Smaller Brain Tissue Volumes Research Articles

The Effect of Hearing Aid Use on the Association Between Hearing Loss and Brain Structure in Older Adults.

Recent studies have shown an association between poorer hearing thresholds and smaller brain tissue volumes in older adults. Several underlying causal mechanisms have been opted, with a sensory deprivation hypothesis as one of the most prominent. If hearing deprivation would lead to less brain volume, hearing aids could be hypothesized to moderate this pathway by restoration of hearing. This study aims to investigate whether such a moderating effect of hearing aids exists. The authors conducted a cross-sectional study involving aging participants of the population-based Rotterdam Study. Hearing aid use was assessed by interview and hearing loss was quantified using pure-tone audiometry. Total brain volume, gray matter and white matter volume and white matter integrity [fractional anisotropy (FA) and mean diffusivity] were measured using magnetic resonance imaging. Only participants with a pure tone average at 1, 2, and 4 kHz (PTA1,2,4) of ≥35 dB HL were included. Associations of hearing loss with brain volume and global measures of white matter integrity were analyzed using linear regression, with hearing aid use and interaction between hearing aid use and PTA1,2,4 included as independent variables. Models were adjusted for age, sex, time between audiometry and magnetic resonance imaging, level of education, and cardiovascular risk factors. Out of 459 included participants with mean age (range) 70.4 (52 to 92) 41% were female. Distributions of age and sex among hearing aid users (n = 172) did not significantly differ from those without hearing aids. PTA1,2,4 was associated with lower FA, but not with a difference in total brain volume, gray matter volume, white matter volume, or mean diffusivity. Interaction between hearing aid use and PTA1,2,4 was not associated with FA or any of the other outcome measures. Additional analysis revealed that interaction between hearing aid use and age was associated with lower FA. We found no evidence for a moderating effect of hearing aids on the relationship between hearing loss and brain structure in a population of older adults. However, use of hearing aids did appear as an effect modifier in the association between age and white matter integrity. Future longitudinal research is needed to clarify these results.

Blood Pressure Variation and Subclinical Brain Disease

BackgroundLarge blood pressure (BP) variability may contribute to stroke and dementia, but the mechanisms are largely unknown. ObjectivesThis study investigated the association of BP variation, considering its magnitude and direction, with the presence and progression of subclinical brain disease in the general population. MethodsThis study included 2,348 participants age ≥55 years from a prospective cohort study. BP was measured at each visit every 3 to 4 years from 1990 onward. Brain magnetic resonance imaging (MRI) was performed at all visits from 2005 onward. The authors primarily assessed variation as the absolute difference in BP divided by the mean over 2 sequential visits for both systolic BP (SBP) and diastolic BP (DBP), and further assessed the direction of the variation. The authors investigated the multivariate-adjusted associations of BP variation with subsequent measurements of MRI markers of cerebral small vessel disease, brain tissue volumes, and white matter microstructural integrity. Longitudinal changes in these markers also were assessed. ResultsA large SBP variation (top vs. bottom tertiles), measured on average 7 years preceding brain MRI, was associated with higher odds of having severe white matter hyperintensities (WMH) (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.21 to 1.43), lacunes (OR: 1.25; 95% CI: 1.04 to 1.48), and microbleeds (OR: 1.16; 95% CI: 1.03 to 1.31). Similarly, this variation was associated with smaller total brain volume and worse white matter microstructural integrity (all p < 0.001). A large SBP variation was also associated with the progression of WMH (rate ratio [RR]: 1.14; 95% CI: 1.02 to 1.27). Higher burdens of these brain imaging markers were observed with both large rises and falls in SBP. Similar findings were observed for DBP variation. ConclusionsElevated BP variation was associated with a wide range of subclinical brain structural changes, including MRI markers of cerebral small vessel disease, smaller brain tissue volumes, and worse white matter microstructural integrity. These subclinical brain changes could be the underlying mechanisms linking BP variation to dementia and stroke.

Associations of vitamin D deficiency with MRI markers of brain health in a community sample.

Vitamin D deficiency has been linked to an increased risk of dementia. To strengthen this evidence and establish whether vitamin D can indeed play a role in early prevention of neurodegeneration, knowledge on underlying pathways is crucial. Therefore, we aimed to investigate the association of vitamin D status with brain tissue volumes, hippocampus volume, white matter integrity, and markers of cerebral small vessel disease (CSVD) in a dementia-free population. In this cross-sectional analysis, 2,716 participants free of dementia from the population-based Rotterdam Study underwent serum 25(OH)D concentration assessment and brain magnetic resonance imaging (MRI) scanning between 2006 and 2009. Outcomes of interest included brain tissue volume (total, white matter, grey matter and hippocampus volume), white matter integrity (fractional anisotropy (FA) and mean diffusivity (MD)), and markers of CSVD (white matter hyper intensity (WMH) volume, presence of lacunes and microbleeds). Associations between vitamin D status, both in categories and continuous, and these brain measurements were assessed using multivariable linear and logistic regression models, adjusting for lifestyle and other disease risk factors. We observed that vitamin D deficiency (25(OH)D<30nmol/L) was independently associated with smaller brain tissue volume, smaller white matter volume and smaller hippocampus volume as compared to a sufficient vitamin D status (≥50nmol/L). Vitamin D per 10nmol/L increment and an insufficient (30-50nmol/L) as compared to sufficient vitamin D status were not associated with the brain measures of interest. Moreover, vitamin D status was not associated with grey matter volume, white matter integrity or CSVD markers. In this dementia-free population, vitamin D deficiency was associated with a smaller brain tissue volume and hippocampus volume. More research, in particular with a longitudinal design, is needed to further elucidate the role of vitamin D in neurodegeneration.

From neuroleptics to neuroscience and from Pavlov to psychotherapy: more than just the "emperor's new treatments" for mental illnesses?

“The drugs don't work” was one of the hit singles from The Verve's album Urban Hymns , released in 1997. The song was written by lead singer Richard Ashcroft relating to his drug abuse, but it might well relate to the modern treatments for mental illnesses. More than half a century after neuroleptics, antidepressants, benzodiazepines, antipsychotics, behavior therapy, and cognitive treatment were introduced, it is prudent to ask whether “the drugs don't work”. During the past 50 years, the industrialized world has seen a dichotomy between loudly proclaimed therapeutic breakthroughs and rapidly rising numbers of people on disability payments because of mental illness. We hear that antipsychotic, antidepressant, and anti‐anxiety drugs as well as behavior therapy and newer treatments have radically improved what was described as a dismal fate of people suffering from mental disorders. Simultaneously, the percentage of disabled mentally ill patients in the USA has risen by more than 600% since the 1950s (Whitaker, 2010) and similar rates are seen in European countries. Most epidemiologists agree that this “epidemic” is not caused by increased incidence. Moreover, the once rapid succession of new therapeutic developments seems to have halted, at least in pharmacology, as big companies are withdrawing from research on mental disorders. How can this apparent contradiction be explained? Could it be that therapeutic progress is much less than we think or are being told? Could it be that the course of depression, anxiety, schizophrenia, or ADHD has been altered for the worse? Could it be that we cannot make therapeutic progress because the concept of mental illness and its treatment is deeply flawed? There are strong reasons to assume that all three suspicions are in fact true. So, what do we know about the efficiency of pharmacological and psychological treatments? In regard to short‐term outcomes, pharmacotherapy is clearly …

Metabolic syndrome, prediabetes, and brain abnormalities on mri in patients with manifest arterial disease: the SMART-MR study.

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors leading to atherosclerosis and diabetes. Diabetes is associated with both structural and functional abnormalities of the brain. MetS, even before diabetes is diagnosed, may also predispose to cerebral changes, probably through shared mechanisms. We examined the association of MetS with cerebral changes in patients with manifest arterial disease. Cross-sectional data on MetS and brain MRI were available in 1,232 participants with manifest arterial disease (age 58.6 ± 10.1 years; 37% MetS). Volumes of brain tissue, ventricles, and white matter hyperintensities (WMH) were obtained by automated segmentation and expressed relative to intracranial volume. Infarcts were distinguished into lacunar and nonlacunar infarcts. The presence of MetS (n = 451) was associated with smaller brain tissue volume (B -0.72% [95% CI -0.97, -0.47]), even in the subgroup of patients without diabetes (B -0.42% [95% CI -0.71, -0.13]). MetS was not associated with an increased occurrence of WMH or cerebral infarcts. Impaired glucose metabolism, abdominal obesity, and elevated triglycerides were individual components associated with smaller brain volume. Obesity and hypertriglyceridemia remained associated with smaller brain volume when patients with diabetes were excluded. Hypertension was associated with an increased occurrence of WMH and infarcts. In patients with manifest arterial disease, presence of MetS is associated with smaller brain volume, even in patients without diabetes. Screening for MetS and treatment of its individual components, in particular, hyperglycemia, hypertriglyceridemia, and obesity, may prevent progression of cognitive aging in patients with MetS, even in a prediabetic stage.

Relapse Duration, Treatment Intensity, and Brain Tissue Loss in Schizophrenia: A Prospective Longitudinal MRI Study

Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question. The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years. Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity. Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.

Migraine, depression, and brain volume

To examine the joint association of migraine headache and major depressive disorder on brain volume in older persons without dementia. Participants (n = 4,296, 58% women) from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study were assessed for migraine headache in 1967-1991 (age 51 years [range 33-65]) according to modified International Classification of Headache Disorders-II criteria. In 2002-2006 (age 76 years [range 66-96]), lifetime history of major depressive disorder (depression) was diagnosed according to DSM-IV criteria, and full-brain MRI was acquired, which was computer postprocessed into total brain volume (TBV) (gray matter [GM], white matter [WM], white matter hyperintensities) and CSF volume for each study subject. We compared brain tissue volumes by headache categories with or without depression using linear regression, adjusting for intracranial volume and other factors. Compared with the reference group (no headache, no depression) TBV and WM and GM volumes were smaller in those with both migraine and depression (TBV -19.2 mL, 95% confidence interval [CI] -35.3, -3.1, p = 0.02; WM -12.8 mL, CI -21.3, -4.3, p = 0.003; GM -13.0 mL, CI -26.0, 0.1, p = 0.05) but not for those with migraine alone (TBV 0.4 mL, WM 0.2 mL, GM 0.6 mL) or depression alone (TBV -3.9 mL, WM -0.9 mL, GM -2.9 mL). Reporting both migraine and major depressive disorder was associated with smaller brain tissue volumes than having one or neither of these conditions. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae. Nonetheless, the number of subjects in the current study is relatively small and these findings need to be confirmed in future studies.

Brain Morphology at Entry into Treatment for Alcohol Dependence Is Related to Relapse Propensity

We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers. Individuals in alcohol dependence treatment (n = 75) underwent magnetic resonance imaging approximately 6 ± 4 days after their last alcoholic drink, and 40 age-matched nonsmoking light drinkers (LD) were studied as control subjects. At follow-up 7.8 ± 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and LD. Compared with LD, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex and bilaterally in the thalamus and adjacent subcortical white matter (WM) and had larger volume in the left lateral orbitofrontal region. Compared with LD, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared with future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities. At entry into alcohol dependence treatment, the brain structure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry might confer greater risk for resumption of hazardous drinking after treatment and might contribute to the definition of a neurobiological relapse risk profile in alcohol dependence.

Long-term Antipsychotic Treatment and Brain Volumes

Progressive brain volume changes in schizophrenia are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for schizophrenia patients, may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders, it is imperative to determine their long-term effects on the human brain. To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change. Predictors of brain volume changes were assessed prospectively based on multiple informants. Data from the Iowa Longitudinal Study. Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each patient had 3 scans (≥2 and as many as 5) over 7.2 years (up to 14 years). Brain volumes. During longitudinal follow-up, antipsychotic treatment reflected national prescribing practices in 1991 through 2009. Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors. More antipsychotic treatment was associated with smaller gray matter volumes. Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted. Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.