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Introduction Recent studies suggest that Alzheimer's disease (AD) biomarker disclosure has no discernable psychological impact on cognitively healthy persons. Far less is known about how such results affect symptomatic individuals and their caregivers. Methods Randomized controlled trial of 82 mild cognitive impairment (MCI) patient and caregiver dyads (total n = 164) to determine the effect of receiving amyloid positron emission tomography results on understanding of, and perceived efficacy to cope with, MCI over 52 weeks of follow-up. Results Gains in the primary outcomes were not consistently observed. Amyloid negative patients reported greater perceived ambiguity regarding MCI at follow-up, while moderate and sustained emotional distress was observed in patients, and to a lesser extent, caregivers, of those who were amyloid positive. There was no corresponding increase in depressive symptoms. Discussion These findings point to the possibility that both MCI patients and caregivers may need emotional support after the disclosure of amyloid scan results.

Objective The objective of this study is to characterize functional competence (measure of assistance needed for independence) on Performance Assessment of Self-Care Skills (PASS) Cognitively Mediated Instrumental Activities of Daily Living (C-IADL), in individuals with amnestic mild cognitive impairment (aMCI). It aims to determine: (1) the association of functional competence on PASS C-IADL tasks with neurocognitive test performance in aMCI, (2) its ability to discriminate individuals with aMCI from healthy control (HC) individuals, and (3) its added value in discriminating aMCI from HC individuals when combined with neurocognitive test performance. Design Cross-sectional secondary analysis of baseline data from a cohort of individuals enrolled in a clinical trial (NCT02386670). Setting Five university-affiliated outpatient clinics in Toronto, Canada. Participants aMCI (N = 137) and HC (N = 51) participants, all aged 60 years or older. Methods We assessed the relationship between functional competence on three C-IADL PASS tasks (shopping, bill paying, and checkbook balancing) and neurocognitive tests in 137 participants with aMCI using multiple linear regressions. Additionally, we constructed receiver operating characteristic curves to assess the role of PASS functional competence in discriminating between 137 aMCI and 51 HC participants. Results Functional competence on PASS was significantly associated with tests of verbal memory, information processing speed, and executive function. It demonstrated 79% accuracy in discriminating aMCI from HC participants. Combining functional competence on PASS with individual neurocognitive tests significantly increased the discriminant accuracy of individual tests, and neurocognitive test scores combined with functional competence on PASS had the highest discriminant accuracy (94%). Conclusion Functional competence on PASS is predicted by the underlying cognitive deficits and possibly captures additional element of effort that could improve the diagnostic accuracy of aMCI when combined with neurocognitive tests. Thus, PASS appears to be a promising tool for assessment of functional competence in aMCI in clinical or research settings. J Am Geriatr Soc 68:1787-1795, 2020.

Introduction The biological mechanisms linking mild cognitive impairment (MCI) and major depressive disorder are not well understood. We investigated whether molecular senescence changes in older adults are associated with a history of major depressive disorder (MDD) or MCI. Methods We included 371 participants: 167 with MCI; 62 cognitively normal with a history of MDD; 97 with MDD+MCI; and 45 cognitively unimpaired (CU) without a history of MDD. The candidate Senescence‐Associated Secretory Phenotype (SASP) biomarkers were measured in the plasma using a customized LUMINEX assay. Results The MDD+MCI group had a higher SASP index than the other groups (P

Objective Older patients with bipolar disorder (BD) present with variable degrees of cognitive impairment. Over time, stress, mood episodes, and comorbidities increase the body's allostatic load. We assessed the extent to which allostatic load vs more traditional measures of medical burden account for the heterogeneity in cognition in this population. Methods Thirty-five older euthymic patients with BD and 30 age-equated, gender-equated, and education-equated comparison participants were administered a comprehensive assessment including a neuropsychological battery, and 9 physiological measures to determine allostatic load. The relationship among allostatic load, medical burden, and cognition was assessed. Results Compared with the mentally healthy comparators, patients were impaired globally, and in 4 cognitive domains-information-processing speed / executive functioning, delayed memory, language, and visuomotor ability, and presented with greater medical burden but not a different allostatic load. Allostatic load, but not medical burden, was associated with delayed memory performance both in a correlational analysis and in a multivariate regression analysis. Conclusion Euthymic older patients with BD are impaired on several cognitive domains and have high medical burden. Their memory performance is more strongly associated with allostatic load than with traditional measures of medical burden. These findings need to be replicated and extended longitudinally.

Objective Eotaxin is a chemokine that exerts negative effects on neurogenesis. We recently showed that peripheral eotaxin levels correlate with both lower gray matter volume and poorer executive performance in older adults with major depressive disorder. These findings suggest that the relationship between eotaxin and set-shifting may be accounted for by lower gray matter volume in specific regions. Prior studies have identified specific gray matter regions that correlate with set-shifting performance, but have not examined whether these specific gray matter regions mediate the cross-sectional association between eotaxin and set-shifting. Method In 27 older adults (mean age: 68 ± 5.2 years) with major depressive disorder, we performed a whole brain (voxel-wise) analysis testing whether/where gray matter density statistically mediates the cross-sectional association of eotaxin and set-shifting performance. Results We found the association between eotaxin and set-shifting performance was fully statistically mediated by lower gray matter density in left middle cingulate, right pre-/post-central, lingual, inferior/superior frontal, cuneus, and middle temporal regions. Conclusion The regions identified above may be both susceptible to a potential neurodegenerative effect of eotaxin, and critical to preserving set-shifting function. Longitudinal and intervention studies are needed to further evaluate whether targeting eotaxin levels will prevent neurodegeneration and executive impairment in older adults with depression. Copyright © 2016 John Wiley & Sons, Ltd.

Objective Several immunological biomarkers are altered in late-life major depressive disorder (LLD). Immunological alterations could contribute to LLD's consequences, but little is known about the relations between specific immunological biomarkers and brain health in LLD. We performed an exploratory pilot study to identify, from several candidates, the specific immunological biomarkers related to important aspects of brain health that are altered in LLD (brain structure and executive function). Methods Adults (n = 31) were at least 60 years old and had major depressive disorder. A multiplex immunoassay assessed 13 immunological biomarkers, and we examined their associations with structural MRI (grey matter volume and white matter hyperintensity volume (WMH)) and executive function (Color–Word Interference and Trail-Making tests) measures. Results Vascular endothelial growth factor (VEGF) and the chemokine eotaxin had significant negative associations with grey matter volume (VEGF: n = 31, r = −0.65; eotaxin: n = 29, r = −0.44). Tumor necrosis factor alpha (TNF-α) had a significant positive relationship with WMHs (n = 30, r = 0.52); interferon-γ (IFN-γ) and macrophage inflammatory protein-1α (MIP-1α) were also significantly associated with WMHs (IFN-γ: n = 31, r = 0.48; MIP-1α: n = 29, r = 0.45). Only eotaxin was associated with executive function (set-shifting performance as measured with the Trail-making test: n = 33, r = −0.43). Conclusions Immunological markers are associated with brain structure in LLD. We found the immunological correlates of grey and white matter differ. Prospective studies are needed to evaluate whether these immunological correlates of brain health increase the risk of LLD's consequences. Eotaxin, which correlated with both grey matter volume and set-shifting performance, may be particularly relevant to neurodegeneration and cognition in LLD. Copyright © 2016 John Wiley & Sons, Ltd.

OBJECTIVE: Cognitive impairment has been associated with late-life suicidal behavior. Without longitudinal data it is unclear whether these are transient features of a depressive state or stable impairments. We examined longitudinally the course of cognitive impairment in older adults with depression and a history of suicide attempt. METHODS: We investigated the persistence of cognitive impairment over time in 198 depressed older adults (age >60); 91 suicide attempters, 39 depressed individuals with suicidal ideation (ideators), and 68 non-suicidal depressed adults assessed over a 2-year period at four time points. We used linear mixed effects modeling to examine group differences in trajectories of cognitive decline over 2 years, using the Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (DRS), and Executive Interview (EXIT). RESULTS: Over the 2-year period, suicide attempters performed significantly worse than both suicide ideators and non-suicidal depressed older adults on the MMSE (mean difference: from ideators: -0.88, p = 0.02; from non-suicidal depressed: -1.52, p CONCLUSIONS: Cognitive impairment in late-life suicidal behavior appears to involve both a stable and a state-related component. Copyright © 2015 John Wiley & Sons, Ltd. Language: en

Background Apathy, or lack of motivation for goal-directed activities, contributes to reduced engagement in and benefit from rehabilitation, impeding recovery from stroke. Objective To examine the effects of strategy training, a behavioral intervention used to augment usual inpatient rehabilitation, on apathy symptoms over the first 6 months after stroke. Design Secondary analysis of randomized controlled trial. Setting Acute inpatient rehabilitation. Participants Participants with acute stroke who exhibited cognitive impairments (Quick Executive Interview Scores ≥3) and were admitted for inpatient rehabilitation were randomized to receive strategy training (n = 15, 1 session per day, 5 days per week, in addition to usual inpatient rehabilitation) or reflective listening (n = 15, same dose). Methods Strategy training sessions focused on participant-selected goals and participant-derived strategies to address these goals, using a global strategy training method (Goal-Plan-Do-Check). Reflective listening sessions focused on participant reflections on their rehabilitation goals and experiences, facilitated by open-ended questions and active listening skills (attending, following, and responding). Main Outcome Measures Trained raters blinded to group assignment administered the Apathy Evaluation Scale at study admission, 3 months, and 6 months. Data were analyzed with repeated-measures fixed-effects models. Results Participants in both groups had similar subsyndromal levels of apathy symptoms at study admission (strategy training, mean=25.79, standard deviation=7.62; reflective listening, mean=25.18, standard deviation=4.40). A significant group × time interaction (F 2,28 = 3.61, P = .040) indicated that changes in apathy symptom levels differed between groups over time. The magnitude of group differences in change scores was large (d = −0.99, t 28 = −2.64, P = .013) at month 3 and moderate to large (d = −0.70, t 28 = −1.86, P = .073) at month 6. Conclusion Strategy training shows promise as an adjunct to usual rehabilitation for maintaining low levels of poststroke apathy.

To examine whether preclinical disability in performance of cognitively focused instrumental activity of daily living (C-IADL) tasks can discriminate between older adults with normal cognitive function and those with mild cognitive impairment (MCI) and, secondarily, to determine the two tasks with the strongest psychometric properties and assess their discriminative ability so as to generate diagnosis-relevant information about cognitive changes associated with MCI and mild neurocognitive disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria.Secondary analyses of cross-sectional data from a cohort of individuals diagnosed with normal cognitive function or MCI.Pittsburgh, Pennsylvania.Older adults with remitted major depression (N = 157).Diagnosis of cognitive status was made at the Alzheimer's Disease Research Center, University of Pittsburgh. Performance on eight C-IADLs was measured using the criterion-referenced, observation-based Performance Assessment of Self-Care Skills (PASS).Ninety-six older adults with normal cognitive function (mean age 72.5 ± 5.9) and 61 with MCI (mean age 75.5 ± 6.3) participated. The eight C-IADLs demonstrated 81% accuracy in discriminating cognitive status (area under the receiver operating characteristic curve (AUC) = 0.81, P.001). Two tasks (shopping and checkbook balancing) were the most discriminating (AUC = 0.80, P.001); they demonstrated similar ability as all eight C-IADLs in determining cognitive status. Assessing performance on these two C-IADLs takes 10 to 15 minutes.This is the first demonstration of the discriminative ability of preclinical disability to distinguish older adults with MCI from cognitively normal older adults. These findings highlight potential tasks that, when measured using the observation-based PASS, demonstrate greater effort for individuals with MCI. These tasks may be considered when attempting to diagnose MCI or mild neurocognitive disorder in clinical practice and research.

BACKGROUND: People who attempt suicide often display cognitive impairments, particularly poor cognitive control. Could poor cognitive control contribute to high suicide rates in old age? A component of cognitive control, cognitive inhibition-active suppression of task-irrelevant processing-is very sensitive to aging and has been linked to attempted suicide. We investigated cognitive inhibition in older high-lethality suicide attempters, closely resembling suicide victims, as well as low-lethality attempters, and control groups with and without depression and suicidal ideation. METHODS: A total of 102 participants aged 60 years and older (17 psychiatrically healthy control subjects, 38 depressed control subjects, 16 suicide ideators, 14 low-lethality suicide attempters, and 17 high-lethality suicide attempters) underwent comprehensive clinical and cognitive assessments. They completed the Delis-Kaplan Executive Function System Color-Word Interference Test, a validated modification of the Stroop test. RESULTS: High-lethality suicide attempters demonstrated a distinct pattern of cognitive inhibition deficits. Compared with psychiatrically healthy control subjects and suicide ideators, high-lethality attempters took longer to complete inhibition trials, even after accounting for potential confounding factors (age, education, Mini mental state examination score, information processing speed, and accuracy). Compared with non-suicidal depressed and healthy control subjects, low-lethality suicide attempters committed more uncorrected errors; however, this difference was not specific to the inhibition condition. CONCLUSIONS: Older suicide attempters are a cognitively heterogeneous group. Poor cognitive control in high-lethality attempters may undermine their ability to solve real-life problems, precipitating a catastrophic accumulation of stressors. Meanwhile, low-lethality attempters' poor performance may reflect a careless approach to the task or faulty monitoring. Copyright © 2014 John Wiley & Sons, Ltd. Language: en

Objective We evaluated the feasibility of a trial of Wii interactive video gaming, and its potential efficacy at improving cognitive functioning compared to health education, in a community sample of older adults with neuropsychologically defined mild cognitive impairment (MCI).

Objective Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects; (ii) whether IL-1RA was associated with worse neurocognitive function; and (iii) whether IL-1RA was associated with white matter integrity. Methods Twenty-one euthymic BD patients (65 +/− 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis-derived z-scores and a global z-score were obtained from a battery of 21 neurocognitive tests. Diffusion tensor images were used to obtain fractional anisotropy (FA), and an automated labeling pathway algorithm was used to obtain white matter hyperintensity burden. Results Interleukin-1 receptor antagonist was elevated in BD subjects compared with controls (439+/−326 pg/mL vs. 269+/−109 pg/mL; p = 0.004). Moreover, IL-1RA was inversely correlated with three cognitive function factors and global cognition (r = −0.37; p = 0.01). IL-1RA continued to correlate with global cognitive function even when covarying for either IL-6 or brain-derived neurotrophic factor. Although FA was lower in BD subjects (0.368 +/− 0.02 vs. 0.381 +/− 0.01; p = 0.02), IL-1RA was not associated with FA or white matter hyperintensity burden. Conclusion Elevated serum levels of IL-1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co-occurring increases in IL-6, by decreased brain-derived neurotrophic factor, nor by measures of white matter integrity. These cross-sectional findings support the possibility that the IL-1 family may contribute to cognitive impairments in BD. Copyright © 2013 John Wiley & Sons, Ltd.

Objectives Cognitive dysfunction is prevalent in older adults with bipolar disorder (BD). High white matter hyperintensity (WMH) burden, a marker of white matter disease, detected on T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) has been consistently reported in BD across all age ranges, including older adults. Yet, whether high WMH burden is related to the excess cognitive impairment present in older adults with BD is unknown. Therefore, we examine whether higher WMH burden is related to worse cognitive function in older adults with BD. Methods This is a cross-sectional study of 27 non-demented BD patients aged ≥50 years and 12 similarly aged mentally healthy comparators (controls). Subjects underwent both brain MRI and comprehensive neurocognitive assessment. We employed correlational analyses to evaluate the burden of WMH and the relationship between WMH and cognitive function. Results Although BD subjects had worse performance in all cognitive domains, BD subjects had less total WMH burden (t[13.4] = −3.57, p = 0.003). In control subjects, higher WMH was related to lower global cognitive function (ρ = −0.57, n = 12, p = 0.05). However, WMH did not correlate with neuropsychological performance in BD subjects. Further, BD and control subjects did not differ with respect to total gray and hippocampal volumes. Conclusions Cognitive dysfunction in late-life BD does not appear to be due primarily to processes related to increased WMH or reduced gray matter volume. Future longitudinal studies should examine other potential neuroprogressive pathways such as inflammation, mitochondrial dysfunction, serum anticholinergic burden, and altered neurogenesis. Copyright © 2013 John Wiley & Sons, Ltd.

In late life, bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction even when patients are euthymic (1–6). Both disorders are also associated with increased rates of dementia (7, 8). In addition to impaired cognitive function, these disorders may interfere with everyday functional abilities (9). Whether BD and MDD have similar or different cognitive profiles and levels of impairment in older age is not clear. Identifying whether there are relevant differences may help in understanding the neurobiology of these illnesses and developing specific interventions for BD or MDD to prevent, halt, or remediate cognitive impairment and functional decline. For example, deficits in memory may require different treatments than deficits in executive function. Additionally, if both disorders are associated with comparable levels of cognitive function, but differing levels of everyday functional ability, interventions might need to consider targets other than cognition to enhance everyday function (10). In this report, our primary aim was to examine the overall patterns of cognitive function in patients with BD and MDD. Our main hypothesis was that among older adults, BD and MDD would be associated with a similar pattern of deficits, primarily in information processing speed and executive function; however, the level of cognitive impairment would be more severe in individuals with BD. We also predicted that instrumental activities of daily living (IADLs) would be directly related to cognitive performance, most significantly with Information Processing Speed and Executive Function, and IADLs would be more impaired in subjects with BD. These hypotheses were based on our prior reports and the current literature concerning neurodegeneration in BD (11). Exploratory analyses were conducted to examine the relationship of cognition with lifetime history of psychosis and lifetime duration of illness since history of psychosis and longer duration of illness have been associated with worse cognitive function (12).

Objective Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl- D-aspartate-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore, we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery. Method We recruited subjects aged 60 years and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10 mg/d for 1 week, then 10 mg twice daily) or placebo, for 12 weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes. Results Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12 week randomized controlled trial. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome. Conclusion Memantine was not associated with superior affective or functional outcome compared with placebo in medically rehabilitating older adults with depressive and apathy symptoms. Copyright © 2011 John Wiley & Sons, Ltd.

Objective Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function. Methods We examined 60 adults aged 60 years and older, who took part in a 12-week trial of escitalopram versus placebo for generalized anxiety disorder. All subjects had pre-treatment and post-treatment assessments that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation. Results Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory but no association with executive tasks (measures of working memory and set shifting). Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes: memory improvement was seen with cortisol reduction among patients receiving escitalopram but not among patients receiving placebo. Conclusion Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of generalized anxiety disorder predicted changes in immediate and delayed memory. This finding suggests a novel treatment strategy in late-life anxiety disorders: targeting hypothalamic–pituitary– adrenal axis dysfunction to improve memory. Copyright © 2011 John Wiley & Sons, Ltd.

Cognitive impairment is a common sequela in acquired brain injury and one that predicts rehabilitation outcomes. There is emerging evidence that impairments in cognitive functions can be manipulated by both pharmacologic and nonpharmacologic interventions to improve rehabilitation outcomes. By using stroke as a model for acquired brain injury, we review the evidence that links cognitive impairment to poor rehabilitation outcomes and discuss possible mechanisms to explain this association. Furthermore, we examine nascent promising research that suggests that interventions that target cognitive impairments can lead to better rehabilitation outcomes.

More than half of the older adults respond only partially to first-line antidepressant pharmacotherapy. Our objective was to test the hypothesis that a depression-specific psychotherapy, Interpersonal Psychotherapy (IPT), when used adjunctively with escitalopram, would lead to a higher rate of remission and faster resolution of symptoms in partial responders than escitalopram with depression care management (DCM).We conducted a 16-week randomized clinical trial of IPT and DCM in partial responders to escitalopram, enrolling 124 outpatients aged 60 and older. The primary outcome, remission, was defined as three consecutive weekly scores of 7 or less on the Hamilton rating scale for depression (17-item). We conducted Cox regression analyses of time to remission and logistic modeling for rates of remission. We tested group differences in Hamilton depression ratings over time via mixed-effects modeling.Remission rates for escitalopram with IPT and with DCM were similar in intention-to-treat (IPT vs. DCM: 58 [95% CI: 46, 71] vs. 45% [33,58]; p = 0.14) and completer analyses (IPT vs. DCM: 58% [95% CI: 44,72] vs. 43% [30,57]; p = 0.20). Rapidity of symptom improvement did not differ in the two treatments.No added advantage of IPT over DCM was shown. DCM is a clinically useful strategy to achieve full remission in about 50% of partial responders.

The amygdalae have been a focus of mood disorder research due to their key role in processing emotional information. It has been long known that depressed individuals demonstrate impaired functional performance while engaged in emotional tasks. The structural basis for these functional differences has been investigated via volumetric analysis with mixed findings. In this study, we examined the morphometric basis for these functional changes in late-life depression (LLD) by analyzing both the size and shape of the amygdalae with the hypothesis that shape differences may be apparent even when overall volume differences are inconsistent.Magnetic resonance imaging data were acquired from 11 healthy, elderly individuals and 14 depressed, elderly individuals. Amygdalar size was quantified by computing total volume and amygdalar shape was quantified with a shape analysis method that we have developed.No significant volumetric differences were found for either amygdala. Nevertheless, localized regions of significant shape variation were detected for the left and right amygdalae. The most significant difference was contraction (LLD subjects as compared to control subjects) in a region typically associated with the basolateral nucleus, which plays a key role in emotion recognition in neurobiologic models of depression.In this LLD study, we have shown that, despite insignificant amygdalar volumetric findings, variations of amygdalar shape can be detected and localized. With further investigation, morphometric analysis of various brain structures may help elucidate the neurobiology associated with LLD and other mood disorders.

Objective and Methods The neurobiology of late-life anxious depression (LLAD) is poorly characterized despite evidence that this is a common and severe subtype of late-life depression. To identify the neuroanatomical substrate of LLAD, we examined event-related fMRI data collected in eight subjects with late-life depression, half of whom had high levels of comorbid anxiety. Subjects were trained on the Preparing to Overcome Prepotency (POP) task, which is an executive control task that reliably activates the lateral prefrontal cortex–anterior cingulate cortex (ACC) cognitive control circuit. Results Time series analysis showed that, when compared with elderly depressed subjects, elderly subjects with anxious depression performing the POP task produced a significantly greater and more sustained signal in three regions: BA24 (dorsal anterior cingulate), BA31 (posterior cingulate), and BA6 (prefrontal cortex). While elderly subjects with pure depression presented a bimodal activation curve in the dorsal anterior cingulate and the posterior cingulate, elderly subjects with anxious depression presented a sustained unimodal activation pattern. Conclusions Our preliminary results suggest specific activation patterns unique to anxious depression that may suggest greater and more sustained efforts of the ACC to carry out cognitive control tasks. Further research is needed to clarify the neuroanatomical basis of LLAD. Copyright © 2009 John Wiley & Sons, Ltd.

SUMMARY Objective To explore clinical and treatment-response variability in late-onset vs early-onset non-bipolar, non-psychoticmajor depression.Methods We grouped patients from a late-life depression treatment study according to illness-course characteristics: thosewith early-onset, recurrent depression (n¼59), late-onset, recurrent depression (n¼27), and late-onset, single-episodedepression (n¼95). Early-onset was defined as having a first lifetime episode of major depression at age 59 or earlier;late-onset was defined as having a first episode of major depression at age 60 or later. We characterized the three groupsof patients with respect to baseline demographic, neuropsychological, and clinical characteristics, use of augmentation phar-macotherapy to achieve response, and treatment outcomes.Results Rates of response, remission, relapse, and termination were similar in all three groups; however, patients with late-onset, recurrent major depression took longer to respond to treatment than those with late-onset, single-episode depression(12 weeks vs 8 weeks) and had more cognitive and functional impairment. Additionally, patients with recurrent depression(whether early or late) were more likely to require pharmacotherapy augmentation to achieve response than patients with asingle lifetime episode.Conclusion Late-onset, recurrent depression takes longer to respond to treatment than late-onset single-episode depres-sion and is more strongly associated with cognitive and functional impairment. Further study of biological, neuropsycho-logic, and psychosocial correlates of late-onset, recurrent depression is needed. Copyright # 2005 John Wiley & Sons, Ltd.key words—major depression; late-onset; treatment outcome

Objective The increased resistance of better-educated individuals to the cognitive effects of neuropathology has been conceptualized as reflecting brain reserve. This study examined whether educational level influences the degree of neuropsychological impairment associated with late-life depression. Methods The neuropsychological performances of 115 older depressed patients and of 44 comparison subjects of similar age and education were compared as a function of educational level. Results While depressed patients performed worse than comparison subjects on all the measures, the severity of this impairment (with respect to comparison subjects) did not differ with the educational level of the patients. Conclusions Brain reserve, as indexed by the patients' level of education, does not mitigate the cognitive decrements associated with late-life depression. Copyright © 2005 John Wiley & Sons, Ltd.

Background: The older alcoholic has been distinguished from the younger alcoholic with regard to both the acute effects of alcohol and also the recovery of functioning with abstinence. Few studies, however, have included samples of exclusively older subjects. In this investigation we examined the recovery of functioning in an older cohort of recovering alcoholics (age range 55–83) to determine which neuropsychological functions improve and which remain impaired with abstinence. Methods: We used a cross-sectional design, comparing three demographically matched groups on a battery of neuropsychological tests: (a) older alcoholics who had been abstinent for greater than 6 months, (b) older alcoholics who had been abstinent for less than 6 months, and (c) a control group of older subjects without alcohol abuse histories. Results: In almost all tasks, the alcoholics who were abstinent for less than 6 months performed worse than the control group. In contrast, the alcoholics who had been abstinent for more than 6 months differed from the control group on learning and recall of a word list, immediate and delayed recall of a complex figure, initial letter fluency, and clock drawing. Conclusions: Memory and executive skills appear to be resistant to recovery or at least slower to recover with abstinence in the older alcoholic. The impairment with visuospatial skills reported in prior investigations of alcoholics may be related to compromised executive functions, which interfere with the encoding of more complex visuospatial information and thus affect recall of such information. Studies that involve larger samples of older alcoholics are needed to understand their ability to recover cognitive functioning with abstinence.