Alex Bahar-Fuchs

Factors Influencing Outcome After Orthopedic Trauma

BACKGROUND Some recent studies have suggested that certain types of orthopedic trauma result in ongoing disability and that factors other than injury severity or location may influence outcome. This study aimed to evaluate outcome 12 months and 2 years after severe orthopedic trauma, as measured on the Short Form (SF)-36 Health Survey, relative to a control group, to examine change over time and to examine which demographic, injury-related and psychological factors are associated with persisting disability. METHODS One hundred thirteen orthopedic trauma patients, recruited during rehabilitation, and 61 demographically similar uninjured controls were followed up at 1 and 2 years postinjury. Measures included the SF-36 Health Survey, Symptom Checklist-90-R, Brief Pain Inventory, Hospital Anxiety and Depression Scales, and Posttraumatic Stress Disorder Checklist-Specific. RESULTS Results indicated presence of significant ongoing disability in all SF-36 physical and mental health domains, significant ongoing psychologic adjustment problems, including posttraumatic stress disorder (PTSD) symptoms, and pain, with little or no improvement between 1 and 2 years postinjury. The presence of ongoing pain, anxiety, depression or PTSD symptoms were the strongest predictors of outcome on most variables, with older age also contributing to negative outcomes. Injury severity and type did not predict outcome, although those with lower limb fractures had greater pain and poorer physical outcomes that those with fractures in other locations. CONCLUSIONS This study has highlighted pain and PTSD symptoms as frequent and disabling factors after othropedic trauma. There is clearly a need to focus on alleviating these problems as part of the rehabilitation process.

Alcohol and drug use following traumatic brain injury: A prospective study

Primary objectives: To establish pre-morbid alcohol and drug use in persons with TBI, relative to controls, investigate how patterns of substance use change over time following TBI and identify factors associated with heavy post-injury substance use. Methods and procedures: The Alcohol Use Disorders Identification test (AUDIT) and Drug Abuse Screening Test (DAST) was completed by 121 hospital inpatients with TBI, documenting pre-injury alcohol and drug use, and 133 demographically similar controls. Participants with TBI completed these measures and the Hospital Anxiety and Depression Scale (HADS) again 1 and 2 years post-injury and 76 also completed them at 3 years. Results: Participants with TBI showed similar levels of drug and alcohol use to controls pre-injury, with 31.4% of the TBI group and 29.3% of controls drinking at hazardous levels. Alcohol and drug use declined in the first year post-injury, but increased by 2 years post-injury, with only 21.4% of participants with TBI reporting abstinence from alcohol and 25.4% drinking at hazardous levels. Only 9% showed a drug problem, but 24% had returned to some drug use. Those showing heavy alcohol use post-injury were young, male and heavy drinkers pre-injury. Drug and alcohol use was similar at 3 years post-injury. Conclusions: More active intervention is needed to reduce alcohol and drug use following TBI.

Cognitive training and cognitive rehabilitation for persons with mild to moderate dementia of the Alzheimer's or vascular type: a review.

Cognitive impairments, and particularly memory deficits, are a defining feature of the early stages of Alzheimers disease and vascular dementia. Interventions that target these cognitive deficits and the associated difficulties with activities of daily living are the subject of ever-growing interest. Cognitive training and cognitive rehabilitation are specific forms of non-pharmacological intervention to address cognitive and non-cognitive outcomes. The present review is an abridged version of a Cochrane Review and aims to systematically evaluate the evidence for these forms of intervention in people with mild Alzheimers disease or vascular dementia. Randomized controlled trials (RCTs), published in English, comparing cognitive rehabilitation or cognitive training interventions with control conditions and reporting relevant outcomes for the person with dementia or the family caregiver (or both), were considered for inclusion. Eleven RCTs reporting cognitive training interventions were included in the review. A large number of measures were used in the different studies, and meta-analysis could be conducted for several primary and secondary outcomes of interest. Several outcomes were not measured in any of the studies. Overall estimates of the treatment effect were calculated by using a fixed-effects model, and statistical heterogeneity was measured by using a standard chi-squared statistic. One RCT of cognitive rehabilitation was identified, allowing the examination of effect sizes, but no meta-analysis could be conducted. Cognitive training was not associated with positive or negative effects in relation to any of the reported outcomes. The overall quality of the trials was low to moderate. The single RCT of cognitive rehabilitation found promising results in relation to some patient and caregiver outcomes and was generally of high quality. The available evidence regarding cognitive training remains limited, and the quality of the evidence needs to improve. However, there is still no indication of any significant benefits from cognitive training. Trial reports indicate that some gains resulting from intervention may not be captured adequately by available standardized outcome measures. The results of the single RCT of cognitive rehabilitation show promise but are preliminary in nature. Further well-designed studies of cognitive training and cognitive rehabilitation are required to provide more definitive evidence. Researchers should describe and classify their interventions appropriately by using the available terminology.

Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study

Background We assessed the clinical utility of β-amyloid (Aβ) imaging with 18F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimers disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time. Methods 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <−1.5. Results At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB−, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB− developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB− had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−. Conclusions 18F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline. Trial registration number NCT01138111.

Olfactory deficits and amyloid-β burden in Alzheimer's disease, mild cognitive impairment, and healthy aging: a PiB PET study.

Olfactory deficits and increased amyloid-β (Aβ) burden are observed in people with amnestic mild cognitive impairment (aMCI); both factors may be predictive of Alzheimers disease (AD). We explored whether olfactory identification is related to in vivo measures of Aβ burden using Pittsburgh Compound B (PiB) PET. Nineteen control, 24 aMCI, and 20 AD participants completed an olfactory identification task and underwent PiB PET scanning. Control participants performed better on olfactory identification and showed lower PiB binding than aMCI patients. There was a significant correlation between both factors when pooling all groups together but not when considering each group separately. In addition, the olfactory identification score did not differ between aMCI participants who were PiB-positive and those who were PiB-negative. We conclude that AD-related olfactory identification deficits are not directly related to Aβ burden.

Awareness of olfactory deficits in healthy aging, amnestic mild cognitive impairment and Alzheimer's disease.

BACKGROUND Olfactory dysfunction is present in early Alzheimers disease (AD), and has now been reported in people with amnestic mild cognitive impairment (aMCI). Recent evidence suggests that unawareness of an olfactory deficit may predict which MCI patients will subsequently meet AD criteria. However, important methodological limitations challenge this suggestion. While addressing some of the limitations of previous research, this preliminary study explores unawareness of olfactory deficits as a predictive factor of future AD among people with aMCI. METHODS Twenty-five participants with aMCI, 25 AD patients, and 22 healthy elderly participants underwent testing of olfactory identification. Subjective reports regarding perceived decline in olfactory detection and olfactory identification were also obtained. A subset of participants was reassessed 12 months later. RESULTS Control participants performed better than both aMCI and AD patients on olfactory identification. Almost uniformly, participants did not report decline in either olfactory detection or identification. Prediction of olfactory identification scores from subjective reports of olfactory function was poor, and awareness of olfactory decline bore no relationship to the likelihood of aMCI patients progressing to AD by the 12-month review. CONCLUSIONS Treating awareness of olfactory function as a unitary construct can be misleading, and there is a poor relationship between subjective and objective measures of olfactory ability. Our preliminary data suggest that unawareness of olfactory decline does not improve the identification of patients with MCI who are more likely to be in the prodromal phase of AD. Replication in a larger cohort is needed to support these findings.

18F-florbetaben Aβ imaging in mild cognitive impairment

Introduction18F-florbetaben and positron emission tomography were used to examine the relationships between β-amyloid (Aβ) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impairment (MCI).MethodsForty-five MCI participants were evaluated. A neocortical standardized uptake value ratio threshold ≥ 1.45 was used to discriminate high from low Aβ burden. Correlations were adjusted for age, gender and years of education.ResultsHigh Aβ burden was found in 53% of MCI. Regression analyses showed standardized uptake value ratio (r = -0.51, P = 0.0015) and hippocampal volume (r = 0.60, P = 0.024) both contributing to episodic memory impairment in independent fashion. White matter hyperintensities correlated with nonmemory cognition, and this correlation was particularly associated with Aβ burden.ConclusionHigher Aβ deposition in MCI is associated with more severe memory impairment and is contributing to early amnestic symptoms independent of hippocampal atrophy.

Olfactory Performance in AD, aMCI, and Healthy Ageing: A Unirhinal Approach

Olfactory dysfunction constitutes one of the earliest signs of Alzheimers disease (AD) and has been shown in individuals with amnestic mild cognitive impairment (aMCI). Whether the severity of olfactory impairments in aMCI patients parallels those in AD has not been clearly established. In addition, given reports of asymmetries in neuropathological burden in early AD, functional asymmetries in olfactory performance may enhance early detection if olfactory function is assessed unirhinally. We compared AD, aMCI, and healthy participants on olfactory identification and memory assessed unirhinally. Olfactory identification was most proficient in the healthy participants and least proficient in AD, although this disparity did not depend on nostril side. Nevertheless, when only the worst nostril of each participant was included in the analysis, aMCI patients outperformed their AD counterparts. In contrast, when only the best nostril of each participant was included in the analysis--often regarded as an estimate of birhinal performance--this difference between aMCI and AD dissipated. Olfactory memory did not differ significantly across the groups, perhaps reflecting a floor effect. The findings support the hypothesis that unirhinal olfactory assessment may assist in differentiating between demented and nondemented individuals.

Prediction of Amyloid-β Pathology in Amnestic Mild Cognitive Impairment with Neuropsychological Tests

Assessment of disease biomarkers, particularly the in vivo assessment of amyloid-β (Aβ) burden with positron emission tomography (PET), is gradually becoming central to the diagnosis of mild cognitive impairment (MCI) due to Alzheimers disease (AD). However, the incorporation of biomarker evidence to the diagnostic process is currently restricted mainly to research settings. The identification of memory measures that are associated with Aβ is of clinical relevance as this may enhance the confidence in making a diagnosis of MCI due to AD in clinical settings. Forty one persons with amnestic MCI underwent Aβ imaging with (18)F-Florbetaben PET, magnetic resonance imaging, and a comprehensive neuropsychological assessment. All measures of episodic memory were significantly correlated with Aβ burden, but regression analyses revealed a strong and selective association between story recall and Aβ over and beyond the effects of age, education, global cognition, hippocampal volume, or other memory tests. Analyses of sensitivity and specificity of memory measures to detect high versus low Aβ scans suggested that word-list recall performed better when high sensitivity was preferred, whereas story recall performed better when high specificity was preferred. In conclusion, a measure of story recall may increase the confidence in making a diagnosis of MCI due to AD in clinical settings.

A 12-week multidomain intervention versus active control to reduce risk of Alzheimer’s disease: study protocol for a randomized controlled trial

BackgroundDisappointing results from clinical trials of disease-modifying interventions for Alzheimer’s dementia (AD), along with reliable identification of modifiable risk factors in mid life from epidemiological studies, have contributed to calls to invest in risk-reduction interventions. It is also well known that AD-related pathological processes begin more than a decade before the development of clinical signs. These observations suggest that lifestyle interventions might be most effective when targeting non-symptomatic adults at risk of AD. To date, however, the few dementia risk-reduction programs available have targeted individual risk factors and/or were restricted to clinical settings. The current study describes the development of an evidence-based, theoretically-driven multidomain intervention to reduce AD risk in adults at risk.MethodThe design of Body Brain Life (BBL) is a randomized controlled trial (RCT) to evaluate a 12-week online AD risk-reduction intervention. Eligible participants with several modifiable risk factors on the Australian National University (ANU) AD Risk Index (ANU-ADRI) are randomly allocated to an online only group, an online and face-to-face group, or an active control group. We aim to recruit 180 participants, to undergo a comprehensive cognitive and physical assessment at baseline, post-intervention, and 6-month follow-up assessment. The intervention comprises seven online modules (dementia literacy, risk factor education, engagement in physical, social, and cognitive lifestyles, nutrition, and health monitoring) designed using contemporary models of health behavior change.DiscussionThe BBL program is a novel online intervention to reduce the risk of AD in middle-aged adults at risk. The trial is currently under way. It is hypothesized that participants in the intervention arms will make lifestyle changes in several domains, and that this will lead to a reduction in their AD risk profile. We also expect to show that health behavior change is underpinned by changes in psychological determinants of behavior. If successful, the findings will contribute to the development of further dementia risk reduction interventions, and thus contribute to the urgent need to lower dementia risk factors in the population to alter future projections of disease prevalence. Longer follow-up of BBL participants and replications using large samples are required to examine whether reduction in AD risk factors will be associated with reduced prevalence.Trial registrationReg. no. ACTRN12612000147886