Enhancing Brain Health and Well-Being in Older Adults: Innovations in Lifestyle Interventions.

PURPOSE OF REVIEW: This article will provide clinicians with guidance on helping older adult patients make lifestyle changes to enhance brain health and well-being. RECENT FINDINGS: Evidence suggests that physical activity might be helpful in improving cognitive functioning. The data on the benefits of cognitive activity is inconsistent and not as robust. The MediDiet, DASH, and MIND diets have been associated with better cognitive health. Sleep hygiene and cognitive behavioral therapies are considered first line evidence-based treatments for insomnia and the maintenance of healthy sleep patterns. Mindfulness based interventions have been shown to reduce anxiety, depression, and stress, and can help some older adults manage pain more constructively. Evidence-based information regarding the four topics of exercise, nutrition, sleep, and mindfulness is reviewed, so that clinicians may be better able to optimize care for their older adult patients.

Residual stress and osmotic swelling of the periodontal ligament.

Osmotic swelling and residual stress are increasingly recognized as important factors in soft tissue biomechanics. Little attention has been given to residual stress in periodontal ligament (PDL) biomechanics despite its rapid growth and remodeling potential. Those tissues that bear compressive loads, e.g., articular cartilage, intervertebral disk, have received much attention related to their capacities for osmotic swelling. To understand residual stress and osmotic swelling in the PDL, it must be asked (1) to what extent, if any, does the PDL exhibit residual stress and osmotic swelling, and (2) if so, whether residual stress and osmotic swelling are mechanically significant to the PDL's stress/strain behavior under external loading. Here, we incrementally built a series of computer models that were fit to uniaxial loading, osmotic swelling and residual stretch data. The models were validated with in vitro shear tests and in vivo tooth-tipping data. Residual stress and osmotic swelling models were used to analyze tension and compression stress (principal stress) effects in PDL specimens under external loads. Shear-to-failure experiments under osmotic conditions were performed and modeled to determine differences in mechanics and failure of swollen periodontal ligament. Significantly higher failure shear stresses in swollen PDL suggested that osmotic swelling reduced tension and thus had a strengthening effect. The in vivo model's first and third principal stresses were both higher with residual stress and osmotic swelling, but smooth stress gradients prevailed throughout the three-dimensional PDL anatomy. The addition of PDL stresses from residual stress and osmotic swelling represents a unique concept in dental biomechanics.

Buccal alveolar bone changes following rapid maxillary expansion and fixed appliance therapy.

OBJECTIVES: To assess factors that may be associated with buccal bone changes adjacent to maxillary first molars after rapid maxillary expansion (RME) and fixed appliance therapy. MATERIALS AND METHODS: Pretreatment (T1) and posttreatment (T2) cone-beam computed tomography scans were obtained from 45 patients treated with RME and preadjusted edgewise appliances. Buccal alveolar bone thickness was measured adjacent to the mesiobuccal root of the maxillary first molar 4 mm, 6 mm, and 8 mm apical to the cementoenamel junction, and anatomic defects were recorded. Paired and unpaired t-tests were used to compare alveolar bone thickness at T1 and T2 and to determine whether teeth with posttreatment anatomic defects had thinner initial bone. Correlation analyses were used to examine relationships between buccal alveolar bone thickness changes and amount of expansion, initial bone thickness, age at T1, postexpansion retention time, and treatment time. RESULTS: There was a statistically significant reduction in buccal alveolar bone thickness from T1 to T2. Approximately half (47.7%) of the teeth developed anatomic defects from T1 to T2. These teeth had significantly thinner buccal bone at T1. Reduction in alveolar bone thickness was correlated with only one tested variable: initial bone thickness. CONCLUSIONS: RME and fixed-appliance therapy can be associated with significant reduction in buccal alveolar bone thickness and an increase in anatomic defects adjacent to the expander anchor teeth. Anchor teeth with greater initial buccal bone thickness have less reduction in buccal bone thickness and are less likely to develop posttreatment anatomic defects of buccal bone.

Resistance to sliding of orthodontic archwires under increasing applied moments.

BACKGROUND: Orthodontic treatment with fixed appliances involves sliding of brackets along archwires. These movements involve friction, which causes resistance to sliding. In addition, moments cause teeth to tip until binding occurs between the bracket and archwire. The manufacturer of a new TiMolium®Titanium archwire claims material properties superior to ß-Titanium, potentially leading to reduced resistance to sliding. OBJECTIVE: To compare TiMolium archwires with ß-Titanium and stainless steel archwires as the current gold standard for sliding mechanics under application of an increasing moment. MATERIALS AND METHODS: A total of 120 stainless steel (Smartclip, 3M, Monrovia, CA) and ceramic self-ligating 0.022″-slot brackets (Clarity SL, 3M) were divided into six equal-sized groups. Resistance to sliding was tested with 0.019″ × 0.025″ TiMolium (TP Orthodontics, La Porte, IN), ß-Titanium (3M), and stainless steel (3M) archwires using a custom-designed apparatus to simulate sliding mechanics and application of moments of 1000, 2000, and 3000 g-mm. RESULTS: Using stainless steel brackets, the TiMolium archwires had significantly higher resistance to sliding than stainless steel archwires at all moments tested while there was no difference between TiMolium and ß-Titanium. Using ceramic brackets, the resistance to sliding with TiMolium archwires was no different than with stainless steel archwires. Both TiMolium and stainless steel archwires showed significantly lower resistance to sliding than ß-Titanium. CONCLUSION: TiMolium archwires have resistance to sliding intermediary to stainless steel and ß-Titanium archwires when clinically relevant moments are applied. Used with the stainless steel brackets, they behave like ß-Titanium, whereas used with the ceramic brackets, they behave more like stainless steel.

GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

(Reprinted with permission from Am J Psychiatry 2017; 174:1086-1093).

The Use of Antidepressants in Bipolar Depression.

Depression remains a significant debilitating and frequent phase of illness for patients with bipolar disorder. There are few FDA-approved medications for its treatment, only one of which includes a traditional antidepressant (olanzapine-fluoxetine combination), despite studies that demonstrate traditional antidepressants are one of the most commonly prescribed class of medications for bipolar patients in a depressive episode. While traditional antidepressants remain the primary option for treatment of unipolar depression, their use in bipolar depression has been controversial due to a limited efficacy evidence and the concern for potential harm. This chapter reviews the current data concerning the use of traditional antidepressants in bipolar disorder, and the current expert treatment guideline recommendations for their use.

Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial.

OBJECTIVE: Depression and cognitive impairment are often comorbid in older adults, but optimal treatment strategies remain unclear. In a two-site study, the efficacy and safety of add-on donepezil versus placebo were compared in depressed patients with cognitive impairment receiving stable antidepressant treatment. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in older adults with depression and cognitive impairment (https://clinicaltrials.gov/ct2/show/NCT01658228; NCT01658228). Patients received open-label antidepressant treatment for 16 weeks, initially with citalopram and then with venlafaxine, if needed, followed by random assignment to add-on donepezil 5-10 mg daily or placebo for another 62 weeks. Outcome measures were neuropsychological test performance (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog] and Selective Reminding Test [SRT] total immediate recall) and instrumental activities of daily living (Functional Activities Questionnaire). RESULTS: Of 81 patients who signed informed consent, 79 patients completed the baseline evaluation. Open antidepressant treatment was associated with improvement in depression in 63.93% responders by week 16. In the randomized trial, there were no treatment group differences between donepezil and placebo on dementia conversion rates, ADAS-Cog, SRT total immediate recall, or FAQ. Neither baseline cognitive impairment severity nor apolipoprotein E e4 genotype influenced donepezil efficacy. Donepezil was associated with more adverse effects than placebo. CONCLUSION: The results do not support adjunctive off-label cholinesterase inhibitor treatment in patients with depression and cognitive impairment. The findings highlight the need to prioritize discovery of novel treatments for this highly prevalent population with comorbid illnesses.

Predictors of recurrence in remitted late-life depression.

BACKGROUND: Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD. METHODS: Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI). RESULTS: Of 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence. CONCLUSIONS: Over half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk.

Advances in Pharmacotherapy of Late-Life Depression.

This paper reviews recent research on late-life depression (LLD) pharmacotherapy, focusing on updated information for monotherapy and augmentation treatments. We then review new research on moderators of clinical response and how to use the information for improved efficacy. RECENT FINDINGS: A recent review shows that sertraline, paroxetine, and duloxetine were superior to placebo for the treatment of LLD. There is concern that paroxetine could have adverse outcomes in the geriatric population due to anticholinergic properties; however, studies show no increases in mortality, dementia risk, or cognitive measures. Among newer antidepressants, vortioxetine has demonstrated efficacy in LLD, quetiapine has demonstrated efficacy especially for patients with sleep disturbances, and aripiprazole augmentation for treatment resistance in LLD was found to be safe and effective. Researchers have also been identifying moderators of LLD that can guide treatment. Researchers are learning how to associate moderators, neuroanatomical models, and antidepressant response. SSRI/SNRIs remain first-line treatment for LLD. Aripiprazole is an effective and safe augmentation for treatment resistance. Studies are identifying actionable moderators that can increase treatment response.

GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

OBJECTIVE: Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific randomized controlled trials. The authors describe findings from a first such study of late-life mania. METHOD: The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. Participants were randomly assigned, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80-0.99 mEq/L) or divalproex (target serum valproate concentration, 80-99 µg/mL) for 9 weeks. Participants with an inadequate response after 3 weeks received open adjunctive risperidone. The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium. Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations. Efficacy was assessed with the Young Mania Rating Scale (YMRS). RESULTS: Attrition rates were similar for lithium and divalproex (14% and 18% at week 3 and 51% and 44% at week 9, respectively). The groups did not differ significantly in sedation. Participants in the lithium group tended to experience more tremor. Similar proportions of participants in the lithium and divalproex groups achieved target concentrations (57% and 56%, respectively). A longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09). Nine-week response rates did not differ significantly between the lithium and divalproex groups (79% and 73%, respectively). The need for adjunctive risperidone was low and similar between groups (17% and 14%, respectively). CONCLUSIONS: Both lithium and divalproex were adequately tolerated and efficacious; lithium was associated with a greater reduction in mania scores over 9 weeks.

Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression.

OBJECTIVE: Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. METHODS: In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. RESULTS: Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. CONCLUSION: Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.

Effects of stressful life events on cerebral white matter hyperintensity progression.

OBJECTIVE: Exposure to stressful events is associated with both occurrence of depression and also vascular disease. The objective of this study was to determine whether higher levels of stress exposure was related to measures of pathological brain aging, specifically white matter hyperintensity volumes, in older adults with and without depression. METHODS: The sample included 130 depressed and 110 never-depressed older adults aged 60 years or older enrolled in a longitudinal study at an academic medical center. Participants completed clinical assessments, assessment of stressful event exposure and perceived stress, and magnetic resonance imaging at baseline and after 2 years. Analyses examined both cross-sectional and longitudinal relationships between stress measures and white matter hyperintensity volumes. RESULTS: There were no statistically significant relationships observed between cross-sectional baseline stress measures and either baseline hyperintensity volume or 2-year change in hyperintensity volume. However, after controlling for demographic variables and baseline measures, change in stressor exposure was associated with change in hyperintensity volumes. In this analysis, increased stressor exposure was associated with greater increases in white matter hyperintensity volume, while reductions in stressor exposure were associated with less increase in hyperintensity volume. This relationship did not significantly differ based on the presence of either depression or medical comorbidities. CONCLUSIONS: This work adds to a growing literature associating exposure to stressful events in later life with more rapid pathological brain aging. Work is needed to understand the physiological mechanisms by which stress exposure has this effect and examine whether stress reduction techniques may modify these observed outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Adjunctive brexpiprazole for the treatment of major depressive disorder.

INTRODUCTION: The lifetime prevalence of major depressive episodes in the United States is nearly 17%. Clinical trials and clinical effectiveness studies have demonstrated that many patients will fail to achieve remission using traditional monotherapy, contributing to significant morbidity and suffering. Because of this, augmentation strategies have been proposed to improve both treatment response and remission. Areas covered: Brexpiprazole is a second generation antipsychotic (SGA) approved by the US FDA in 2015 as an add-on treatment to an antidepressant medication for the treatment of adults with MDD, based on the results of two large-scale, randomized, placebo-controlled trials. It is thought to exert its antidepressant effect by a partial agonism of both the dopamine D2 and serotonin 5HT1A receptors. In addition, it also has potent antagonistic activity at 5HT2A, α1B and α2 C receptors, which may also contribute to monoamine transmission regulation. Expert Opinion: Overall, the tolerability of brexpiprazole is promising with relatively low rates of side effects and discontinuation rates, thus establishing it as a new option for the treatment of depression.

Nutrition and Bipolar Depression.

As with physical conditions, bipolar disorder is likely to be impacted by diet and nutrition. Patients with bipolar disorder have been noted to have relatively unhealthy diets, which may in part be the reason they also have an elevated risk of metabolic syndrome and obesity. An improvement in the quality of the diet should improve a bipolar patient's overall health risk profile, but it may also improve their psychiatric outcomes. New insights into biological dysfunctions that may be present in bipolar disorder have presented new theoretic frameworks for understanding the relationship between diet and bipolar disorder.

Suicide Behaviors in Bipolar Disorder: A Review and Update for the Clinician.

Suicide behaviors (ideation, attempts, and completions) are unfortunately common in patients with bipolar disorder. It is estimated that 25 to 50% attempt suicide at least once during their lifetime, and 6% to 19% complete suicide. Risk factors include a family history of suicide, previous suicide attempts, younger age of onset, comorbid psychiatric illnesses, and psychological constructs like hopelessness. Pharmacologic treatment may impact suicidal behaviors, either increasing vulnerability or resilience. Clinicians need to be particularly sensitive to their patient's thoughts and beliefs about death, particularly during stressful times of life or when in a depressive/mixed episode of bipolar disorder.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force.

OBJECTIVES: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). METHODS: This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. RESULTS: The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. CONCLUSIONS: Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan.

Social support in late life mania: GERI-BD.

OBJECTIVE: Using the database of the National Institute of Mental Health-sponsored acute treatment of late life mania study (GERI-BD), we assessed the role of social support in the presentation of late life bipolar mania. METHODS: In the first 100 subjects randomized in geriatric BD, we explored the demographic, clinical, and social support characteristics (assessed using the Duke Social Support Index) and aspects of manic presentation. We selected two dependent variables: symptom severity, as determined by the Young Mania Rating Scale (YMRS) at baseline, and duration of episode. We selected nine potential independent variables on the basis of Pearson correlation coefficients. We derived two final models using multiple regression analysis employing an iterative process. RESULTS: In our severity model, being married was associated with a higher YMRS score (p = 0.05), whereas higher social interaction scores with non-family members were associated with a lower YMRS score (p = 0.011). In the episode duration model, longer duration was associated with a higher Hamilton Depression Rating Scale score (p = 0.03) and higher social interaction scores with non-family members (p = 0.0003), younger age (p = 0.04), higher number of persons in one's family social network (p = 0.017), and higher instrumental support scores (p = 0.0062). CONCLUSIONS: In late life mania, more social interaction with one's community appears to be associated with less severe symptoms at presentation for treatment, however, it can also be associated with slightly longer the duration of episode. Two aspects of the Duke Social Support Index are associated with a shorter episode duration prior to seeking treatment: being part of a larger family network and a having a higher level of instrumental support prior to treatment. The Instrumental Support Subscale measures the degree of assistance that is available for the respondent in performing daily tasks. These findings suggest that in older adults with BD, close social interactions and support are important in limiting the length of the illness episode prior to treatment. Social interactions involving non-family members may be less important in moderating the intensity of the symptoms at presentation.

Effect of applied moment on resistance to sliding among esthetic self-ligating brackets.

OBJECTIVE: To determine the effect of mode of ligation and bracket material on resistance to sliding (RS) by comparing various esthetic brackets of conventionally ligated and self-ligating (SL) designs under an increasing applied moment in the second-order dimension. MATERIALS AND METHODS: Eight different commercially available esthetic brackets of SL and conventional elastomeric-ligated (CL) designs were mounted on a testing apparatus to simulate canine retraction using sliding mechanics and the application of a moment on 0.019″×0.025″ stainless steel archwire. The samples examined were the CL brackets Clarity™, Inspire Ice™, SpiritMB™, and Mystique™, and the SL brackets ClaritySL™, In-OvationC™, In-OvationR™, and Smartclip™. The RS at calculated moments of 2000 g-mm and 4000 g-mm was determined and compared between the various brackets. Descriptive measures and one-way analysis of variance were used to calculate means and statistical differences among the bracket types. RESULTS: The CL monocrystalline bracket displayed significantly greater (P < .05) RS than all other brackets tested. Among the other brackets, the range of RS values was 145.8-191.7 g and 291.9-389.2 g at moments of 2000 g-mm and 4000 g-mm, respectfully, though these differences were not significant (P < .05). All brackets tested displayed greater levels of RS (P < .05) at 4000 g-mm than at 2000 g-mm. CONCLUSION: With the exception of the CL monocrystalline bracket, all brackets displayed comparable amounts of RS regardless of mode of ligation or bracket slot material.