Biomedical subjects

Howard J Aizenstein

Publications and source records attributed to Howard J Aizenstein.

8 recordsLinked to original sources

PubMed2005

Prefrontal and striatal activation during sequence learning in geriatric depression.

BACKGROUND: Frontostriatal dysfunction is a primary hypothesis for the neurocognitive changes of depression in late life. The aim of the present study was to test this hypothesis with the use of functional magnetic resonance imaging (fMRI) tasks that are known to engage the prefrontal and neostriatal cognitive circuits. METHODS: Twenty-three elderly subjects (mean age, 69.9 years) participated: 11 subjects with a current major depressive episode and 12 nondepressed elderly control subjects. Subjects underwent fMRI while performing a concurrent implicit and explicit sequence learning task. Region of interest (ROI)-based analyses were conducted, focusing on the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the neostriatum. RESULTS: As expected, both the control and depressed subjects learned the sequence during both implicit and explicit conditions. During explicit learning, decreased prefrontal activation was found in the depressed subjects, along with increased striatal activation. The increased striatal activity in the depressed subjects was due to increased activity on the trials that violated the sequence. During implicit learning, no significant differences were found between the groups in the identified ROIs. CONCLUSIONS: The increased striatal activation on trials that violated the sequence demonstrates a greater response to negative feedback for depressed compared with control subjects. Our observations of significant differences in both prefrontal and striatal regions in the depressed elderly subjects relative to elderly control subjects supports the frontostriatal dysfunction hypothesis of late-life depression.

Aged↗

PubMed2005

Prefrontal and striatal activation in elderly subjects during concurrent implicit and explicit sequence learning.

Decreased function in the prefrontal cortex (PFC) is regarded as a primary mechanism of cognitive aging. However, despite a strong association between the prefrontal cortex and the neostriatum, the role of the neostriatum in cognitive aging is less certain. In the current study, event-related functional MRI was used to distinguish the cognitive contributions of neostriatal and prefrontal function in elderly versus young subjects. Twenty healthy subjects, 9 elderly (mean age 67.6 years), and 11 young (mean age 22 years) performed a concurrent implicit and explicit sequence learning task while undergoing functional MR imaging. Both groups showed learning in both the implicit and explicit task conditions. Relative to the young subjects, the elderly subjects showed decreased activation in the left PFC during both implicit and explicit learning, decreased activation in the right putamen during implicit learning, and increased activation in the right PFC during explicit learning. Our results support the theory that changes in a network of brain regions, including the dorsolateral prefrontal cortex and the striatum, are related to cognitive aging. Moreover, these changes are observed during an implicit task, and thus do not seem to be mediated by awareness.

Adult↗

PubMed2005

Event-related functional magnetic resonance imaging investigation of executive control in very old individuals with mild cognitive impairment.

BACKGROUND: Attentional control of executive cognitive function (ECF) decreases in older individuals with Alzheimer Disease (AD). In order to examine early AD-related changes in the neural substrates of ECF attentional control, we measured activation dorsolateral prefrontal (dLPFC), posterior parietal (PPC), and anterior cingulate cortex (ACC) in adults with mild cognitively impairment (MCI) and in cognitively normal (CN) adults. METHODS: Functional magnetic resonance imaging analysis of brain activation in MCI (n = 8, mean age 79.5) and CN (n = 8 mean age 81.5) during increasing loads of attentional demands. RESULTS: MCI and CN older adults performed with similar accuracy and reaction time. MCI had greater activation than CN in PPC (right p = .03 and left p = .05) and dlPFC areas (right p = .002 and left p = .004), while activation in ACC was similar in the two groups. Response to increasing loads of the task differed by group: MCI selectively engaged bilateral PPC (right p = .03, left p = .04), while CN subjects increased bilateral dlPFC activation (right p = .005 and left p = .02) and ACC activation (p = .04). Among MCI, greater load-related changes in PPC activity were associated with smaller load-related changes in accuracy rates (r = -.85, p = .07) and greater increases in reaction times (r = .97, p = .01). In CN subjects, load-related change in PPC activation was associated with load-related change in reaction time (r = .76, p = .02) but not with changes in accuracy rates. CONCLUSIONS: PPC and dlPFC may show early functional changes associated with MCI.

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PubMed2005

Trajectories of treatment response in late-life depression: psychosocial and clinical correlates.

The authors examined the effect of psychosocial and clinical variables on treatment response trajectory in elderly patients with major depressive disorder. Three studies provided data on treatment response in 360 elderly depressed subjects who participated in protocols using either nortriptyline or paroxetine as monotherapy or, in 2 studies, combined with interpersonal psychotherapy. Treatment response was assessed with the Hamilton Rating Scale for Depression-17 Item (HRSD-17) score over 12 weeks of acute treatment in each study. The mixture-modeling method of trajectory analysis was used to identify different subpopulations of response, and to determine whether baseline HRSD-17 score, depressive illness course (single or recurrent), current episode duration, Interpersonal Self Evaluation List-Self-esteem factor, age at study entry, and medical burden were risk factor covariates associated with response trajectory. As a contrast, logistic regression was used to assess the association between the same covariates and the probability of response (defined as HRSD-17 < or =10 and 50% reduction from baseline). In each study, there were 2 response trajectories with similar course, but with different speed. We classified the trajectories as "rapid response" and "slower response." Baseline HRSD-17 score was a significant predictor of response trajectory, with higher initial score related to slower response trajectory. Higher self-esteem was associated with more rapid response trajectory. In the logistic regression analysis, in two of the studies, higher baseline HRSD-17 score was a significant risk factor for nonresponse. In the study without psychotherapy, higher self-esteem was associated with responding to treatment. Thus, trajectory analysis can identify different trajectories of responders and determine psychosocial and clinical variables associated with response trajectory in the acute treatment of geriatric depression. Further study focusing on risk factors associated with slower response may help optimize treatment in elderly patients who do not respond quickly to first-line therapies.

Age Factors↗

PubMed2004

Prevalence of cognitive disorders differs as a function of age in HIV virus infection.

OBJECTIVES: Ten per cent of all new cases of AIDS in the United States are in persons older than 50 years. This is particularly problematical in the case of the neuropsychiatric consequences of HIV, because there are neuropsychiatric disorders which become common in older individuals in the absence of HIV. The purpose of this report is to describe the prevalence and incidence of cognitive impairment in HIV-infected individuals enrolled in a community-based study. DESIGN: The study consisted of community-based, sentinel survey physician referrals of HIV-infected patients, with volunteer recruitment of risk-appropriate seronegative controls. One-year longitudinal follow-up study. METHODS: Detailed neuropsychiatric evaluations were performed at study entry and after one year. A brief, interim visit tracked incident change. Each subject's neuropsychological test performance was classified as normal, demented, or cognitive impairment (not demented). RESULTS: The prevalence of cognitive disorder among HIV-positive individuals over 50 years was significantly greater than in individuals younger than 50 years. Among older participants, dementia was the more common classification (23%), whereas among younger participants, a milder form of cognitive impairment was more prevalent (22%). Alcohol abuse/dependence was a significant risk factor for a disorder, whereas greater education was a protective factor. The one-year incidence of disorder in the sample overall was low (7.3%), and age was not a significant risk factor. However, HIV viral load at study entry was significantly higher among those participants who had developed cognitive impairment one year later. CONCLUSION: Age is a significant risk modifier for prevalent neuropsychological disorder.

Activities of Daily Living↗

PubMed2004

Regional brain activation during concurrent implicit and explicit sequence learning.

We used event-related fMRI to identify the brain regions engaged during explicit and implicit sequence learning (ESL and ISL, respectively). Twenty-four subjects performed a concurrent ESL and ISL task. Behavior showed learning in both conditions. Prefrontal (PFC), striatal, anterior cingulate cortex (ACC) and visual regions (V1, V2 and V3) were engaged during both ESL and ISL. With ESL there was increased activity in the visual regions on the predictable (i.e. learned pattern) trials. With ISL, however, there was a relative decrease in activity in visual regions. The opposite patterns in the visual regions highlight the different effects of ESL and ISL. The learning process was distinguished from the result of learning, by fitting subjects' functional magnetic resonance imaging data to their learning curve. This analysis revealed more extensive PFC activity during ESL and caudal ACC activity specific for the result of learning analysis, when the expected response was violated. Our results suggest a relative dissociation of the brain regions engaged during ESL and ISL, whereby ESL and ISL can be viewed as partially distinct but overlapping parallel processes.

Adolescent↗

PubMed2004

The BOLD hemodynamic response in healthy aging.

Several previous studies have compared the blood oxygen level-dependent (BOLD) hemodynamic response (HDR) in healthy elderly subjects to the HDR in young subjects. Some studies have found a relative decreased amplitude in the elderly in the visual cortex, whereas other studies have found the elderly HDR amplitude in the visual cortex to be nearly identical to that in young subjects. A possible explanation for the different findings is that the peak voxel HDR is similar between the groups, but that the HDR in the group-averaged region-of-interest (ROI) is "washed out" by the inclusion of less significant voxels (due to a smaller extent of activation in the elderly) or by the inclusion of negative-peaking voxels. We tested this hypothesis using event-related functional magnetic resonance imaging (fMRI ). While undergoing fMRI, subjects performed a simple visual and motor task, pressing with their index fingers in response to visual presentation of the word tap. Data from 18 subjects, 8 young and 10 elderly, were analyzed. For each subject, a visual and a motor ROI was selected by choosing the most significant positive voxels within the anatomically defined ROI. This individual subject approach excluded both low-significance and negative-peaking voxels. Similar peaks were found for the elderly and the young subjects in both motor and visual regions and a more sustained BOLD response was found for the elderly in both regions. Additionally, as predicted, a greater percentage of voxels with a negative HDR was found for the elderly in the visual region; this finding was also replicated in our reanalysis of an independent fMRI and aging study from the fMRI Data Center. Functional neuroimaging observations of negative HDRs in visual areas have been interpreted as the effect of unconstrained processing during rest. Our results suggest that the elderly may have more unconstrained visual processing during the rest condition in the scanner. The observation that the group differences in the BOLD response are sensitive to voxel selection (e.g., inclusion of low-significance and/or negative voxels) underscores the importance of ROI selection criteria in the interpretation of fMRI studies using elderly populations.

Adult↗

PubMedDate not supplied

Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype.

OBJECTIVE: Psychotic symptoms occur in 30%-60% of individuals with Alzheimer disease (AD) with psychosis (AD+P). AD+P identifies a distinct AD phenotype, with increased severity of cognitive impairment and a more rapid cognitive decline. Using factor and cluster analysis, we previously proposed two subtypes of patients with AD+P, one characterized by misidentifications and hallucinations (Misidentification), the other by persecutory delusions (Paranoid). We hypothesized that these two groups differed in their patterns of cognitive impairment, compared with AD subjects without psychosis. METHODS: Subjects (N=119) with possible or probable AD were assessed with a comprehensive neuropsychological test battery at the time of initial presentation. Psychotic symptoms were ascertained with the CERAD Behavioral Rating Scale. Cognitive test scores were compared among groups by use of general linear-regression models, with age, education, and duration of illness entered as covariates. All results were corrected for multiple comparisons. RESULTS: The Misidentification group was significantly more impaired than the Non-Psychotic group on tests of verbal fluency and visuospatial function. The Paranoid group did not differ from the Non-Psychotic group on any test. CONCLUSIONS: These results support the identification of the Misidentification and Paranoid groups as distinct subgroups of AD+P. The ability to detect meaningful biologic associations of AD+P in future studies would be enhanced by separate analysis of the Misidentification and Paranoid phenotypes.

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