Socioemotional Dysfunction From Temporal Lobe Involvement in Frontotemporal Dementia: A Preliminary Report.

OBJECTIVE: Socioemotional changes, rather than cognitive impairments, are the feature that defines behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed the socioemotional changes in bvFTD and other dementias to frontal lobe dysfunction; however, recent work implies a further contribution from right anterior temporal disease. The authors evaluated relationships between regional brain atrophy and socioemotional changes in both bvFTD and early-onset Alzheimer's disease (EOAD). METHODS: This study explored the neuroanatomical correlations of performance on the Socioemotional Dysfunction Scale (SDS), an instrument previously shown to document socioemotional changes in bvFTD, among 13 patients with bvFTD not preselected for anterior temporal involvement and 16 age-matched patients with early-onset Alzheimer's disease (EOAD). SDS scores were correlated with volumes of regions of interest assessed with tensor-based morphometric analysis of MRI images. RESULTS: As expected, the bvFTD group had significantly higher SDS scores overall and smaller frontal regions compared with the EOAD group, which in turn had smaller volumes in temporoparietal regions. SDS scores significantly correlated with lateral anterior temporal lobe (ATL) atrophy, and a regression analysis that controlled for diagnosis indicated that SDS scores predicted lateral ATL volume. Within the bvFTD group, higher SDS scores were associated with smaller lateral and right ATL regions, as well as a smaller orbitofrontal cortex. Within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex. CONCLUSIONS: This study confirms that, in addition to orbitofrontal disease, there is a prominent right and lateral ATL origin of socioemotional changes in bvFTD and further suggests that right parietal involvement contributes to socioemotional changes in EOAD.

Video telehealth emotional awareness and expression therapy for older U.S. military veterans with chronic pain: A pilot study.

OBJECTIVES: Emotional Awareness and Expression Therapy (EAET) targets trauma and emotional conflict to reduce or eliminate chronic pain, but video telehealth administration is untested. This uncontrolled pilot assessed acceptability, feasibility, and preliminary efficacy of group-based video telehealth EAET (vEAET) for older veterans with chronic musculoskeletal pain. METHODS: Twenty veterans were screened, and 16 initiated vEAET, delivered as one 60-minute individual session and eight 90-minute group sessions. Veterans completed posttreatment satisfaction ratings and pain severity (primary outcome), pain interference, anxiety, depression, functioning, social connectedness, shame, and anger questionnaires at baseline, posttreatment, and 2-month follow-up. RESULTS: Satisfaction was high, and veterans attended 7.4 (SD = 0.6) of 8 group sessions; none discontinued treatment. Veterans attained significant, large reductions in pain severity from baseline to posttreatment (p < .001, Hedges' g = -1.54) and follow-up (p < .001, g = -1.20); 14 of 16 achieved clinically significant (≥ 30%) pain reduction, and 3 achieved 90-100% pain reduction. Secondary outcomes demonstrated significant, medium-to-large improvements. CONCLUSIONS: In this small sample, vEAET produced better attendance, similar benefits, and fewer dropouts than in-person EAET in prior studies. Larger, controlled trials are needed. CLINICAL IMPLICATIONS: Group vEAET appears feasible and highly effective for older veterans with chronic pain.

Physical Function Effects of Live Video Group Exercise Interventions for Older Adults: A Systematic Review and Veteran's Gerofit Group Case Study.

Background: Literature on telehealth interventions for older adults has been primarily on asynchronous interventions. During the COVID-19 pandemic, older adult exercise programs transitioned to an online format. This systematic review and case study examines the effectiveness of older adult live video exercise group interventions on physical health with insights from a Los Angeles VA program, Gerofit. Methods: PubMed was searched for live video older adult exercise groups from database inception to November 2021. All eligible studies included assessments of physical health and were limited to participants with an average age of 65 years or greater. Ten Veterans, who had participated in both in-person and virtual Gerofit sessions, were surveyed in the case study. Results: Nine studies met the inclusion criteria. Four studies included an equivalent in-person group as a comparator to the live video group and reported no significant between-group differences in outcomes, including energy expenditure and 6-minute walking distance test (6MWD). The other five studies reported statistically significant in-group improvement in outcomes including isokinetic knee strength. Case study participants reported similar attendance rates and perceived benefits, such as improved balance, when comparing virtual and in-person sessions. Discussion: Live video exercise groups in older adults demonstrated an improvement in physical function that was not statistically different from the comparison in-person sessions with the added benefit of averaging a higher attendance rate, providing initial support for the use of live video in older adult exercise programs. Insights from the case study supplement this by demonstrating older adults' positive attitude on these groups.

Education differentially contributes to cognitive reserve across racial/ethnic groups.

INTRODUCTION: We examined whether educational attainment differentially contributes to cognitive reserve (CR) across race/ethnicity. METHODS: A total of 1553 non-Hispanic Whites (Whites), non-Hispanic Blacks (Blacks), and Hispanics in the Washington Heights-Inwood Columbia Aging Project (WHICAP) completed structural magnetic resonance imaging. Mixture growth curve modeling was used to examine whether the effect of brain integrity indicators (hippocampal volume, cortical thickness, and white matter hyperintensity [WMH] volumes) on memory and language trajectories was modified by education across racial/ethnic groups. RESULTS: Higher educational attainment attenuated the negative impact of WMH burden on memory (ß = -0.03; 99% CI: -0.071, -0.002) and language decline (ß = -0.024; 99% CI:- 0.044, -0.004), as well as the impact of cortical thinning on level of language performance for Whites, but not for Blacks or Hispanics. DISCUSSION: Educational attainment does not contribute to CR similarly across racial/ethnic groups.

Progress and future challenges in aging and diversity research in the United States.

In 2016, the UC Davis Latino Aging Research Resource Center and UC Davis Alzheimer's Disease Center brought together experts from across the country to consolidate current knowledge and identify future directions in aging and diversity research. This report disseminates the research priorities that emerged from this conference, building on an earlier Gerontological Society of America preconference. We review key racial/ethnic differences in cognitive aging and dementia and identify current knowledge gaps in the field. We advocate for a systems-level framework for future research whereby environmental, sociocultural, behavioral, neuropathological, genetic, and psychometric levels of analysis are examined together to identify pathways and mechanisms that influence disparities. We then discuss steps to increase the recruitment and retention of racial/ethnic minorities in aging studies, as none of the recommendations will be possible without strong collaboration between racial/ethnic minority communities and researchers. This approach is consistent with the National Institute on Aging Health Disparities Research Framework.

18F-Fluorodeoxyglucose Positron Emission Tomography Cortical Metabolic Activity Associated with Distinct Agitation Behaviors in Alzheimer Disease.

OBJECTIVE: This study aimed to investigate the neurobiologic correlates of two distinct clusters of agitation symptoms to identify the unique biologic substrates underlying agitated behaviors. METHODS: Eighty-eight outpatients with mild to moderate Alzheimer disease (AD) were recruited from the VA Greater Los Angeles Healthcare System Geropsychiatry Outpatient Program. A cross-sectional investigation was conducted of the relationship between cerebral glucose metabolism measured via 18F-fluorodeoxyglucose positron emission tomography and agitated symptoms from the Neuropsychiatric Inventory (NPI) in patients with AD. Two empirically derived clusters of agitation symptoms were investigated: an Agitation factor comprising agitation/aggression and irritability/lability items of the NPI, and a Behavioral Dyscontrol factor comprising elation/euphoria, disinhibition, aberrant motor behavior, sleep, and appetite items of the NPI. Mean cerebral metabolism for patients who scored positively on each of the two factors was compared with mean cerebral metabolism for those who did not. RESULTS: Patients with AD who scored positively on the Agitation factor showed reduced glucose metabolism of the right temporal, right frontal, and bilateral cingulate cortex. In contrast, the Behavioral Dyscontrol factor did not show specific neurobiologic correlates. CONCLUSION: Symptoms encompassed within the Agitation factor have distinct neurobiologic underpinnings. The precipitants, course, and outcomes related to these symptoms may be unique from other neuropsychiatric symptoms characteristic of AD. Special attention to treatment of agitated behaviors involving anger, aggressiveness, hostility, and irritability/emotional lability is warranted, because they appear to reflect a clinically relevant symptom cluster with unique underlying neurobiologic correlates.

Cholinergic Receptor Binding in Alzheimer Disease and Healthy Aging: Assessment In Vivo with Positron Emission Tomography Imaging.

OBJECTIVE: To compare regional nicotinic cholinergic receptor binding in older adults with Alzheimer disease (AD) and healthy older adults in vivo and to assess relationships between receptor binding and clinical symptoms. METHODS: Using cross-sectional positron emission tomography (PET) neuroimaging and structured clinical assessment, outpatients with mild to moderate AD (N = 24) and healthy older adults without cognitive complaints (C group; N = 22) were studied. PET imaging of α4ß2* nicotinic cholinergic receptor binding using 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and clinical measures of global cognition, attention/processing speed, verbal memory, visuospatial memory, and neuropsychiatric symptoms were used. RESULTS: 2FA binding was lower in the AD group compared with the C group in the medial thalamus, medial temporal cortex, anterior cingulate, insula/opercula, inferior caudate, and brainstem (p < 0.05, corrected cluster), but binding was not associated with cognition. The C group had significant inverse correlations between 2FA binding in the thalamus (left: rs = -0.55, p = 0.008; right: rs = -0.50, p = 0.02; N = 22) and hippocampus (left: rs = -0.65, p = 0.001; right: rs = -0.55, p = 0.009; N = 22) and the Trails A score. The AD group had inverse correlation between 2FA binding in anterior cingulate (left: rs = -0.50, p = 0.01; right: rs = -0.50, p = 0.01; N = 24) and Neurobehavioral Rating Scale agitation/disinhibition factor score. CONCLUSION: Cholinergic receptor binding is reduced in specific brain regions in mild to moderate AD and is related to neuropsychiatric symptoms. Among healthy older adults, lower receptor binding may be associated with slower processing speed. Cholinergic receptor binding in vivo may reveal links to other key brain changes associated with aging and AD and may provide a potential molecular treatment target.

Neurobiology of delusions, memory, and insight in Alzheimer disease.

OBJECTIVE: Delusional thoughts are common among patients with Alzheimer disease (AD) and may be conceptually linked to memory deficits (cannot recall accurate information, which leads to inaccurate beliefs) and poor insight (unable to appreciate the illogic of beliefs). This study's goals were to examine the clinical associations among delusions, memory deficits, and poor insight; explore neurobiologic correlates for these symptoms; and identify shared mechanisms. METHODS: In a cross-sectional analysis, 88 outpatients with AD (mean Mini-Mental State Exam score: 19.3) were studied. Delusional thoughts were assessed with the Neuropsychiatric Inventory, level of inaccurate insight was assessed with the Neurobehavioral Rating Scale, and memory was assessed with the Mattis Dementia Rating Scale memory subscale. (18)F-fluorodeoxyglucose positron emission tomography was used to measure regional cortical metabolism. Relationships between clinical ratings and regional cortical metabolic activity (voxel-based) were assessed using SPM2. RESULTS: Patients with delusions had lower Dementia Rating Scale memory subscale scores. Neurobehavioral Rating Scale inaccurate insight scores were no different in those with and without delusions. Cortical metabolic activity was lower in the right lateral frontal cortex, orbitofrontal cortex, and bilateral temporal cortex in patients with delusions. Low cortical metabolic activity in the right lateral, inferior, and medial temporal cortex was associated with poorer memory. This region partially overlapped the region of hypometabolism associated with delusions. In contrast, low cortical metabolic activity in bilateral medial frontal cortex was associated with poor insight. CONCLUSION: Delusions in AD are associated with dysfunction in specific frontal and temporal cortical regions. Delusions are partially clinically and neurobiologically linked to memory deficits but not to poor insight.

Differences in anxiety among patients with early- versus late-onset Alzheimer's disease.

The authors sought to evaluate the incidence and correlates of anxiety in early-onset Alzheimer's disease (EOAD) versus the more typical late-onset AD (LOAD). A group of 23 EOAD and 22 LOAD patients were compared by the Neuropsychiatric Inventory Anxiety subscale. Demographic and disease-related relationships with anxiety were evaluated, as well as types of anxiety symptoms that were endorsed. EOAD patients had significantly more anxiety symptoms than LOAD patients. Among those with EOAD, anxiety was associated with male gender, higher Mini-Mental State Exam score, and separation from caregivers. Among LOAD patients, anxiety was associated with psychotic and activating psychiatric symptoms. These results have implications for the management and alleviation of anxiety in AD.

Insight in Alzheimer's disease and its relation to psychiatric and behavioral disturbances.

OBJECTIVE: Individuals suffering from Alzheimer's disease (AD) often have impaired awareness or a lack of insight into their cognitive deficits and functional abilities, especially in the later stages of the disease. Previous research has documented a relationship between depression and insight in AD, such that greater awareness of one's disease has been associated with a higher degree of depression. However, little is known about the relationship between insight, cognitive decline, and other psychiatric or behavioral problems associated with AD. METHODS: This study included 107 outpatients who met criteria for probable AD. Instruments included the Neurobehavioral Rating Scale, the Apathy Evaluation Scale, and the mini mental state exam. A series of hierarchical regression analyses were conducted to determine the relationship between insight and depressed mood, anxiety, psychosis, apathy, agitation, and behavioral retardation in AD patients after controlling for cognitive skills. RESULTS: Insight was found to significantly predict depressed mood, anxiety, and apathy even after controlling for global cognition. Greater insight was found to be associated with depressed mood and anxiety. However, impaired insight was associated with higher levels of apathy. CONCLUSION: Insight may be differentially related to mood symptoms and apathy within AD, such that patients with intact insight are more depressed, whereas patients with impaired insight are more apathetic. This suggests that assessment of insight in AD may complement the clinical evaluation of depression and apathy in AD and help guide the most appropriate interventions. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Emotional Awareness and Expression Therapy vs Cognitive Behavioral Therapy for Chronic Pain in Older Veterans: A Randomized Clinical Trial.

Importance: Chronic pain is common and disabling in older adults, and psychological interventions are indicated. However, the gold standard approach, cognitive-behavioral therapy (CBT), produces only modest benefits, and more powerful options are needed. Objectives: To evaluate whether emotional awareness and expression therapy (EAET) is superior to CBT for treatment of chronic pain among predominantly male older veterans and whether higher baseline depression, anxiety, or posttraumatic stress disorder (PTSD) symptoms-key targets of EAET-moderate treatment response. Design, Setting, and Participants: This 2-arm randomized clinical trial was conducted from May 16, 2019, to September 14, 2023, in the US Department of Veterans Affairs Greater Los Angeles Healthcare System. The trial included a racially and ethnically diverse group of veterans aged 60 to 95 years with at least 3 months of musculoskeletal pain. Interventions: Emotional awareness and expression therapy or CBT, conducted concurrently, each presented as one 90-minute individual session followed by eight 90-minute group sessions. Main Outcomes and Measures: The primary outcome was Brief Pain Inventory pain severity (range, 0 to 10) from baseline to posttreatment (week 10, primary end point) and 6-month follow-up. Secondary outcomes included Patient Reported Outcomes Institute Measurement System Anxiety, Depression, Fatigue, General Life Satisfaction (NIH Toolbox), Pain Interference, and Sleep Disturbance Short Forms, Patient Global Impression of Change (PGIC), and Satisfaction with Therapy and Therapist Scale-Revised. A subset of participants completed the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). All analyses were for the intention-to-treat population and included all randomized participants. Results: Among 126 randomized participants (66 in the EAET group and 60 in the CBT group; mean [SD] age, 71.9 [5.9] years; 116 [92%] male), 111 (88%) completed posttreatment, and 104 (82%) completed the 6-month follow-up. The EAET was superior to CBT for the primary outcome of reduction in pain severity at posttreatment (estimate, -1.59 [95% CI, -2.35 to -0.83]; P < .001) and follow-up (estimate, -1.01 [95% CI, -1.78 to -0.24]; P = .01). A greater percentage of participants in EAET vs CBT had clinically significant (at least 30%) pain reduction (63% vs 17%; odds ratio, 21.54 [95% CI, 4.66-99.56]; P < .001) at posttreatment. In addition, EAET was superior to CBT on 50% pain reduction (35% vs 7%; odds ratio, 11.77 [95% CI, 2.38-58.25]; P = .002), anxiety (estimate, -2.49 [95% CI, -4.30 to -0.68]; P = .006), depression (estimate, -3.06 [95% CI, -5.88 to -0.25]; P = .03), general life satisfaction (estimate, 1.23 [95% CI, 0.36-2.10]; P = .005), PTSD symptoms (estimate, -4.39 [95% CI, -8.44 to -0.34]; P = .03), PGIC score (estimate, 1.46 [95% CI, 0.77-2.15]; P < .001), and global treatment satisfaction (estimate, 0.28 [95% CI, 0.12-0.45]; P < .001) at posttreatment. Higher baseline depression (estimate, -1.55 [95% CI, -0.37 to 2.73]; P < .001), anxiety (estimate, -1.53 [95% CI, -2.19 to -0.88]; P < .001), and PTSD symptoms (estimate, -1.69 [95% CI, -2.96 to -0.42]; P = .009) moderated greater reduction in pain severity after EAET but not CBT. Conclusions and Relevance: The results of this randomized clinical trial suggest that EAET may be a preferred intervention for medically and psychiatrically complex patients with pain. The societal burden of chronic pain could be improved by further incorporating the principles of EAET into mainstream clinical pain medicine. Trial Registration: ClinicalTrials.gov Identifier: NCT03918642.

A Transdisciplinary Program for Care of Veterans With Neurocognitive Disorders.

Background: Veterans face specific risk factors for neurocognitive disorders. Providing them with comprehensive care for dementia and related neurocognitive disorders is a challenge as the population ages. There is a need for family-centered interventions, specialized expertise, and collaboration among clinicians and caregivers. The literature suggests that application of a transdisciplinary care model can address these needs and provide effective dementia care. Observations: The Veterans Affairs Greater Los Angeles Healthcare System has employed existing expertise to create a conference-centered transdisciplinary model that responds to the US Department of Veterans Affairs directive for a dementia system of care. This model involves direct participation of behavioral neurology, geriatric psychiatry, geriatrics, neuropsychology, nursing, and social work. In this model, the social worker serves as a dementia care manager and, along with the nurse specialist, assures long-term management through follow-up and monitoring. Transdisciplinary interactions occur in a clinical case conference where each discipline contributes to the veteran's care. The team generates a final report on treating these veterans, the caregiver's needs, referral for psychosocial services, and plans for monitoring and follow-up. Conclusions: This model could be a template of a program for implementing the Dementia System of Care across Veteran Affairs medical centers.

Correlates of functional status among OEF/OIF veterans with a history of traumatic brain injury.

This study was conducted to identify factors related to functional status within a clinical sample of Veterans of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) with a history of traumatic brain injury (TBI). Medical chart review was conducted for a consecutive group of OEF/OIF Veterans who were referred for neuropsychological evaluation within a Veterans Affairs Medical Center Polytrauma Program related to history of TBI (n = 57). Level of involvement in occupational and academic activity, presence or absence of housing insecurity, and clinician ratings of overall functioning served as indicators of functional status. Reduced functional status was most strongly related to poorer cognitive function, particularly motor function, processing speed, and executive function. Lower levels of functioning were also related to increased severity of postconcussive symptoms, lower levels of education, and ongoing medication treatment for sleep or psychiatric symptoms. Comprehensive evaluation of cognitive, affective, and behavioral functioning among OEF/OIF Veterans with a history of TBI is likely to provide valuable information to inform rehabilitation strategies and identify potential warning signs for poor postdeployment reintegration. Increased awareness of these factors may aid clinicians in identifying patients at risk for poor outcomes and in more effectively targeting symptoms for intervention.

Cholinergic receptor binding in unimpaired older adults, mild cognitive impairment, and Alzheimer's disease dementia.

BACKGROUND: Cholinergic neurotransmitter system dysfunction contributes to cognitive impairment in Alzheimer's disease and other syndromes. However, the specific cholinergic mechanisms and brain structures involved, time course of alterations, and relationships with specific cognitive deficits are not well understood. METHODS: This study included 102 older adults: 42 cognitively unimpaired (CU), 28 with mild cognitive impairment (MCI), and 32 with Alzheimer's disease (AD) dementia. Each participant underwent a neuropsychological assessment. Regional brain α4ß2 nicotinic cholinergic receptor binding (VT/fp) was measured using 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2FA) and PET imaging. Voxel-wise analyses of group differences were performed. Relationships between receptor binding and cognition, age, and cholinesterase inhibitor medication use were assessed using binding values in six prespecified regions of interest. RESULTS: SPM analysis showed the group VT/fp binding differences in the bilateral entorhinal cortex, hippocampus, insula, anterior cingulate, thalamus, and basal ganglia (p < .05, FWE-corrected). Pairwise comparisons revealed lower binding in the AD group compared to the CU group in similar regions. Binding in the entorhinal cortex was lower in the MCI group than in the CU group; binding in the hippocampus was lower in the AD group than in the MCI group. AD participants taking cholinesterase inhibitor medication had lower 2FA binding in the bilateral hippocampus and thalamus compared to those not taking medication. In the CU group, age was negatively associated with 2FA binding in each region of interest (rs = - .33 to - .59, p < .05 for each, uncorrected). Attention, immediate recall, and delayed recall scores were inversely associated with 2FA binding in most regions across the full sample. In the combined group of CU and MCI participants, attention was inversely associated with 2FA binding in most regions, beyond the effect of hippocampal volume. CONCLUSIONS: Nicotinic cholinergic receptor binding in specific limbic and subcortical regions is lower in MCI and further reduced in AD dementia, compared to CU older adults, and is related to cognitive deficits. Cognitive decline with age may be a consequence of reduced cholinergic receptor density or binding affinity that may also promote vulnerability to other Alzheimer's processes. Contemporary modification of the "cholinergic deficit" of aging and AD may reveal opportunities to prevent or improve clinical symptoms.

Pathophysiology of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia worldwide. While neuritic plaques consisting of aggregated amyloid-beta proteins and neurofibrillary tangles of accumulated tau proteins represent the pathophysiologic hallmarks of AD, numerous processes likely interact with risk and protective factors and one's culture to produce the cognitive loss, neuropsychiatric symptoms, and functional impairments that characterize AD dementia. Recent biomarker and neuroimaging research has revealed how the pathophysiology of AD may lead to symptoms, and as the pathophysiology of AD gains clarity, more potential treatments are emerging that aim to modify the disease and relieve its burden.

Increasing depressive symptoms in children of Alzheimer parents.

Children of persons with Alzheimer disease (AD) are at increased risk of developing AD themselves, but specific factors that predict AD in this population have yet to be elucidated. Various studies indicate depressive symptoms may predate clinical AD and represent a risk factor and/or prodrome of incipient dementia, but their relevance for AD offspring remains uncertain. As part of a longitudinal family study of AD, we assessed depressive symptomatology in 30 middle aged AD offspring (mean age at baseline: 41.2). Their mean total scores on the Hamilton Depression Rating scale increased from 1.8 to 5.3 (P < .001) across a 20-year interval. Neurocognitive performance remained stable in a subset of this cohort (N = 25) over the same interval. Findings from this small convenience sample suggest emerging depressive symptoms may be among the earliest signs of subsequent dementia in this high-risk population but require confirmation through further longitudinal follow-up and replication in larger populations.

Cerebral metabolism, cognition, and functional abilities in Alzheimer disease.

Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD.

PTSD Improvement Associated with Social Connectedness in Gerofit Veterans Exercise Program.

OBJECTIVE: Post-traumatic stress disorder (PTSD) is common in Veterans. Symptoms can perpetuate into late life, negatively impacting physical and mental health. Exercise and social support are beneficial in treating anxiety disorders such as PTSD in the general population, although less is known about the impact on Veterans who have lived with PTSD for decades. This study assessed associations between social connectedness, physical function and self-reported change in PTSD symptoms among older Veterans specifically participating in Gerofit. DESIGN: Prospective clinical intervention. SETTING: Twelve sites of Veterans Affairs (VA) Gerofit exercise program across the United States. PARTICIPANTS: Three hundred and twenty one older Veteran Gerofit participants (mean age = 74) completed physical assessments and questionnaires regarding physical and emotional symptoms and their experience. MEASUREMENTS: Measures of physical function, including 30-second chair stands, 10-m and 6-min walk were assessed at baseline and 3 months; change in PTSD symptoms based on the Diagnostic Statistical Manual-5 (DSM-5) assessed by a self-report questionnaire; and social connection measured by the Relatedness Subscale of the Psychological Need Satisfaction in Exercise scale (PNSE) were evaluated after 3 months of participation in Gerofit. RESULTS: Ninety five (29.6%) Veterans reported PTSD. Significant improvement was noted in self-rated PTSD symptoms at 3 months (P < .05). Moderate correlation (r = .44) was found between social connectedness with other participants in Gerofit and PTSD symptom improvement for those Veterans who endorsed improvement (n = 59). All participants improved on measures of physical function. In Veterans who endorsed PTSD there were no significant associations between physical function improvement and PTSD symptoms. CONCLUSION: Veterans with PTSD that participated in Gerofit group exercise reported symptom improvement, and social connectedness was significantly associated with this improvement. In addition to physical health benefits, the social context of Gerofit may offer a potential resource for improving PTSD symptoms in older Veterans that warrants further study.

Effect of memantine treatment on regional cortical metabolism in Alzheimer's disease.

OBJECTIVES: Cortical systems involved in the response to medication treatment for Alzheimer's disease (AD) are poorly understood. Preclinical studies have demonstrated the effect of memantine on neuroreceptors and cell physiology, although the impact of treatment on cortical activity in vivo is not known. DESIGN: F-fluorodeoxyglucose positron emission tomography (PET) imaging and clinical assessment before and after open-label memantine treatment. PARTICIPANTS/SETTING: Seventeen outpatients with probable AD on stable cholinesterase inhibitor medication. INTERVENTION: Memantine up to 10 mg twice daily for 10 weeks. MEASUREMENTS: Voxel-based analyses of change in cortical metabolic activity; Mattis Dementia Rating Scale (DRS), and Neurobehavioral Rating Scale (NRS). RESULTS: : Mean age was 81 years; mean Mini-Mental State Examination score was 19.4. Compared with baseline, metabolic activity was significantly higher after 10 weeks memantine treatment in two cortical regions bilaterally: the inferior temporal gyrus (BA 20) and the angular gyrus/supramarginal gyrus (BA 39, 40). There was no significant relationship between change in DRS score and change in cortical metabolism, although change in NRS score was associated with the extent of metabolic change in the right parietal and temporal cortex. CONCLUSION: Metabolic activity in bilateral inferior parietal and temporal cortex increases during 10 weeks of memantine treatment in patients with AD. PET imaging can reveal functional effects of medications on neural activity and may help to define critical mechanisms involved in drug treatment.

Executive deficits and regional brain metabolism in Alzheimer's disease.

OBJECTIVE: Executive deficits are common in patients with Alzheimer's disease (AD), contribute prominently to clinical disability, and may be associated with frontal lobe pathology. This study examined regional brain hypometabolism associated with executive dysfunction in patients with AD. METHODS: Forty-one patients with probable AD underwent [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at rest. Neuropsychological measures of executive control included the Conceptualization (Conc) and Initiation/Perseveration (I/P) subscales of the Mattis Dementia Rating Scale (DRS), the Wechsler Adult Intelligence Scale (WAIS) Similarities subtest, the Tower test, and the Ruff Figural Fluency test (Ruff). Voxel-based analyses were conducted using statistical parametric mapping (SPM2) to measure the correlation between regional cerebral metabolism and executive measures. Correlations independent of global cognitive impairment were identified by including Mini-Mental State Examination (MMSE) score as a covariate in the model. RESULTS: Executive deficits, as measured by poor performances on the DRS I/P and Conc subscales, were associated with hypometabolism in the bilateral mid-dorsolateral frontal region. Activity in posterior cortical regions also contributed uniquely to some aspects of executive functioning, as lower resting metabolism in parietal or temporal cortex was correlated with poor performance on four of the five executive measures. After controlling for global cognitive score, there were significant extra-frontal correlations with hypometabolism in insula, occipital lobe, and temporal cortex. CONCLUSIONS: Some but not all executive deficits in AD are associated with neural activity in the dorsolateral frontal cortex. Activities in distributed neural systems that include parietal and temporal cortex also contribute to some executive abilities. The pathophysiology of executive dysfunction is complex and includes abnormalities not limited to a single region.