Caroline L. Phillips

Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias

Background: The association between antecedent head injury and AD is inconsistent. Objective: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE ε4 as risk factors for dementia. Methods: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. Results: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE ε4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more ε4 alleles. Conclusions: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

Vitamin D and risk of cognitive decline in elderly persons

BACKGROUND To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Risk Factors for Late-Life Suicide: A Prospective, Community-Based Study

Despite the fact that people age 65 and older have the highest rates of suicide of any age-group, late-life suicide has a low prevalence, making it difficult to conduct prospective studies. The authors examined risk factors for late-life suicide on the basis of general information collected directly from older subjects participating in a community-based prospective study of aging, the Established Populations for Epidemiologic Studies of the Elderly. Demographic variables, presence of a relative or friend to confide in, alcohol use, and sleep quality were assessed at baseline interview. Baseline and follow-up data were used to determine physical, cognitive, and affective functioning, as well as medical status. Of 14,456 people, 21 committed suicide over the 10-year observation period. Depressive symptoms, perceived health status, sleep quality, and absence of a relative or friend to confide in predicted late-life suicide. Suicide victims did not have greater alcohol use and did not report more medical illness or physical impairment. This study provided additional information about the context of late-life depression that also contributes to suicidal behavior: poor perceived health, poor sleep quality, and limited presence of a relative or friend to confide in.

Anemia and Hemoglobin Levels in Older Persons: Relationship with Age, Gender, and Health Status

To determine the relationship of hemoglobin levels and anemia with age and health status in older adults.

Serum albumin in older persons: Relationship with age and health status

We analyzed data from 4115 persons aged 71 years and older who had blood drawn at a home visit in three communities to examine the cross-sectional distribution of serum albumin and correlates of hypoalbuminemia. Mean albumin was lower among older persons, from 41.6 g/l in men aged 71-74 years to 38.5 g/l in men 90 years or older, and from 41.1 g/l to 38.9 g/l in women of the same ages, respectively. Hypoalbuminemia (albumin less than 35 g/l) was observed in 3.1% of subjects. Hypoalbuminemia and lower serum albumin were independently associated with anemia, recent diagnosis of cancer, two or more limitations in activities of daily living, residence in a nursing home, heavy cigarette smoking (greater than 1 pack/day), and older age. A 10-year age increment was associated with 0.8 g/l lower serum albumin and odds ratio of 1.56 (95% CI 1.14, 2.13) for hypoalbuminemia after adjusting for demographic factors and health status. Characteristics associated with serum albumin may confound the reported relationship between serum albumin and mortality.

Magnetization transfer imaging, white matter hyperintensities, brain atrophy and slower gait in older men and women

OBJECTIVE To assess whether markers of micro- and macrostructural brain abnormalities are associated with slower gait in older men and women independent of each other, and also independent of health-related conditions and of behavioral, cognitive and peripheral function. METHODS Magnetization transfer ratio [MTR], white matter hyperintensities [WMH], brain atrophy [BA] and brain infarcts [BI] were measured in 795 participants of the AGES-Reykjavik Study cohort (mean 75.6 years, 58.9% women). RESULTS In women, lower MTR, higher WMH and BA, but not BI, remained associated with slower gait independent of each other and of other covariates. In men, WMH and BA, but not MTR or BI, remained associated with slower gait independently of each other. Only muscle strength, executive control function and depression test scores substantially attenuated these associations. INTERPRETATIONS MTR in older adults may be an important additional marker of brain abnormalities associated with slower gait. Studies to explore the relationship between brain micro- and macrostructural abnormalities with gait and the role of mediating factors are warranted.

Electrocardiographic PR Interval and Adverse Outcomes in Older Adults The Health, Aging, and Body Composition Study

Background— The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. Methods and Results— The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02–1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04–1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11–1.93). PR interval was not associated with increased all-cause mortality. Conclusions— We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.Background—The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. Methods and Results—The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02–1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04–1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11–1.93). PR interval was not associated with increased all-cause mortality. Conclusions—We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

Diabetes, peripheral neuropathy, and lower-extremity function ☆

OBJECTIVE Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. RESEARCH DESIGN AND METHODS This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. RESULTS AND CONCLUSION One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF.

Risk Factors Associated With Incident Cerebral Microbleeds According to Location in Older People The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study

IMPORTANCE The spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people. OBJECTIVE To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location. DESIGN, SETTING, AND PARTICIPANTS We enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011. EXPOSURES Lifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides. MAIN OUTCOMES AND MEASURES Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep. RESULTS During a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a decreased triglyceride level (RR per 1-SD decrease in natural logarithm-transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly associated with an increased risk for lobar CMBs exclusively but not for deep CMBs. CONCLUSIONS AND RELEVANCE Lifestyle and lipid risk profiles for CMBs were similar to those for symptomatic intracerebral hemorrhage and differed for lobar and deep CMBs. Modification of these risk factors could have the potential to prevent new-onset CMBs, particularly those occurring in a lobar location.

Cerebral Small Vessel Disease and Association With Higher Incidence of Depressive Symptoms in a General Elderly Population: The AGES-Reykjavik Study

OBJECTIVE The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) leads to depressive symptoms by disruption of brain structures involved in mood regulation. However, longitudinal data on the association between CSVD and depressive symptoms are scarce. The authors investigated the association between CSVD and incident depressive symptoms. METHOD Longitudinal data were taken from the Age, Gene/Environment Susceptibility-Reykjavik Study of 1,949 participants free of dementia and without baseline depressive symptoms (mean age: 74.6 years [SD=4.6]; women, 56.6%). MRI markers of CSVD, detected at baseline (2002-2006) and follow-up (2007-2011), included white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces, and total brain parenchyma volume. Incident depressive symptoms were defined by a score ≥6 on the 15-item Geriatric Depression Scale and/or use of antidepressant medication. RESULTS Depressive symptoms occurred in 10.1% of the participants. The association for a greater onset of depressive symptoms was significant for participants with 1 standard deviation increase in white matter hyperintensity volume over time, new subcortical infarcts, new Virchow-Robin spaces, 1 standard deviation lower total brain volume at baseline, and 1 standard deviation decreased total brain volume over time, after adjustments for cognitive function and sociodemographic and cardiovascular factors. Results were qualitatively similar when change in the Geriatric Depression Scale score over time was used as the outcome instead of incident depressive symptoms. CONCLUSIONS Most markers of progression of CSVD over time and some markers of baseline CSVD are associated with concurrently developing new depressive symptoms. These findings support the vascular depression hypothesis.