Hippocampal volume, early cognitive decline and gait variability: Which association?

BACKGROUND: In contrast to its prominent function in cognition, the involvement of the hippocampus in gait control is still a matter of debate. The present study aimed to examine the association of the hippocampal volume with mean values and coefficients of variation (CoV) of spatio-temporal gait parameters among cognitively healthy individuals (CHI) and patients with mild cognitive impairment (MCI). METHODS: A total of 90 individuals (47 CHI with a mean age of 69.7±3.6years and 48.9% women, and 43 MCI individuals with a mean age of 70.2±3.7years and 62.8% women) were included in this cross-sectional study. The hippocampal volume was quantified from a three-dimensional T1-weighted MRI using semi-automated software. Mean values and CoV of stride time, swing time and stride width were measured at self-selected pace with a 10m electronic portable walkway (GAITRite®). Age, gender, body mass index, number of drugs daily taken, Mini-Mental State Examination (MMSE) score, history of falls, walking speed and white matter signal-intensity abnormality scoring with Manolio scale were used as covariates. RESULTS: Patients with MCI had a lower MMSE score (P0.650). CONCLUSIONS: Our findings revealed a positive association between a greater (i.e., better morphological structure) hippocampal volume and a greater (i.e., worse performance) stride time variability among CHI, but not among MCI individuals

Vitamin D and Brain Imaging in the Elderly: Should we Expect Some Lesions Specifically Related to Hypovitaminosis D?

Hypovitaminosis D is associated with cognitive decline in the elderly, but the issue of causality remains unresolved. Definitive evidence would include the visualization of brain lesions resulting from hypovitaminosis D. The aim of the present article is to determine, through a literature review, the location and nature of possible brain disorders in hypovitaminosis D. We found limited brain-imaging data, which reported ischemic infarcts and white matter hyperintensities in hypovitaminosis D, though did not provide their specific location or report any focal atrophy. Based on the finding of executive dysfunctions (i.e., mental shifting and information updating impairments) in the presence of hypovitaminosis D, we suggest that hypovitaminosis D is associated with a dysfunction of the frontal-subcortical neuronal circuits, particularly the dorsolateral circuit. Further imaging studies are required to corroborate this assumption and to determine whether hypovitaminosis D results in degenerative and / or vascular lesions

Respective and combined effects of impairments in sensorimotor systems and cognition on gait performance: a population-based cross-sectional study.

BACKGROUND: Respective and combined effects of impairments in sensorimotor systems and cognition on gait performance have not been fully studied. This study aims to describe the respective effects of impairments in muscle strength, distance vision, lower-limb proprioception and cognition on the Timed Up & Go (TUG) scores (i.e., performed TUG [pTUG], imagined TUG [iTUG] and the time difference between these two tests [delta TUG]) in older community-dwellers; and to examine their combined effects on TUG scores. METHODS: Based on a cross-sectional design, 1792 community-dwellers (70.2±4.8 years; 53.6% female) were recruited. Gait performance was assessed using pTUG, iTUG and delta TUG. Participants were divided into healthy individuals and 15 subgroups of individuals according to the presence of impairment in one or more subsystems involved in gait control (i.e., muscle strength and/or distance vision and/or lower-limb proprioception and/or cognition [episodic memory and executive performance]). Impairment in muscle strength, distance vision and lower-limb proprioception was defined as being in the lowest tertile of performance. Impairment in cognition was defined as abnormal episodic memory and executive tests. RESULTS: A total of 191 (10.7%) exhibited impairment in muscle strength, 188 (10.5%) in distance vision, 302 (16.9%) in lower-limb proprioception, and 42 (2.3%) in cognition. Linear regressions showed that cognitive impairment as well as dual combinations of impairments were associated with increased pTUG (P CONCLUSION: Cognitive integrity is central for efficient gait control and stability, whereas lower-limb proprioception seems to be central for gait imagery

Association between dual task-related decrease in walking speed and real versus imagined Timed Up and Go test performance

Background and aims: To examine whether older people with markedly dual task-related decreases in walking speed—a marker of disturbed higher-level gait control and falls—have a larger discrepancy between real and imagined Timed Up and Go (TUG) test times than those with less dual task-related decreases in walking speed. Methods: Based on a prospective cross-sectional study, 193 older adults (mean age 77.4±5.9years; 44.0% women) referred to and consecutively assessed at a Swiss university clinic for a gait analysis to assess either gait disorders, fall risk or memory disorders were included. For all participants, walking speed was measured using a GAITRite® electronic walkway system during usual walking at self-selected pace and while dual tasking (i.e., usual walking and simultaneously counting backwards out loud). In addition, real Timed Up and Go (TUGr) and imagined Timed Up and Go (TUGi) (i.e., the time needed to imagine performing the TUGr) times were measured with a stopwatch. Differences between both walking conditionsfor walking speed (delta of walking speed) and both TUG conditions (delta of TUG time) were calculated. Age, gender, height, total number drugs taken per day, daily use of psychoactive drugs, use of walking aid, history of falls, Mini-Mental State Examination score, near vision and education level were used as covariables in this analysis. Results: Participants were categorized into two groups based on being in the lowest tertian (i.e., <33%: group A corresponding to participants undisturbed by dual task) or not (i.e., ≥33%: group B corresponding to participants disturbed by dual task) of the delta of walking speed. In both groups, TUGr and TUGi times were similar (P=.169 and P=.839). In both groups, TUGi was faster than TUGr (P<.001). Delta of TUG time was significantly greater in group B compared to group A (P<.001). After adjustment for all covariables, only the delta of walking speed was significantly associated with the delta of TUG time (P=<.001). Stepwise backward regression showed that polypharmacy (P=.017) and delta of walking speed (P=<.001) were associated with an increase in delta of TUG time, whereas an increased MMSE score (P=.030) was associated with a decrease in delta of TUG time. Conclusion: These findings show that a large discrepancy between real and imagined TUG performances is significantly correlated with a decrease in walking speed while dual tasking, and thus may also be a surrogate marker of disturbed higher-level gait control. The quickly and easily performed TUG tests may represent a feasible, practical screening tool for early detection of higher-level gait disorders in older adult

Serum vitamin D status is associated with the presence but not the severity of primary open angle glaucoma.

OBJECTIVES: Vitamin D is involved in visual health and function. Our objective was to determine whether age-related vitamin D insufficiency was associated with the presence and the severity of primary open angle glaucoma (POAG) in a case-control study of older adults. STUDY DESIGN: Case-control study. MAIN OUTCOME MEASURES: One hundred fifty cases diagnosed with moderate-to-severe POAG (mean, 75.1±8.5 years; 42.0% female) and 164 healthy controls (mean, 73.0±7.9 years; 59.8% female) were included. POAG diagnosis was based on classical diagnostic criteria of optic nerve cupping and/or RNFL thinning, measured with optical coherence tomography. Severe POAG was defined as Humphrey visual field mean deviation (MD) worse than -12dB. Vitamin D insufficiency was defined as serum 25OHD≤75nmol/L. Age, gender, mean arterial pressure, vitamin D supplementation, visual acuity, and intraocular pressure were used as potential confounders. RESULTS: POAG cases had lower mean serum 25OHD concentration than controls (42.9±25.7nmol/L versus 49.4±29.5nmol/L, P=0.039) and a greater prevalence of vitamin D insufficiency (90.7% versus 82.3%, P=0.032). Increased mean serum 25OHD concentrations were associated with lower POAG frequency, even after adjustment for potential confounders (OR=0.89 per 10nmol/L of 25OHD, P=0.045). Similarly, vitamin D insufficiency was associated with POAG (OR=2.09, P=0.034). Among POAG cases, no 25OHD difference was observed between moderate and severe POAG cases (respectively, 39.2±23.3nmol/L versus 45.1±26.7nmol/L, P=0.188); and no between-group difference regarding the prevalence of vitamin D insufficiency (88.9% versus 94.0%, P=0.313). CONCLUSIONS: Decreased serum 25OHD concentration was associated with POAG. There was no 25OHD difference between moderate and severe POAG

Gait control: a specific subdomain of executive function?

<p>Abstract</p> <p>Background</p> <p>Few studies looked at the association between gait variability and executive subdomains (ESD). The aim of this study was to examine the association between ESD (i.e., information updating and monitoring) and stride time variability among healthy older adults.</p> <p>Methods</p> <p>Seventy-eight healthy older adults (mean age 69.9 ± 0.9 years, 59% women) were divided into 3 groups according to stride time variability (STV) tertiles while steady state walking. Coefficient of variation of stride time was used as a marker of STV. Scores on cognitive tests evaluating information updating and monitoring (Digit Span test), mental shifting (Trail Making Test part A and part B) and cognitive inhibition (Stroop Color Word test) were used as measures of ESD.</p> <p>Results</p> <p>The full adjusted and the stepwise backward logistic regression models showed that the highest tertile (i.e., the worst performance) of STV was only associated with lower Digit Span performance (Odds ratio = 0.78 with P = 0.020 and Odds ratio = 0.81 with P = 0.019).</p> <p>Conclusions</p> <p>Information updating and monitoring are associated with STV in the sample of studied participants, suggesting that walking may be a complex motor task depending specifically of this subdomain of executive functions.</p

Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer's Disease: A 7-Year Follow-up

Background. Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. Our objective was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older. Methods. Four hundred and ninety-eight community-dwelling women (mean, 79.8 ± 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into three groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer's disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. Results. Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 ± 19.3 μg/wk) than nondemented (n = 361; mean intake = 59.0 ± 29.9 μg/wk, p = .027) or those who developed other dementias (n = 67; mean intake = 63.6 ± 38.1 μg/wk, p = .010). There was no difference between other dementias and no dementia (p = .247). Baseline vitamin D dietary intakes were associated with the onset of AD (adjusted odds ratio = 0.99 [95% confidence interval = 0.98-0.99], p = .041) but not with other dementias (p = .071). Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined (adjusted odds ratio = 0.23 [95% confidence interval = 0.08-0.67], p = .007). Conclusions. Higher vitamin D dietary intake was associated with a lower risk of developing AD among older wome

Association of angiitis of central nervous system, cerebral amyloid angiopathy, and Alzheimer’s disease: Report of an autopsy case

The association of angiitis of central nervous system (ACNS) with cerebral amyloid angiopathy (CAA) suggests a physiopathological relationship between these two affections. Few cases are reported in patients with Alzheimer’s disease (AD). We describe here a clinicopathological case associating ACNS, CAA, and AD. We discuss the aetiology of ACNS and its relationship with cerebral deposition of beta A4 amyloid protein (βA4)

Alzheimer's disease - input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial

BACKGROUND: Current treatments for Alzheimer\u27s disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine. METHODS: The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] &lt; 30 ng/mL), normocalcemia (i.e., serum calcium &lt; 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer\u27s Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up &amp; Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone. DISCUSSION: The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01409694