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Alireza Atri

Publications and source records attributed to Alireza Atri.

7 recordsLinked to original sources
PubMed2006

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

Aged↗
PubMed2005

Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans.

Recent computational modeling and slice physiology studies have suggested that long-term encoding may depend on sustained spiking during brief memory delays in parahippocampal neurons, and that this persistent spiking activity is modulated by effects of acetylcholine at muscarinic receptors. Our recent functional magnetic resonance imaging (fMRI) study has shown that sustained parahippocampal delay period activity during delayed match-to-sample performance in healthy young individuals predicted subsequent memory of visual stimuli on a recognition memory assessment 20 min later (Schon et al., 2004). The current study combined this fMRI paradigm with a pharmacological manipulation to test whether this long-term encoding-related delay activity is reduced in subjects who receive the muscarinic cholinergic antagonist scopolamine before fMRI scanning. Subsequent memory was predicted by sustained activity during brief memory delays bilaterally in the perirhinal/entorhinal cortex, in the right posterior parahippocampal and mid-fusiform gyri, and in the hippocampal body in healthy young individuals without a scopolamine challenge. This activity was reduced in subjects receiving scopolamine. The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine.

Analysis of Variance↗
PubMed2005

Prevalence and effects of lobar microhemorrhages in early-stage dementia.

BACKGROUND: 80-100% of patients with Alzheimer's disease have vascular pathology related to cerebral amyloid angiopathy (CAA), and 5-7% have CAA-related lobar microhemorrhages (LMH) at autopsy. The prevalence and effects of LMH detectable by gradient echo MRI (GE-MRI) in early-stage dementia are unknown. OBJECTIVE: To obtain, using GE-MRI, a prevalence estimate for LMH in patients with early-stage dementia and to assess the effects of LMH on dementia severity. METHODS: Eighty-four subjects aged >or=55 years (range 58-89; mean 76) underwent cognitive and GE-MRI evaluation. The 84 subjects consisted of 61 consecutive subjects evaluated as part of an initial clinical evaluation for dementia and 23 consecutively evaluated healthy older subjects (controls). Data were analyzed for presence and number of LMH on GE-MRI and the effect of number of LMH on dementia severity. RESULTS: Nine (15%) of the 61 dementia patients versus 1 (4%) of the 23 control subjects demonstrated LMH on GE-MRI. Multiple (>or=2) LMH were found in 7 of the 9 (88%) dementia subjects with LMH (range of LMH counts 1-330) and no (0%) control subjects. Multivariable causal modeling indicated that number of LMH (p < 0.02), age (p < 0.01) and duration of symptoms (p < 0.001) significantly increased dementia severity while higher educational level (p < 0.001) was protective. CONCLUSIONS: LMH were detected by GE-MRI in 15% of patients with early-stage dementia and may contribute to dementia severity.

Aged↗
PubMed2004

Blockade of central cholinergic receptors impairs new learning and increases proactive interference in a word paired-associate memory task.

Experimental data and computational models suggest that blockade of muscarinic cholinergic receptors impairs paired-associate learning and increases proactive interference (E. DeRosa & M. E. Hasselmo, 2000; M. E. Hasselmo & J. M. Bower, 1993). The results presented here provide evidence in humans supporting these hypotheses. Young healthy subjects first learned baseline word pairs (A-B) and, after a delay, learned additional overlapping (A-C) and nonoverlapping (D-E) word pairs. As predicted, when compared with subjects who received the active placebo glycopyrrolate (4 microg/kg) and subjects who were not injected, those who received scopolamine (8 microg/kg) showed (a) overall impairment in new word paired-associate learning, but no impairment in cued recall of previously learned associates; and (b) greater impairment in learning overlapping (A-C) compared with nonoverlapping (D-E) paired associates.

Adolescent↗
PubMed2004

Thyroid nodule shape and prediction of malignancy.

BACKGROUND: Thyroid nodules are common; the vast majority benign. Preoperative determination of malignancy remains imprecise, despite fine-needle aspiration (FNA). Numerous risk factors have been proposed for predicting malignancy, though few have been found useful. Oxygen delivery is a crucial component for tumor cell growth. It has been hypothesized that malignant tumors may configure their shape to maximize access to local nutrient delivery. Mathematically, surface area to volume is maximized by a spherical shape. We sought to determine if spherical shape is a predictor of malignancy. METHODS: Seven hundred forty-seven consecutive patients underwent ultrasound evaluation and FNA of 993 solid thyroid nodules (< 25% cystic) between 1995 and 2000 and were retrospectively analyzed. Nodules were classified as benign or malignant based on FNA and/or surgical pathology. Spherical shape was estimated by calculating a ratio of the longest to shortest dimensions, and rate of malignancy correlated. RESULTS: Spherical shape was independently correlated with risk of malignancy (p < 0.001). Thyroid cancer was detected in 11% of all nodules, but ranged from 18% in spherical nodules to 5% in those least spherical. Nodules found to have suspicious or intermediate cytology showed similar variation in malignant risk. A long to short axis ratio greater than 2.5 was 100% predictive of a benign process, although present in only 4% of our cohort. A prospective validation was performed and confirmed consistent results (p < 0.01). CONCLUSION: Spherical shape is associated with an increased rate of malignancy in solid thyroid nodules. Determination of shape may assist in clinical risk assessment of thyroid cancer.

Adult↗
PubMed2003

Scopolamine impairs human recognition memory: data and modeling.

Eight subjects studied a set of complex visual images after administration of 0.4 mg scopolamine. Another 8 subjects performed the same task without drug administration. On a subsequent item recognition test, subjects rated, on a 5-point scale, their confidence that the studied pictures and an equal number of unstudied lures were actually presented. Results showed that scopolamine affected responses to studied items, but not unstudied lures, demonstrating an unambiguous effect of scopolamine on recognition memory. To describe the scopolamine-injected subjects' data, the authors constructed a new model of 2-process recognition that includes the A. P. Yonelinas (1994) model as a limiting case. The model analysis suggests that scopolamine affected both familiarity and recollection. In particular, scopolamine did not affect the frequency with which recollection took place, but rather, affected the amount of recollected information.

Adult↗