Cognitive estimation in mild Alzheimer’s disease

Summary In everyday life, we often estimate rather than know. We investigated in an experimental approach modality-specific cognitive estimation in patients with mild Alzheimer’s disease (AD). Estimation of weight, size, number, and time prior and subsequent to observation of a moving object was assessed in healthy controls (HC; n = 49; 62.5 ± 7.8 years (mean ± standard deviation); MMSE 29.2 ± 1.1) and patients with AD (NINCDS-ADRDA, DSM IV; n = 42; 75.0 ± 9.5 years; p < 0.001 to HC; MMSE 22.8 ± 2.9; p < 0.001 to HC). In HC none of the estimation tasks correlated with age or general intellectual ability. AD patients were impaired for estimation of time and weight while estimation of number, size, and distance was not impaired. Estimation of time that a marble will need to roll down a marble track was associated with lower scores for verbal fluency and higher scores for clock drawing in the AD group and estimation of time subsequent to observation was associated with higher scores in clock drawing. Time estimation for moving objects as well as the ability to correct oneself on observation is impaired in patients with very mild AD. This argues for caution in tasks such as car driving already in this stage. Errors in estimation of time observed indicate temporo-parietal impairment while errors on estimation prior to observation of the moving object indicate additional frontal lobe impairment.     

Impairment of sensory-motor plasticity in mild Alzheimer’s disease

BackgroundPrimary motor cortex (M1) is relatively spared in the early stages of Alzheimer’s disease (AD).ObjectiveAim of the present study was to investigate whether abnormal M1 synaptic plasticity is present at an early stage of AD. We employed an electrophysiological protocol, named rapid paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies corticospinal excitability and short latency afferent inhibition (SAI).MethodsWe studied 10 patients with a diagnosis of probable mild AD according to the Mini Mental State Examination score (minimum 21) and 14 age-matched control subjects. Motor evoked potentials (MEP) amplitudes and short-afferent inhibition (SAI) were measured at baseline before and for up to 60 min after 5Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an inter-stimulus interval of 25 ms.ResultsBaseline SAI was significantly reduced in AD patients. In the control subjects rPAS induced a significant increase in MEP amplitudes and a decrease of SAI in the APB muscle persistently for up to 1 h. Conversely 5Hz-rPAS did not induce any significant changes in MEP amplitudes and SAI in mild AD patients.ConclusionsSensory-motor plasticity is impaired in the motor cortex of AD at an early stage of the disease.     

Taste in mild cognitive impairment and Alzheimer’s disease

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the “taste strips”. Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.     

Heterogenous mechanisms of mild cognitive impairment in Parkinson’s disease

Mild cognitive impairment in Parkinson disease (PD-MCI) shows heterogeneity in the clinical presentation, neuropsychology, neuroimaging, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical systems. Prospective studies using specific biomarkers, including amyloid imaging and CSF biomarkers are important for the diagnosis and prognostic assessment of early cognitive deficits in PD patients.     

A longitudinal cardiovascular autonomic function study in mild Guillain-Barré syndrome

To identify subclinical autonomic dysfunction in mild Guillain-Barré syndrome (GBS), a set of autonomic function tests was serially performed for up to 6 months in 5 GBS patients with mild disability at the nadir. Parasympathetic autonomic function tests consisted of Valsalva ratio and R-R interval variation during rest and deep breathing. Sympathetic autonomic function was evaluated by blood pressure responses to sustained handgrip, hand immersion in ice water, and active standing. The results showed that abnormal parasympathetic and sympathetic function was frequently encountered in all 5 patients during the acute stage of the illness. Autonomic dysfunction occurred both in axonal and demyelinating types of GBS. There was a trend of improvement in most autonomic function tests after 3 months, comparable to the recovery of motor function. In conclusion, subclinical autonomic dysfunction was present in mild GBS. It was temporary and would resolve spontaneously.     

How well do caregivers detect mild cognitive change in Parkinson's disease?

Using the Cambridge Behavior Inventory‐Revised, this study evaluated the relationship between caregiver ratings of cognitive change and neuropsychological performance. In sixty‐one nondemented patients with Parkinson's Disease (PD; mean age = 64.5 years, MMSE = 28.7), 62% met criteria for mild cognitive impairment. This group were rated as having more overall change as well as memory and behavior change. Caregiver ratings were related to poorer psychomotor speed, learning/memory, language, and executive functioning. The capacity for caregivers to rate mild cognitive change in PD may be useful to assist in early screening and intervention approaches. © 2010 Movement Disorder Society     

Infections and course of disease in mild forms of Guillain-Barré syndrome

OBJECTIVE: Twenty-eight percent of patients with the Guillain-Barré syndrome remain able to walk unaided. Studying patients with the mild form of Guillain-Barré syndrome can further contribute to knowledge of the spectrum of the syndrome and explore whether this subgroup may need treatment with IV immunoglobulin. METHODS: Patients fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke criteria for Guillain--Barré syndrome were included in a nationwide survey over a 2-year period. Clinical characteristics and serum samples were collected prospectively. In addition, a questionnaire was completed concerning the course and outcome of the disease. RESULTS: A total of 139 patients were included. Nineteen of the patients (14%) included were mildly affected, and 120 (86%) were severely affected. Infections with Epstein-Barr virus were found more frequently in mildly affected patients (p = 0.02). Antiganglioside antibodies were less frequently found in the mildly affected patients (p = 0.03). The degree of severity of the disease between mildly and severely affected patients was different on the day of admission (p < 0.01). Thereafter, the groups showed a remarkably similar rate of progression. Thirty-eight percent of mildly affected patients report problems in hand function and an inability to run at 3 and 6 months (all women, p = 0.02). CONCLUSION: The difference in severity of Guillain--Barré syndrome seems to be determined in an early phase of the disease. Preceding infections and antiganglioside antibodies may influence the initial immune attack, determining the severity of the disease. The presence of residual signs in patients with mild disease may advocate the use of early treatment in mildly affected patients.     

Abnormal visual search in mild cognitive impairment and Alzheimer’s disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined the status of visual attention-related processing in such patients in relation to healthy older adults and patients with Alzheimer’s disease (AD) by measuring performance on a computer-based visual search task. We tested 20 older adult control participants, 13 patients with amnestic mild cognitive impairment and 12 patients with AD. Patients with AD and with MCI exhibited a significant detriment in visual search performance compared to the older adult controls. The deficit in visual search was greater for the patients with AD than the patients with MCI. The pattern of results displayed by the MCI group indicates that patients who appear clinically to suffer only from a deficit in memory also display a deficit in visual attention-related processing, which although not as severe as those with AD, represents a significant detriment in such performance compared to that seen in healthy ageing.     

Does CPAP treatment in mild obstructive sleep apnea affect blood pressure?

ObjectivesObstructive sleep apnea (OSA) is associated with significant cardiovascular (CV) morbidity. Continuous positive airway pressure (CPAP) is the standard treatment for moderate to severe OSA, resulting in a reduction in CV morbidity. No studies have compared CV outcomes between CPAP and no CPAP in mild OSA (5 ? AHI < 15).MethodsRetrospective cohort study of subjects (age ? 18) with mild OSA diagnosed between 2004 and 2006. Subjects with a history of hypertension, angina, stroke and smoking were excluded. Subjects were stratified into two groups: CPAP (n = 93) or no CPAP (n = 162). The mean blood pressures (MBP) were compared 2 years after the diagnosis of OSA was established.ResultsUnmatched for covariates (age, sex, BMI, neck circumference, AHI, arousal index and family h/o CV disorders), subjects with mild OSA on CPAP had a 1.97 point reduction, and no CPAP resulted in a 9.61 point elevation (p < 0.0001) in MBP. With propensity score matching for covariates, the mean difference in MBP was ?1.97 (95% CI: ?14.03, ?9.92; p < 0.0001) with a sensitivity analysis of 2.646.ConclusionThis study shows an elevation of the MBP in mild OSA patients who were not treated with CPAP. CPAP treatment in mild OSA patients decreased the MBP over a 2-year period.     

Plasma lipids metabolism in mild cognitive impairment and Alzheimer’s disease

Objectives: Expression of phospholipids and related molecules could provide panels of multiple biomarkers searching for the signature of Alzheimer’s disease (AD). The aim of the present study was to quantify ten phospholipids and simultaneously determine phospholipase A₂ (PLA₂) activity in blood of mild cognitive impairment (MCI) and AD patients.

Methods: Thirty-four AD, 20?MCI and 25 controls were enrolled. The phospholipids where analysed using the AbsoluteIDQ^® p180 Kit. PLA₂ activities were accessed in platelets by a radio-enzymatic assay.

Results: The study failed to fix the ten phospholipids as a panel to predict AD; the levels of PCaaC36:6, PCaaC40:6 and C16:1-OH were lower in MCI than in controls (P?=?0.041, P?=?0.012, P?=?0.044 respectively). PCaaC40:2 levels were lower in MCI than in AD (P?=?0.041). The converters MCI-AD showed at baseline lower levels of PCaaC40:2 (P?=?0.050) and PCaaC40:6 (P?=?0.037) than controls. iPLA₂ activity was reduced in AD and MCI than in controls (P?2 (r?=?0.680; P?=?0.001) and sPLA₂ (r?=?0.601; P?=?0.004); PCaaC40:1 and iPLA₂ (r?=?0.503; P?=?0.020); PCaaC40:6 and tPLA₂ (r?=?0.532; P?=?0.013) and sPLA₂ (r?=?0.523; P?=?0.015).

Conclusions: Lipids metabolites in plasma might indirectly indicate changes in neuronal membrane and this deregulation can outline the transition between healthy and diseased brains.     

Modeling sports-related mild traumatic brain injury in animals—A systematic review

Sports-related head trauma has emerged as an important public health issue, as mild traumatic brain injuries (mTBIs) may result in neurodegenerative disorders such as chronic traumatic encephalopathy (CTE). Research into mTBI and CTE pathophysiology are difficult to undertake in athletes, with observational trials and post-mortem analysis the current mainstays. Thus, animal models play an important role in the study of mTBI, however, traditional animal models have focused on acute, severe injuries rather than the more typical mTBI's seen in sport injuries. Recently, a number of animal models have been developed that are both appropriately scaled and biomechanically relevant to the forces sustained by athletes. This review aimed to examine the literature for variables included in these animal models, and the resulting neurotrauma as evidenced by pathology and behavioral deficits. A systematic search of the literature was performed in multiple electronic databases. The inclusion criteria required mimicry of athlete mTBI conditions: freedom of head movement, lack of surgical alteration of the skull, and application of direct contact force. Studies were analyzed for variables including apparatus design features (impact force, change in animal head velocity, and kinetic energy transfer to the head), demonstrated pathology (phosphorylated tau, TDP-43 aggregation, diffuse axonal injury, gliosis, cytokine inflammation response, and genetic integrity), and behavioral changes. These studies suggested that appropriate animal models can assist in understanding the pathological and functional outcomes of athlete mTBI, and could be used as a platform for future studies of diagnostic/prognostic markers and in the development of treatment interventions.     

Diagnostic and screening power of neuropsychological testing in detecting mild cognitive impairment in Parkinson’s disease

Prevalence of mild cognitive impairment (MCI) in Parkinson’s disease (PD) is variable likely due to methodological differences in classification criteria and lack of consensus about neuropsychological tests used for cognitive profiling. The main objective of our study was to identify the most suitable neuropsychological tests and determine their screening and diagnostic cutoff scores for PD-MCI. A series of 104 consecutive PD patients performed an extensive neuropsychological evaluation. Individual test values were converted into Z-scores using relative published normative data. According to published criteria, PD patients were categorized as PD-CNT (PD without cognitive impairment), PD-MCI (patients performing ?1.5 SDs below the mean score in at least one cognitive domain), and PDD. We used receiver operating characteristic (ROC) curves and K-means clustering analyses to calculate the best discriminating power of each neuropsychological tests in detecting PD-MCI. PD patients were categorized as follows: 55 PD-CNT (53 %), 34 PD-MCI (33 %), and 15 PDD (14 %). PD-MCI had lower education, longer disease duration and greater frequency of hallucinations than PD-CNT. We found that only the Trail Making test, Rey-Osterrieth Complex Figure Test (ROCF) copy, Frontal Assessment Battery (FAB), Digit Span Backward, and Rey’s word auditory verbal learning test (RVLT) immediate recall reached significant screening and diagnostic validity in predicting PD-MCI (AUC 0.705–0.795) with cutoff scores calculated by ROC analyses lying within normal range for normative data. Specific neuropsychological tests covering verbal memory, attention/set-shifting, and visual-spatial deficits are the best predictors of MCI in PD if valid cutoff scores are used. These results have consequences for cognitive diagnosis and potentially in establishing the rate of PD cognitive decline.     

Can clinical data predict progression to dementia in amnestic mild cognitive impairment?

BACKGROUND: To determine whether clinical data obtained by history and physical examination can predict eventual progression to dementia in a cohort of elderly people with mild cognitive impairment. METHODS: A prospective, longitudinal study of a cohort of elderly subjects with amnestic Mild Cognitive Impairment (MCI). Ninety subjects meeting the criteria for amnestic MCI were recruited and followed annually for an average of 3.3 years. Main outcome measure was the development of dementia determined by clinical assessment with confirmatory neuropsychological evaluation. RESULTS: Fifty patients (56%) developed dementia on follow-up. They were older, had lower Mini-mental status exam (MMSE) scores and a shorter duration of symptoms at the time of first assessment. Multivariate logistic regression analysis identified age at symptom onset as the only clinical parameter which distinguished the group that deteriorated to dementia from the group that did not. The odds ratio for age was 1.1 (confidence interval 1.04 - 1.18). CONCLUSIONS: Patients presenting with amnestic MCI insufficient for the diagnosis of dementia are at high risk of developing dementia on follow-up. In our cohort, 56% were diagnosed with dementia over an average period of 5.9 years from symptom onset. The only clinical predictor for the eventual development of dementia was older age at symptom onset. Clinical features alone were insufficient to predict development of dementia.     

Alcohol consumption in mild cognitive impairment and dementia: harmful or neuroprotective?

Objective: In several longitudinal studies, light‐to‐moderate drinking of alcoholic beverages has been proposed as being protective against the development of age‐related changes in cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia). However, contrasting findings also exist. Method: The English literature published in this area before September 2011 was evaluated, and information relating to the various factors that may impact upon the relationship between alcohol consumption and dementia or predementia syndromes is presented in the succeeding texts. Results: Light‐to‐moderate alcohol consumption may be associated with a reduced risk of incident overall dementia and AD; however, protective benefits afforded to vascular dementia, cognitive decline, and predementia syndromes are less clear. The equivocal findings may relate to many of the studies being limited to cross‐sectional designs, restrictions by age or gender, or incomplete ascertainment. Different outcomes, beverages, drinking patterns, and study follow‐up periods or possible interactions with other lifestyle‐related (e.g., smoking) or genetic factors (e.g., apolipoprotein E gene variation) may all contribute to the variability of findings. Conclusion: Protective effects of moderate alcohol consumption against cognitive decline are suggested to be more likely in the absence of the AD‐associated apolipoprotein E ε4 allele and where wine is the beverage. At present, there is no indication that light‐to‐moderate alcohol drinking would be harmful to cognition and dementia, and attempts to define what might be deemed beneficial levels of alcohol intake in terms of cognitive performance would be highly problematic and contentious. Copyright © 2012 John Wiley & Sons, Ltd.     

Does physical activity influence semantic memory activation in amnestic mild cognitive impairment?

The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P = 0.03), suggesting PA may enhance memory-related caudate activation in aMCI.