the concept that atrophy as measured on MRI, while often subtle, may be present for a number of years prior to the development of AD-related symptoms. [27][28][29] Yet at least one similarly designed study found that ventricular volume was predictive of decline, but hippocampal, entorhinal, or whole brain volume were not.…”

Section: Ad-like Csf Is More Common In Mri-defined Highmentioning

confidence: 68%

MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults

Dickerson¹,

Wolk²

2012

Neurology

186

138

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Objective: New preclinical Alzheimer disease (AD) diagnostic criteria have been developed using biomarkers in cognitively normal (CN) adults. We implemented these criteria using an MRI biomarker previously associated with AD dementia, testing the hypothesis that individuals at high risk for preclinical AD would be at elevated risk for cognitive decline.Methods: The Alzheimer's Disease Neuroimaging Initiative database was interrogated for CN individuals. MRI data were processed using a published set of a priori regions of interest to derive a single measure known as the AD signature (ADsig). Each individual was classified as ADsig-low (Ն1 SD below the mean: high risk for preclinical AD), ADsig-average (within 1 SD of mean), or ADsig-high (Ն1 SD above mean). A 3-year cognitive decline outcome was defined a priori using change in Clinical Dementia Rating sum of boxes and selected neuropsychological measures.Results: Individuals at high risk for preclinical AD were more likely to experience cognitive decline, which developed in 21% compared with 7% of ADsig-average and 0% of ADsig-high groups (p ϭ 0.03). Logistic regression demonstrated that every 1 SD of cortical thinning was associated with a nearly tripled risk of cognitive decline (p ϭ 0.02). Of those for whom baseline CSF data were available, 60% of the high risk for preclinical AD group had CSF characteristics consistent with AD while 36% of the ADsig-average and 19% of the ADsig-high groups had such CSF characteristics (p ϭ 0.1). Although it has been known for years that Alzheimer disease (AD) neuropathology may be present in individuals who were cognitively normal (CN) prior to death, 1-6 this population is receiving increasing recent attention. In 2010 -2011 expert groups published diagnostic criteria for "preclinical" AD that hinge upon biological markers, calling for longitudinal study of individuals who meet criteria. 7,8 Although the core of preclinical AD criteria is molecular biomarker evidence of amyloid-␤ deposition, abnormalities of brain structure or function topographically consistent with AD-related neurodegeneration are also considered supportive preclinical AD biomarkers. Conclusions:Here we performed a hypothesis-driven analysis to answer this question: if CN older adults harbor an MRI biomarker suggestive of early AD neurodegeneration, are they more likely to develop cognitive decline than CN individuals lacking this marker?

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“…38 Our observations were also consistent with an MRI study, which found that CA2 atrophy was more strongly associated with mild cognitive impairment and progression to dementia than CA1 atrophy in AD. 39 Neuronal atrophy appears to be a potential mechanism relating CA2 atrophy to cognitive impairment in the absence of extensive CA2 neuron loss.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Neuronal Atrophy and Cognitive Function in Delayed Poststroke and Aging-Related Dementias

Gemmell

Bosomworth

Allan

et al. 2012

Stroke

131

115

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Background and Purpose-We have previously shown delayed poststroke dementia in elderly (Ն75 years old) stroke survivors is associated with medial temporal lobe atrophy; however, the basis of the structural and functional changes is unknown. Methods-Using 3-dimensional stereological methods, we quantified hippocampal pyramidal neuronal volumes and densities in a total of 95 postmortem samples from demented and nondemented poststroke survivors within our prospective Cognitive Function after Stroke study and subjects pathologically diagnosed with vascular dementia, Alzheimer disease, and mixed Alzheimer disease and vascular dementia syndrome. Results-Hippocampal CA1 but not CA2 subfield neuron density was affected in poststroke, Alzheimer disease, vascular dementia, and mixed dementia groups relative to control subjects (PϽ0.05). Neuronal volume was reduced in the poststroke dementia relative to poststroke nondemented group in both CA1 and CA2, although there were no apparent differences in neuronal density. Poststroke nondemented neuronal volumes were similar to control subjects but greater than in all dementias (PϽ0.05). Neuronal volumes positively correlated with global cognitive function and memory function in both CA1 and CA2 in poststroke subjects (PϽ0.01). Degrees of neuronal atrophy and loss were similar in the poststroke dementia and vascular dementia groups. However, in the entorhinal cortex layer V, neuronal volumes were only impaired in the mixed and Alzheimer disease groups (PϽ0.05). Conclusions-Our results suggest hippocampal neuronal atrophy is an important substrate for dementia in both cerebrovascular and neurodegenerative disease. (Stroke. 2012;43:808-814.)

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Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal

Cited by 269 publications

References 47 publications

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer’s Dementia

MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults

Hippocampal Neuronal Atrophy and Cognitive Function in Delayed Poststroke and Aging-Related Dementias

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