Presenilin-1–associated abnormalities in regional cerebral perfusion

Johnson, Keith A.; Lopera, Francisco; Jones, Ken; Becker, Alex; Sperling, Reisa A.; Hilson, Julie A.; Londoño, Jessica; Siegert, I.; Arcos, Mauricio; Moreno, Sonia; Madrigal, Lucía; Ossa, Jorge; Pineda, Nicolás; Ardila, Alfredo; Roselli, Martina; Albert, Marilyn; Kosik, Kenneth S.; Ríos, Ángela

doi:10.1212/wnl.56.11.1545

Cited by 69 publications

(51 citation statements)

References 38 publications

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“…Using perfusion SPECT, we found regional functional abnormalities in IQ-MI subjects at baseline in a temporoparietal distribution that is similar to the distribution reported in MCI subjects who subsequently converted to AD (Chetelat et al, 2003;Johnson et al, 1998). Similar findings have also been reported in mild AD (Johnson et al, 2001). More recently, evidence of early AD pathology in these regions was confirmed among MCI patients who came to autopsy (Bradley et al, 2002;Markesbery et al, 2006;Petersen et al, 2006).…”

Section: Dm Rentz Et Alsupporting

confidence: 84%

“…These methods may have limited specificity with respect to non-AD causes of dementia (Rutschmann & Matchar, 2002); however, image abnormalities have been reported in the prodromal phase of AD, reflecting early changes in brain physiology that have now been shown to portend further decline (Johnson et al, 1998(Johnson et al, , 2007Mungas et al, 2002). For example, temporoparietal hypoperfusion has been reported in nondemented subjects with cognitive impairment who later converted to AD (Chetelat et al, 2003;Johnson & Albert, 2000;Nestor et al, 2003), and in asymptomatic carriers of the PS1 gene mutation with autosomal dominant inheritance, which causes early onset AD (Johnson et al, 2001). In this study, our objective was to investigate whether individuals identified as IQ-MI showed evidence of functional imaging abnormalities at baseline and a higher likelihood of subsequent declines in cognition and daily living skills.…”

Section: Introductionmentioning

confidence: 99%

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Intelligence quotient–adjusted memory impairment is associated with abnormal single photon emission computed tomography perfusion

Rentz

Huh

Sardinha

et al. 2007

J. Inter. Neuropsych. Soc.

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Cognitive reserve among highly intelligent older individuals makes detection of early Alzheimer's disease (AD) difficult. We tested the hypothesis that mild memory impairment determined by IQ-adjusted norms is associated with single photon emission computed tomography (SPECT) perfusion abnormality at baseline and predictive of future decline. Twenty-three subjects with a Clinical Dementia Rating (CDR) score of 0, were reclassified after scores were adjusted for IQ into two groups, 10 as having mild memory impairments for ability (IQ-MI) and 13 as memory-normal (IQ-MN). Subjects underwent cognitive and functional assessments at baseline and annual follow-up for 3 years. Perfusion SPECT was acquired at baseline. At follow-up, the IQ-MI subjects demonstrated decline in memory, visuospatial processing, and phonemic fluency, and 6 of 10 had progressed to a CDR of 0.5, while the IQ-MN subjects did not show decline. The IQ-MI group had significantly lower perfusion than the IQ-MN group in parietal0precuneus, temporal, and opercular frontal regions. In contrast, higher perfusion was observed in IQ-MI compared with IQ-MN in the left medial frontal and rostral anterior cingulate regions. IQ-adjusted memory impairment in individuals with high cognitive reserve is associated with baseline SPECT abnormality in a pattern consistent with prodromal AD and predicts subsequent cognitive and functional decline. (JINS, 2007, 13, 821-831.)

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Section: Dm Rentz Et Alsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Intelligence quotient–adjusted memory impairment is associated with abnormal single photon emission computed tomography perfusion

Rentz

Huh

Sardinha

et al. 2007

J. Inter. Neuropsych. Soc.

View full text Add to dashboard Cite

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“…More recently, PET and SPECT have been used to examine subjects with genetic predisposition to AD, family history of AD, very mild AD, or mild cognitive impairment (MCI) in an attempt to characterize functional patterns associated with preclinical or early disease. The results of these studies suggest a similarity between regions most affected in AD and those regions affected in subjects who have high risk of developing dementia, which suggests that detection of such functional changes may be useful for early detection of AD (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

mentioning

confidence: 95%

Pattern of Cerebral Hypoperfusion in Alzheimer Disease and Mild Cognitive Impairment Measured with Arterial Spin-labeling MR Imaging: Initial Experience

Johnson

Jahng²,

Weiner³

et al. 2005

Radiology

532

390

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PURPOSE-To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethyl-propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations.MATERIALS AND METHODS-Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixedeffects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion. RESULTS-The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P < . 001), bilateral superior and middle frontal gyri (P < .001), and left inferior parietal lobe (P = .007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P < .001) and left (P = .003) and right (P = .012) middle frontal gyri. With a more liberal voxel-level threshold of P < .01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P = .046), similar to the region of greatest significance in the AD group. CONCLUSION-Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.Results of neuropathologic studies suggest that evidence of Alzheimer disease (AD) may be present in the brain years or even decades prior to the onset of clinical symptoms (1,2). Currently, multiple potential therapies are being developed to attempt to halt or disrupt the disease process before neurons are irrevocably lost (3). Evaluation of the effectiveness of these potential treatments will be enhanced by identification of patients at the earliest stages of the disease and by the possibility of objectively measuring disease progression. Because of this,...

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“…Presenilin-1 (PSEN1) mutation carriers develop neuropathologic changes in cortical association areas and subcortical systems, 15 signs and symptoms that can be indistinguishable from those with sporadic AD, with a mean age of 45 at clinical onset. [16][17][18][19] Studies in FAD have demonstrated preclinical changes in morphometry, 20,21 regional brain activation, [22][23][24] functional connectivity, 25 and ERPs. 8,9 ERP preclinical changes have been shown in auditory stimulus discrimination 8 and semantic processing.…”

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confidence: 99%

Event-related potential markers of brain changes in preclinical familial Alzheimer disease

Quiroz

Ally²,

Celone³

et al. 2011

Neurology

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Objectives: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45.Methods: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded.Results: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200-300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. Conclusions:Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD. Neurology Recognition memory impairments in Alzheimer disease (AD) have been linked to neocortical association areas including temporal and parietal lobes.1 Event-related potentials (ERPs) are less expensive, more widely available, and more comfortable than many other imaging modalities (e.g., MRI, PET, SPECT). ERPs, along with other EEG measures, have proven to be a useful marker in neurodegenerative conditions. 2-5 ERP components of recognition memory are sensitive to decline in old age 6 and amnestic mild cognitive impairment (aMCI). 7 Studies have proposed ERPs as a sensitive method for early detection of AD, separating EEG activity related to AD pathology from normal aging. [8][9][10][11][12] Preclinical markers and early detection are increasingly

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Presenilin-1–associated abnormalities in regional cerebral perfusion

Abstract: Regional cerebral perfusion abnormalities based on SPECT are detectable before development of the clinical symptoms of AD in carriers of the PS-1 mutation.

Cited by 69 publications

References 38 publications

Intelligence quotient–adjusted memory impairment is associated with abnormal single photon emission computed tomography perfusion

Intelligence quotient–adjusted memory impairment is associated with abnormal single photon emission computed tomography perfusion

Pattern of Cerebral Hypoperfusion in Alzheimer Disease and Mild Cognitive Impairment Measured with Arterial Spin-labeling MR Imaging: Initial Experience

Event-related potential markers of brain changes in preclinical familial Alzheimer disease

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