Testosterone levels decline as men age, as does cognitive function. Whether there is more than a temporal relationship between testosterone and cognitive function is unclear. Chemical castration ...studies in men with prostate cancer suggest that low serum testosterone may be associated with cognitive dysfunction. Low testosterone levels have also been observed in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). This paper reviews the current clinical evidence of the relationship between serum testosterone levels and cognitive function in older men.
A systematic literature search was conducted using PubMed and EMBASE to identify clinical studies and relevant reviews that evaluated cognitive function and endogenous testosterone levels or the effects of testosterone substitution in older men.
Low levels of endogenous testosterone in healthy older men may be associated with poor performance on at least some cognitive tests. The results of randomized, placebo-controlled studies have been mixed, but generally indicate that testosterone substitution may have moderate positive effects on selective cognitive domains (e.g. spatial ability) in older men with and without hypogonadism. Similar results have been found in studies in patients with existing AD or MCI.
Low endogenous levels of testosterone may be related to reduced cognitive ability, and testosterone substitution may improve some aspects of cognitive ability. Measurement of serum testosterone should be considered in older men with cognitive dysfunction. For men with both cognitive impairment and low testosterone, testosterone substitution may be considered. Large, long-term studies evaluating the effects of testosterone substitution on cognitive function in older men are warranted.
Early therapeutic interventions are essential to prevent Alzheimer Disease (AD). The association of several inflammation-related genetic markers with AD and the early activation of pro-inflammatory ...pathways in AD suggest inflammation as a plausible therapeutic target. Inflammatory Caspase-1 has a significant impact on AD-like pathophysiology and Caspase-1 inhibitor, VX-765, reverses cognitive deficits in AD mouse models. Here, a one-month pre-symptomatic treatment of Swedish/Indiana mutant amyloid precursor protein (APP
) J20 and wild-type mice with VX-765 delays both APP
- and age-induced episodic and spatial memory deficits. VX-765 delays inflammation without considerably affecting soluble and aggregated amyloid beta peptide (Aβ) levels. Episodic memory scores correlate negatively with microglial activation. These results suggest that Caspase-1-mediated inflammation occurs early in the disease and raise hope that VX-765, a previously Food and Drug Administration-approved drug for human CNS clinical trials, may be a useful drug to prevent the onset of cognitive deficits and brain inflammation in AD.
Until recently, clinicians and researchers have performed gait assessments and cognitive assessments separately when evaluating older adults, but increasing evidence from clinical practice, ...epidemiological studies, and clinical trials shows that gait and cognition are interrelated in older adults. Quantifiable alterations in gait in older adults are associated with falls, dementia, and disability. At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single‐ and dual‐task testing and that these cognitive disturbances assist in the prediction of future mobility loss, falls, and progression to dementia. This article reviews the importance of the interrelationship between gait and cognition in aging and presents evidence that gait assessments can provide a window into the understanding of cognitive function and dysfunction and fall risk in older people in clinical practice. To this end, the benefits of dual‐task gait assessments (e.g., walking while performing an attention‐demanding task) as a marker of fall risk are summarized. A potential complementary approach for reducing the risk of falls by improving certain aspects of cognition through nonpharmacological and pharmacological treatments is also presented. Untangling the relationship between early gait disturbances and early cognitive changes may be helpful in identifying older adults at risk of experiencing mobility decline, falls, and progression to dementia.
Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically ...examine the association of poor gait performance with incidence of dementia.
An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values.
Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P < .001 for any dementia, pooled HR = 1.79 with P < .001 for VaD, HR = 1.89 with P value < .001 for non-AD. Findings were weaker for predicting AD (HR = 1.03 with P value = .004).
This meta-analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD.
To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.
One thousand six hundred fifty-eight elderly ambulatory ...adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria.
During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval CI) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.
Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.
Aging is often associated with modifications of gait. Recent studies have revealed a strong relationship between gait and executive functions in healthy and pathological aging. We hypothesized that ...modification of gait due to aging may be related to changes in frontal lobe function.
Fourteen younger (27.0±3.6 years) and 14 older healthy adults (66.0±3.5 years) performed a motor imagery task of gait as well as a matched visual imagery task. Task difficulty was modulated to investigate differential activation for precise control of gait. Task performance was assessed by recording motor imagery latencies, eye movements, and electromyography during functional magnetic resonance imaging scanning.
Our results showed that both healthy older and young adults recruited a network of brain regions comprising the bilateral supplementary motor cortex and primary motor cortex, right prefrontal cortex, and cerebellum, during motor imagery of gait. We observed an age-related increase in brain activity in the right supplementary motor area (BA6), the right orbitofrontal cortex (BA11), and the left dorsolateral frontal cortex (BA10). Activity in the left hippocampus was significantly modulated by task difficulty in the elderly participants. Executive functioning correlated with magnitude of increases in right primary motor cortex (BA4) during the motor imagery task.
Besides demonstrating a general overlap in brain regions recruited in young and older participants, this study shows age-related changes in cerebral activation during mental imagery of gait. Our results underscore the importance of executive function (dorsolateral frontal cortex) and spatial navigation or memory function (hippocampus) in gait control in elderly individuals.
Quantifying spatio-temporal gait parameters in stationary and ambulatory geriatric settings may aid the early identification of potential fallers, as well as the documentation of illness-specific ...gait disorders and intervention-related changes in rehabilitative medicine. Bringing gait analysis out of the laboratory and into a clinical setting is the goal of the European GAITRite network group, initiated in 2003 in Geneva. To enhance reproducibility of gait measures and for better comparability of outcomes in clinical environments, a consensus on data collection was formulated and presented at the 2nd European GAITRite Meeting in Marseilles. The guidelines presented here are intended to facilitate network collaborations and to provide guidance to clinicians who wish to implement spatio-temporal gait analysis in clinical settings.
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