Depression is highly common throughout the life course and dementia is common in late life. The literature suggests an association between depression and dementia, and growing evidence implies that timing of depression may be important to defining the nature of the association. In particular, earlier-life depression or depressive symptoms consistently have been shown to be associated with a 2-fold or greater increase in risk of dementia. In contrast, studies of late-life depression have been more conflicting but the majority support an association; yet, the nature of this association is unclear (e.g., if depression is a prodrome or consequence or risk factor for dementia). The likely biological mechanisms linking depression to dementia include vascular disease, alterations in glucocorticoid steroids and hippocampal atrophy, increased deposition of β-amyloid plaques, inflammatory changes, and deficits of nerve growth factors. Treatment strategies for depression might intervene on these pathways and in turn may alter risk for dementia. Given the projected increase of dementia in the coming decades, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize and analyze current evidence for late-life and earlier-life depression and their relationship to dementia, discuss the primary underlying mechanisms and implications for treatment.

A home-based program targeting underlying impairments in physical abilities can reduce the progression of functional decline among physically frail, elderly persons who live at home.

Context Little is known about prevalence rates of DSM-IV disorders across age strata of older adults, including common conditions such as individual and coexisting mood and anxiety disorders. Objective To determine nationally representative estimates of 12-month prevalence rates of mood, anxiety, and comorbid mood-anxiety disorder across young-old, mid-old, old-old, and oldest old community-dwelling adults. Design and Setting The National Comorbidity Survey Replication (NCS-R) is a population-based probability sample of 9282 participants 18 years and older, conducted between February 2001 and April 2003. The NCS-R survey used the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants We studied the 2575 participants 55 years and older who were part of NCS-R (43% 55-64; 32% 65-74; 20% 75-84; 5% ≥85 years). This included only non-institutionalized adults, as all NCS-R participants resided in households within the community. Main Outcome Measures Twelve-month prevalence of mood disorders (MDD, dysthymia, bipolar disorder), anxiety disorders (panic disorder, agoraphobia, specific phobia, social phobia, generalized anxiety disorder, posttraumatic stress disorder), and coexisting mood-anxiety disorder were assessed using DSM-IV criteria. Prevalence rates were weighted to adjust for the complex design in order to infer generalizability to the U.S. population. Results The likelihood of having a mood, anxiety, or combined mood-anxiety disorder generally showed a pattern of decline with age (P < .05). Twelve-month disorders showed higher rates in women compared to men; a statistically significant trend with age. In addition, anxiety disorders were as high if not higher than mood disorders across age groups (overall 12-month rates: mood=5% and anxiety=12%). No differences were found between race/ethnicity groups. Conclusions Prevalence rates of DSM-IV mood and anxiety disorders in late life tend to decline with age, but remain very common; especially in women. These results highlight the need for intervention and prevention strategies.

Objectives: Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans.Methods: We performed a retrospective cohort study of 188,764 US veterans aged 55 years or older who had at least one inpatient or outpatient visit during both the baseline (2000)(2001)(2002)(2003) and follow-up (2003-2012) periods and did not have a dementia diagnosis at baseline. TBI and dementia diagnoses were determined using ICD-9 codes in electronic medical records. Fine-Gray proportional hazards models were used to determine whether TBI was associated with greater risk of incident dementia, accounting for the competing risk of death and adjusting for demographics, medical comorbidities, and psychiatric disorders.Results: Veterans were a mean age of 68 years at baseline. During the 9-year follow-up period, 16% of those with TBI developed dementia compared with 10% of those without TBI (adjusted hazard ratio, 1.57; 95% confidence interval: 1.35-1.83). There was evidence of an additive association between TBI and other conditions on risk of dementia.Conclusions: TBI in older veterans was associated with a 60% increase in the risk of developing dementia over 9 years after accounting for competing risks and potential confounders. Our results suggest that TBI in older veterans may predispose toward development of symptomatic dementia and raise concern about the potential long-term consequences of TBI in younger veterans and civilians. There is growing evidence that traumatic brain injury (TBI) is associated with a variety of shortand long-term adverse health outcomes. A 2008 Institute of Medicine report concluded that TBIs are consistently associated with an increased risk of unprovoked seizures, premature mortality, and neurocognitive deficits in the affected region, with evidence strongest for penetrating wounds and severe or moderate TBIs.1 However, prior research on the relationship between TBI and risk of Alzheimer disease (AD) and all-cause dementia has been mixed. [2][3][4][5][6][7][8][9][10][11][12][13][14] Most prior studies have not adequately controlled for potential confounders, such as medical and psychiatric comorbidities, and none have considered death as a competing risk.Furthermore, to our knowledge, only one prior study has specifically focused on examining the relationship between TBI and risk of dementia in veterans.11 Many veterans have other combatrelated risk factors such as posttraumatic stress disorder (PTSD) and depression, which have been associated with an increased risk of dementia in veterans in prior studies, 15,16 and could act as either confounders or effect modifiers of the association between TBI and dementia in veterans.

IMPORTANCE Traumatic brain injury (TBI) is common in both veteran and civilian populations. Prior studies have linked moderate and severe TBI with increased dementia risk, but the association between dementia and mild TBI, particularly mild TBI without loss of consciousness (LOC), remains unclear. OBJECTIVE To examine the association between TBI severity, LOC, and dementia diagnosis in veterans. DESIGN, SETTING, AND PARTICIPANTS This cohort study of all patients diagnosed with a TBI in the Veterans Health Administration health care system from October 1, 2001, to September 30, 2014, and a propensity-matched comparison group. Patients with dementia at baseline were excluded. Researchers identified TBIs through the Comprehensive TBI Evaluation database, which is restricted to Iraq and Afghanistan veterans, and the National Patient Care Database, which includes veterans of all eras. The severity of each TBI was based on the most severe injury recorded and classified as mild without LOC, mild with LOC, mild with LOC status unknown, or moderate or severe using Department of Defense or Defense and Veterans Brain Injury Center criteria. International Classification of Diseases, Ninth Revision codes were used to identify dementia diagnoses during follow-up and medical and psychiatric comorbidities in the 2 years prior to the index date. MAIN OUTCOMES AND MEASURES Dementia diagnosis in veterans who had experienced TBI with or without LOC and control participants without TBI exposure. RESULTS The study included 178 779 patients diagnosed with a TBI in the Veterans Health Administration health care system and 178 779 patients in a propensity-matched comparison group. Veterans had a mean (SD) age of nearly 49.5 (18.2) years at baseline; 33 250 (9.3%) were women, and 259 136 (72.5%) were non-Hispanic white individuals. Differences between veterans with and without TBI were small. A total of 4698 veterans (2.6%) without TBI developed dementia compared with 10 835 (6.1%) of those with TBI. After adjustment for demographics and medical and psychiatric comobidities, adjusted hazard ratios for dementia were 2.36 (95% CI, 2.10-2.66) for mild TBI without LOC, 2.51 (95% CI, 2.29-2.76) for mild TBI with LOC, 3.19 (95% CI, 3.05-3.33) for mild TBI with LOC status unknown, and 3.77 (95% CI, 3.63-3.91) for moderate to severe TBI. CONCLUSIONS AND RELEVANCE In this cohort study of more than 350 000 veterans, even mild TBI without LOC was associated with more than a 2-fold increase in the risk of dementia diagnosis. Studies of strategies to determine mechanisms, prevention, and treatment of TBI-related dementia in veterans are urgently needed.

Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.

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Objective It is unclear why late-life mood and anxiety disorders are highly undertreated, despite being common in older adults. Thus, this study determined the prevalence and key factors associated with non-use of mental health services among older community-dwelling adults with mood and anxiety disorders. Methods The study examined 348 participants aged 55 years and older who met criteria for prevalent DSM-IV mood and anxiety disorders from the National Comorbidity Survey Replication (NCS-R), a population-based probability sample. Analyses included frequency measures and logistic regression using weights and complex design-corrected statistical tests. Key factors associated with not using mental health services were determined in a final multivariable model using a systematic approach accounting for a comprehensive list of potential predictors. Results Approximately 70% of older adults with prevalent mood and anxiety disorders did not use services. Those who were from minority race/ethnic groups, not comfortable with discussing personal problems, who were married or cohabitating, and middle versus high income status had increased odds of not using mental health services. In addition, respondents with mild versus serious disorders, no chronic pain complaints, and low versus high perceived cognitive impairment had greater odds of non-use. Conclusions The results support improving perception of need and comfort to seek help, as well as increased screening and other prevention efforts, in order to combat the very high number of mood and anxiety disorders that go untreated in older Americans.