Relationship between Walking and Driving, and Cognitive Functioning Common to Both Modes of Mobility, in Healthy Older Adults.

INTRODUCTION: Driving and walking, the two main modes of mobility, require numerous common skills in the motor, sensory, and cognitive domains that deteriorate with age. The objective of this study was to investigate the relationship between walking and driving in healthy older drivers and to determine whether certain cognitive processes are involved in both modes of mobility. METHOD: Seventy-six older drivers from the Safe Move cohort were assessed in the following three domains: (1) cognition, using parts A and B of the Trail Making Test (TMT), the digit symbol substitution test (DSST), the Stroop test, and the Digit span; (2) gait, using a dual-task (DT) paradigm with a counting task; and (3) driving, assessed via a 40-50 min on-road test. Analyses were also performed on 2 subgroups: young-old (70-74 years old; n = 43) and old-old (≥75 years; n = 33). RESULTS: Four significant correlations were found across the whole sample between gait performance under DT conditions and driving scores. One correlation was also found in old-old adults. None were found in young-old adults. Furthermore, several cognitive measures were significantly correlated to both modes of mobility: TMT-A and B completion time in the whole sample, and DSST performance in the whole sample and old-old adults. DISCUSSION/CONCLUSION: Walking in complex conditions and on-road driving performance are closely related in healthy older drivers. Visuospatial attention, processing speed, and executive function are crucial and common cognitive processes to both modes of mobility in this population. Impairment in these cognitive functions should thus alert health professionals as it can quickly lead to mobility disorders, loss of autonomy and social isolation. Developing specific preventive programs and mobility support systems for healthy older adults is also crucial.

Bone, cognitive, and anthropometric profiles and their relation to fracture sites in fallers: a cross-sectional study.

Risk factors involved in the different osteoporotic fracture locations are not well-known. The results of this study suggest that there is not one typical profile characterising a particular fracture site but that the occurrence of a fracture may result from the combination of different bone, cognitive, and anthropometrics characteristics. PURPOSE: Risk factors involved in the different osteoporotic fracture locations are not well-known. The aim of this study was to identify the differences in bone, cognitive, and anthropometric characteristics between different fracture sites, and to determine whether the site of a fall-related fracture is related to a specific profile. METHODS: One hundred six women aged 55 years and older with a recent fall-related fracture of the hip (n = 30), humerus (n = 28), wrist (n = 32), or ankle (n = 16) were included. Bone, cognitive, and anthropometric characteristics were first compared among the four fracture site groups. Then, a principal component analysis (PCA) was performed and a comparison was made between the four profiles identified by the first two PCA components. RESULTS: The four fracture site groups differed significantly in their education level, bone mineral density (BMD), body mass index (BMI), fear of falling, and number of errors in the Trail Making Test B, an executive function test. Each of the four fracture sites was found in each four PCA profiles, albeit with a different distribution. The profiles differed mainly by bone, cognitive, and anthropometric characteristics, but also by fear of falling. CONCLUSIONS: The fall-related fracture sites differ significantly in anthropometric and bone parameters, in fear of falling and in cognitive abilities. There is not one typical bone, cognitive, and anthropometric profile characterising a particular fall-related site, but rather several possible profiles for a given site. This suggests that the fracture site depends on a combination of several characteristics of the patient.

Reduced gait and postural stability under challenging conditions in fallers with upper limb fracture.

BACKGROUND: While most fractures are caused by falls, not all falls result in fractures. Risk factors for falls are well established, but only weak associations have been demonstrated for risk factors for fractures. Conflicting results on the implication of bone mineral density (BMD) suggest that other risk factors should be studied, such as gait and balance disorders. AIMS: Gait and postural stability in challenging conditions were, therefore, compared between fallers with and without fracture. METHODS: We enrolled 80 adults aged 55 and older who fell in the previous year. We compared gait and posture after obstacle crossing between fallers with an upper-limb fracture (n = 38), and fallers without fracture (n = 42). Data on BMD, body mass index, handgrip strength, fear of falling, number of comorbidities, number of falls, global cognition, executive functioning and education level were collected. RESULTS: Compared to fallers without fracture, fallers with fracture had significant lower gait velocity (Likelihood-Ratio = 4.93; P = 0.03) and lower postural stability during stabilization after obstacle crossing (Likelihood-Ratio = 10.99; P < 0.001). In addition, fallers with fracture had lower handgrip strength (Likelihood-Ratio = 9.92; P = 0.002), lower education level (Likelihood-Ratio = 8.32; P = 0.004), poorer executive functions (Likelihood-Ratio = 5.81; P = 0.02, higher fear of falling (Likelihood-Ratio = 5.55; P = 0.02) and were more likely women (Likelihood-Ratio = 17.55; P < 0.001), compared to fallers without fracture. DISCUSSION: This study demonstrated that the main difference between fallers with upper-limb fracture and fallers without fracture is mobility in dynamic condition. Poor executive function and low muscular strength could also be involved. CONCLUSIONS: These factors should be taken into account when assessing risk factors for fracture and implementing preventive programs. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. NCT02292316.

Identification of the human medial temporal lobe regions on magnetic resonance images.

The medial temporal lobe (MTL) plays a key role in learning, memory, spatial navigation, emotion, and social behavior. The improvement of noninvasive neuroimaging techniques, especially magnetic resonance imaging, has increased the knowledge about this region and its involvement in cognitive functions and behavior in healthy subjects and in patients with various neuropsychiatric and neurodegenerative disorders. However, cytoarchitectonic boundaries are not visible on magnetic resonance images (MRI), which makes it difficult to identify precisely the different parts of the MTL (hippocampus, amygdala, temporopolar, perirhinal, entorhinal, and posterior parahippocampal cortices) with imaging techniques, and thus to determine their involvement in normal and pathological functions. Our aim in this study was to define neuroanatomical landmarks visible on MRI, which can facilitate the examination of this region. We examined the boundaries of the MTL regions in 50 post-mortem brains. In eight cases, we also obtained post-mortem MRI on which the MTL boundaries were compared with histological examination before applying them to 26 in vivo MRI of healthy adults. We then defined the most relevant neuroanatomical landmarks that set the rostro-caudal limits of the MTL structures, and we describe a protocol to identify each of these structures on coronal T1-weighted MRI. This will help the structural and functional imaging investigations of the MTL in various neuropsychiatric and neurodegenerative disorders affecting this region.

A Dual-Task Paradigm Combining Physical and Cognitive Training in Mice: Application to Aging.

Physical Activity (PA) is often associated with better overall health status, especially in older adults. Numerous pieces of evidence indicate that PA would be more beneficial when applied in conjunction with Cognitive Training (CT) either simultaneously (i.e., in Dual-Task [DT]) or sequentially. Nonetheless, the underlying mechanisms of such benefits remain elusive. To help delve deeper into their understanding, we developed a cognitive-motor DT paradigm in young adult mice and subsequently tested its effect in old age. Three groups of young adults C57BL/6J mice (3.5 months of age; n=10/group) were required. They were given cognitive tasks, either alone (Control) or in combination with PA which was administered either sequentially (SeqT group) or simultaneously (DT group). Mice were trained in a touchscreen chamber: first on a Visual Discrimination (VD) learning task, then on its Reversal (RVD) which assesses cognitive flexibility alongside procedural learning. PA was given through a homemade treadmill, designed to fit in the touchscreen chambers and set at 9 m/min. Fourteen months later, we further evaluated the effects of PA administered in both DT and SeqT groups, on the performance of the now 19-month-old mice. When compared to SeqT and control groups, DT mice significantly displayed better procedural learning in both VD and RVD tasks as young adults. In the RVD task, this enhanced performance was associated with both poorer inhibition and motor performance. Finally, in 19-month-old mice, both DT and SeqT mice displayed better motor and cognitive performances than control mice. This new cognitive-motor DT paradigm in mice yields an interesting framework that should be useful for adapting DT training in aging, including providing knowledge on the neurobiological correlates, to get the most out of its benefits.

The PAPA Questionnaire: Assessment of Long-Term Engagement in Activities, with Separate Quantification of Their Physical, Cognitive, and Social Components.

Purpose: Engagement in activities promotes healthy living. Evaluating it is a challenging issue. Assessing engagement in activities while differentiating the physical, cognitive, and social component of each activity and taking into account the intensity level involved in each of the three components would be very relevant. Since none of the currently available cognitive reserve and questionnaires on the activities practiced takes into consideration both points, the purpose of this new questionnaire, called Pertinent Activities Practice in Adults (PAPA) questionnaire, is to fill these gaps. Patients and Methods: The questionnaire was developed through a literature review and interviews with older adults (n=177 ≥55 years). The intensity level of each item (none, light, moderate, or high) was determined by the compendium of physical activities for the physical component and consensus for the cognitive and social components, then validated by 56 professional experts (6 groups: physiotherapists, neuropsychologists, occupational therapists, geriatricians, etc.). Results: The PAPA questionnaire includes 75 items that give rise to 4 scores (sedentary lifestyle and physical, cognitive, and social activity scores) weighted by the frequency, duration, and intensity level for each component. The weighted percentage of agreement of the expert groups for the intensity levels was never significantly lower than the minimum target threshold (80% of the hypothetical median) except in a single domain (cognitive) for an expert group non-specialized in cognition. Cronbach's alpha was ≥0.85. Conclusion: This questionnaire, which assesses long-term engagement in activities, with separate quantification of the physical, cognitive, and social components of a wide range of activities, should help guide actions to promote healthy aging and reduce dementia risk.

Gripwise Versus Jamar: The Challenge of a New Dynamometer Assessing Handgrip Strength.

BACKGROUND: Sarcopenia diagnosis is partly based on handgrip strength (HGS) assessment. The gold-standard dynamometer for this measurement is the Jamar. The electronic Gripwise is a smaller and lighter one, and its measurements are correlated with the Jamar's in laboratory tests. Our study aimed to confirm this correlation in aged patients. METHODS: This monocenter cross-sectional study was performed in patients of 65 years and older admitted at the University Hospital. Participants were assessed either in a seated or bedridden position, randomly allocated to begin the measurements with the Jamar or the Gripwise. RESULTS: Among 649 aged inpatients assessed for eligibility, 348 were included (mean age: 79 ±â€…9; 52% females). The intraclass correlation coefficient was 0.93 (95% confidence interval [CI] 0.92-0.94, p < .001) for the maximum value measured with both devices and 0.94 (95% CI 0.93-0.95, p < .001) for the mean values. However, there was a significant difference in detecting low values (<16 kg in women, <27 kg in men), found in 48% of patients with Jamar, and 71% with Gripwise (p < .001). Thus, we determined alternate cutoffs for diagnosing HGS low values with the Gripwise (<12 kg in women, <22 kg in men), further validated in a supplementary validation population (n = 70). The diagnostic performances of these alternative cutoffs were high (93% sensitivity and 87% specificity in women; 94% sensitivity and 96% specificity in men). CONCLUSIONS: The correlation of the Gripwise with the Jamar was confirmed in aged inpatients. However, lower values recorded with the Gripwise require alternate cutoffs for a relevant low HGS diagnosis.

Barriers and facilitators to social participation after driving cessation among older adults: A cohort study.

BACKGROUND: Driving cessation is a challenging transition for older drivers. It is indeed often associated with reduced mobility, loss of autonomy and poor quality of life, as in individuals with acquired disabilities. We examined factors that inhibit or facilitate out-of-home occupations after driving cessation (shopping, visiting/helping friends/family, leisure, and associative activities) in older adults, with particular focus on the role of anticipation. METHODS: This longitudinal study was conducted with the SAFE MOVE cohort (n=1014 drivers aged≥70 years). Socio-demographic, health, cognitive, mobility and out-of-home occupations data were collected at home at baseline and by a postal questionnaire at 2-year follow-up. RESULTS: In total, 48 (5%) participants stopped driving between baseline and follow-up, at a mean age of 81.8 years; 71% of drivers who stopped reported that driving cessation affected their out-of-home occupations. Participation in social occupations started to decline before driving cessation. Retired drivers were older, had poorer health, poorer cognitive abilities, drove less at baseline but used more public transportation than active drivers. As compared with participants who did not consider driving cessation at baseline, those who did were more likely to expect a better quality of life in the event of driving cessation and to use public transportation at baseline and follow-up despite their older age and poorer health. CONCLUSION: Some factors associated with reduced social participation and driving cessation are inevitable, such as health status. However, other factors may facilitate maintenance of social participation, including anticipation of driving cessation and mobility habits. Our findings highlight the need for appropriate interventions that are widely available to older drivers before driving cessation occurs and for public policy actions facilitating alternative transport systems.

Relationships Between Cognitive and Driving Self-awareness in Older Drivers.

OBJECTIVES: Many older drivers incorrectly estimate their driving ability. The present study aimed to determine whether, and if so, to what extent unawareness of cognitive abilities affects self-awareness of driving ability. METHOD: Two successive studies were conducted in older drivers. A cohort study investigated cognitive self-awareness and an experimental study examined driving self-awareness. In each one, self-awareness was assessed by cross-analyzing objective (respectively Trail-Making Tests A and B and the Digit Symbol Substitution Test and driving performance of on-road assessment) and subjective data (responses about everyday cognitive skills and driving ability). Older drivers were then classified as being over-, correct, or underestimators. The 3 cognitive and driving self-awareness profiles were then cross-analyzed. RESULTS: In the cohort study, 1,190 drivers aged 70 years or older were included. The results showed that 42.7% of older drivers overestimated their cognitive ability, 42.2% estimated it correctly, and 15.1% underestimated it. The experimental study included 145 participants from the cohort. The results showed that 34% of participants overestimated, 45% correctly estimated, and 21% underestimated their driving ability. There was a significant relationship between cognitive and driving self-awareness profiles (p = .02). This overlap was more marked in overestimators. DISCUSSION: Significant overlap between cognitive and driving self-awareness provides useful and new knowledge about driving in the aging population. Misestimation of cognitive ability could hamper self-awareness of driving ability, and consequently self-regulation of driving. It is now crucial to develop measures that promote self-awareness of ability.

Effects of chronic tramadol administration on cognitive flexibility in mice.

RATIONALE: Tramadol is widely used for pain relief especially in seniors. However, long-term use of tramadol has serious adverse effects, including cognitive impairment. Besides its memory effects, already demonstrated in animals, a recent clinical report suggests that tramadol could also affect executive function in seniors. Several studies have hypothesized that the anti-muscarinic properties of tramadol could be responsible for the deleterious effects of tramadol on cognition. OBJECTIVES: We aimed at investigating the effects of chronic administration of tramadol on cognitive flexibility in adult male mice, as assessed by a visual discrimination reversal task using a touchscreen device. The effects of tramadol were further compared to those of scopolamine, a reference muscarinic antagonist. RESULTS: We found that, during the early phase of the reversal task, when cognitive flexibility is most in demand, both tramadol-treated mice (20 mg/kg, s.c., twice a day) and scopolamine-treated mice (0.5 mg/kg, s.c., twice a day) needed more correction trials and showed a higher perseveration index than saline-treated mice. Therefore, tramadol affects cognitive flexibility, and its anticholinergic properties could be at least partly involved in these deficits. CONCLUSIONS: In view of these deleterious cognitive effects of tramadol, physicians should be cautious when prescribing this analgesic, especially in seniors who are more vulnerable to adverse drug events and in which alternative prescription should be preferred whenever possible.

Adverse Effects of Anticholinergic Drugs on Cognition and Mobility: Cutoff for Impairment in a Cross-Sectional Study in Young-Old and Old-Old Adults.

BACKGROUND: Drugs with anticholinergic properties are commonly prescribed in older adults despite growing evidence of their adverse outcomes. Several issues regarding these detrimental effects remain unresolved, such as the putative existence of a threshold above which anticholinergic drug consumption impairs cognitive or mobility performance. OBJECTIVES: We aimed to investigate the number of anticholinergic drugs and the anticholinergic burden that leads to mobility or cognitive impairment and compare the effects in community-dwelling older adults in two age groups ("young-old" 55-74 vs. "old-old" ≥ 75 years). METHODS: In a cross-sectional study, we identified drugs with anticholinergic (antimuscarinic) properties using the Anticholinergic Drug Scale. Cognition was assessed using the Mini Mental State Examination (MMSE) and the Trail Making Test (TMT-A and TMT-B), and mobility was assessed using the Timed Up and Go (TUG) test. RESULTS: The study population consisted of 177 volunteers, 114 of whom were classed as young-old and 63 were classed as old-old adults. Despite the lack of cutoff values for impaired outcomes in young-old adults, impaired MMSE were significantly more numerous in users than in nonusers of anticholinergic drugs. In old-old adults, receiver operating characteristic (ROC) curve analysis indicated that taking a single anticholinergic drug per day was associated with impaired TMT-B completion time, TMT difference score (B-A), and TUG scores. The cutoff for anticholinergic burden was also one for these same outcomes. Based on these cutoff values, multivariate logistic regressions in old-old adults showed that the increased risk of impaired cognition and mobility was independent of confounding factors, including comorbidities. They also suggested that anticholinergic drugs would affect mobility through executive functions. CONCLUSIONS: Drugs with anticholinergic (antimuscarinic) properties are associated with cognitive impairment in individuals as young as 55 years, and only one such drug per day, regardless of its anticholinergic burden, is associated with both impaired cognition and impaired mobility in old-old adults. Therefore, wherever possible, clinicians should avoid prescribing drugs with anticholinergic properties.

Psychotropic Polypharmacy in Adults 55 Years or Older: A Risk for Impaired Global Cognition, Executive Function, and Mobility.

OBJECTIVES: With their broad spectrum of action, psychotropic drugs are among the most common medications prescribed to the elderly. Consequently, the number of older adults taking multiple psychotropic drugs has more than doubled over the last decade. To improve knowledge about the deleterious effects of psychotropic polypharmacy, we investigated whether there is a threshold number of psychotropic molecules that could lead to impairment of global cognition, executive function, or mobility. Furthermore, relationships between the number of psychotropic molecules and cognitive and mobility impairment were examined. DESIGN: Cross-sectional study. SETTING: University Hospital of Caen (France) and advertisements in medical offices. PARTICIPANTS: Community-dwelling older adults 55 years and older (n = 177; 69.8 ± 9.3 years; 81% women). MEASUREMENTS: Number of psychotropic molecules taken daily, global cognition assessed with the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), processing speed with the Trail Making Test (TMT) A, executive function with the TMT B and TMT B-A, and mobility with the Time Up and Go (TUG). The threshold numbers of psychotropic molecules were determined by ROC curves analysis. Based on these threshold values, multinomial logistic regression adjusting for covariates was then performed. RESULTS: Logistic regressions showed that the threshold of two daily psychotropic molecules, identified by the ROC curves analysis, increases the risk of impaired executive function (p = .05 and.005 for the TMT B and TMT B-A, respectively), global cognition (p = .006 and.001 for the MMSE and MoCA, respectively), and mobility (p = .005 for the TUG), independent of confounding factors, including comorbidities. Furthermore, psychotropic polypharmacy would affect mobility through executive functions. CONCLUSION: Impairment of global cognition, executive function, and mobility when as few as two psychotropic molecules are consumed in relatively healthy young older adults should alert physicians when prescribing combinations of psychotropic medications.

Functional imaging of working memory in Parkinson's disease: compensations and deficits.

BACKGROUND AND PURPOSE: Over and above typical motor alterations, executive and working memory (WM) impairment can also occur in early idiopathic Parkinson's disease (PD). We aimed to investigate the compensatory neural processes involved in WM performance, as well as the networks involved in the long-term memory transfer from short-term stores in PD. METHODS: Relative cerebral blood flow (rCBF) was mapped with H2O(15)-PET in eight treated nondemented PD patients while performing a WM verbal double-task (Brown-Peterson paradigm) using both short (6-second) and long (18-second) delays. RESULTS: As compared to nine age-matched healthy subjects, performance of the PD group was only slightly reduced on the short-delay but markedly impaired on the long-delay task. Underlying the relatively preserved short-delay performance, the PD group exhibited overactivation of prefrontal and parietal areas involved in attention-demanding processes, suggestive of efficient compensatory processes. Further supporting this, significant positive correlations were found between short-delay performance and rCBF in the bilateral inferior parietal cortex. In contrast, the lack of overactivation with the long-delay task together with posterior cingulate hypoactivation would support the idea of functional disconnection impairing transfer of information from prefrontal onto (para)limbic areas. These findings suggest novel areas of investigation into early cognitive impairments in PD.

Self-awareness and the medial temporal lobe in neurodegenerative diseases.

Accurate self-awareness is essential for adapting one's behaviour to one's actual abilities, to avoid risky behaviour. Impaired self-awareness of deficits is common in neurodegenerative diseases. Numerous studies show an involvement of midline cortical areas in impaired self-awareness. Among the other brain regions implicated stand the medial temporal lobe (MTL) structures (i.e. hippocampus, amygdala, and temporopolar, entorhinal, perirhinal and posterior parahippocampal cortices). This review aims at evaluating the role of those structures in self-awareness in neurodegenerative diseases. To this aim, we briefly review impaired self-awareness in neurodegenerative diseases, give a neuroanatomical background on the MTL structures, and report those identified in neuroimaging studies on self-awareness. The MTL shows neuropathological, and structural or functional changes in patients who overestimate their abilities in the cognitive, socio-emotional or daily life activities domains. The structures implicated differ depending on the domain considered, suggesting a modality-specific involvement. The functional significance of the findings is discussed in view of the neuroanatomical networks of the MTL and in the context of theoretical models of self-awareness.

Imaging visual recognition memory network by PET in the baboon: perirhinal cortex heterogeneity and plasticity after perirhinal lesion.

We recently mapped the visual recognition memory network in the behaving baboon using a positron emission tomography (PET) activation paradigm with 18F-fluoro-deoxyglucose during a visual delayed matching-to-sample task. This study confirmed the key role of the perirhinal cortex and documented an unexpected left-sided advantage. Specific contribution of each subdivision of the perirhinal cortex has, however, never been investigated. Furthermore, although alteration to the perirhinal cortex has been implicated in several brain disorders, putative plasticity within the entire brain network after perirhinal damage remains largely unknown. To confirm our previous data and to investigate these latter issues, we used our PET activation paradigm on a second healthy baboon before and after 16 months after bilateral excitotoxic lesions of the perirhinal cortex. Activation common to our two healthy baboons occurred only in the left rostroventral perirhinal cortex (i.e., areas 36pm and rostral 36r) and insular cortex. Although histologic analysis disclosed that the perirhinal lesions achieved in the present baboon were essentially caudal to this preoperatively activated area, memory performance was severely impaired. Concomitant with this long-lasting cognitive deficit, changes in the neural network implicated in the task were observed, involving disappearance of the preoperative activations and appearance of a significant activation of the frontal and occipital cortices. However, different activation patterns were found in the first and last eight postoperative months. These findings highlight the functional heterogeneity of the perirhinal cortex and evidence progressive plasticity after perirhinal cortex damage.

Polypharmacy Cut-Off for Gait and Cognitive Impairments.

BACKGROUND: Polypharmacy is a well-established risk factor for falls, and these are one of the major health problems that affect the quality of life as people age. However, the risk of mobility and cognitive impairments consecutive to polypharmacy has been little addressed, despite the association between these adverse outcomes and falls. Moreover, the rare polypharmacy cut-offs were all but one arbitrarily determined. OBJECTIVE: Studying relationships between polypharmacy and both mobility and cognitive impairments, and statistically determining a cut-off point in the number of medicinal molecule beyond which polypharmacy has deleterious consequences with respect to mobility and cognitive impairment. METHODS: We enrolled 113 community-dwelling adults aged 55 years and older with a fall history, with or without injury, in the previous year. We carefully collected information about daily medicinal molecules taken. We assessed basic mobility and global cognition with the Time-Up-and-Go and the Montreal Cognitive Assessment (MoCA) test, respectively (clinicaltrials.gov NCT02292316). RESULTS: Timed-Up and Go test and MoCA scores were both significantly correlated with the number of molecule, used. Receiver Operating Characteristic curves indicate, with high prediction (p < 0.002), that daily consumption of five or more molecules is associated with risk for both impaired mobility and global cognition. These relationships were independent of the number of comorbidities and of the pharmacological class. CONCLUSION: Community-dwelling adults aged 55 years and older who take five or more daily medicinal molecules are at high risk for both mobility and cognitive impairments. Physicians and patients should be aware of these new findings, especially when there are multiple prescribers involved in the care of the patient.

Correlations between visual recognition memory and neocortical and hippocampal glucose metabolism after bilateral rhinal cortex lesions in the baboon: implications for Alzheimer's disease.

In Alzheimer's disease (AD), the rhinal cortex is the area earliest and most affected by neurofibrillary tangles, and the degree of temporoparietal glucose hypometabolism and rhinal cortex atrophy are both correlated with dementia severity. In monkeys, damage to the rhinal cortex leads to severe impairment in declarative memory, which is also affected preferentially in early AD. To investigate the contribution of rhinal alterations to the interrelationships between cerebral hypometabolism and declarative memory impairment observed in AD, we studied the effects of excitotoxic bilateral rhinal lesions in baboons on cerebral glucose consumption (CMRglc) as measured by positron emission tomography and performance on a visual recognition memory task as assessed in parallel by a delayed nonmatching-to-sample task. We reported previously that these rhinal lesions induce both a long-lasting hypometabolism in several remote brain regions (Meguro et al., 1999) and impaired memory performance (Chavoix et al., 2002). The present analysis indicates that across lesioned and sham baboons, memory scores were significantly positively correlated (p < 0.05; Spearman) with concomitant CMRglc values of several brain areas, such as neocortical associative and posterior hippocampal regions. These findings, reminiscent of those reported in AD, suggest that the neurodegenerative process that affects the rhinal cortex in early AD plays a crucial role in the pattern of brain hypometabolism and consequently in the declarative memory impairments characteristic of this disease.

Multiple Object Tracking While Walking: Similarities and Differences Between Young, Young-Old, and Old-Old Adults.

OBJECTIVE: Walking while simultaneously engaged in another activity becomes more difficult as one grows older. Here, we address the issue of changes in dual-task behavior at different stages of life, particularly in the latter stages. METHODS: We developed a dual task that combined walking along an 8-m walkway with a multiple object tracking (MOT) task of increasing difficulty. This secondary cognitive task imitates visuospatial daily activities and provides reliable quantitative measurements. Our dual-task paradigm was tested on 27 young adults (23.85 ± 2.09 years old) and two groups of older adults (18 young-old and 18 old-old adults, aged 63.89 ± 3.32 and 80.83 ± 3.84 years, respectively). RESULTS: Significant decrease in tracking performance with increasing complexity of the MOT task was found in all three groups. An age-related decrease in MOT and gait performance was also found. However, young-old adults performed as well as young adults under low attentional load conditions (in the MOT task and simple walking), whereas their performance was as impaired as those of old-old adults under high attentional load conditions (in the MOT task and walking under dual-task condition). DISCUSSION: These different profiles between the two groups of older participants could be explained in terms of compensation strategies and risk of falling.

Brain glucose hypometabolism after perirhinal lesions in baboons: implications for Alzheimer disease and aging.

The authors previously reported that excitotoxic lesions of both the perirhinal and entorhinal cortices in baboons induce remote neocortical and hippocampal hypometabolism reminiscent of that observed in Alzheimer disease (AD), suggesting that disconnection may play a role in AD. Because the cerebral metabolic rate of glucose (CMR ) was preferentially correlated with perirhinal damage, the area first affected by neurofibrillary tangles in both AD and normal aging, the present series of experiments aimed at assessing the specific metabolic effects of perirhinal lesions. Using PET, CMR was measured before surgery and sequentially over the ensuing 10 months. Compared with sham-operated baboons, perirhinal lesions induced significant-albeit late and transient-CMR decreases in several brain regions, which significantly correlated with histologic damage for some of these regions. Among them, the temporal and hippocampal regions are metabolically affected after extensive rhinal lesions, in early AD, and aging, while the prefrontal region is affected in aging only. Furthermore, in contrast to AD and rhinal lesions, the posterior cingulate cortex was spared. Both the progressive but significant metabolic effects and specific hypometabolic pattern after perirhinal lesions were confirmed by direct comparisons with previous data obtained after combined lesions of both rhinal areas. Thus, although perirhinal damage appears in itself insufficient to induce sustained CMR decreases, it may contribute to the hypometabolic profile of both AD and normal aging, most likely with a stronger contribution in the latter.

Interference between walking and a cognitive task is increased in patients with bilateral vestibular loss.

The aim of this study was to determine whether there is more deterioration in walking under dual-task conditions in patients with bilateral vestibular loss (BVL) than in healthy subjects, as opposed to the findings after unilateral loss. For this purpose, 12 patients with BLV and 12 healthy control subjects performed 3 tasks: walking along a 10-m walkway, counting backwards by two, and both tasks simultaneously. Patients did not differ from controls in their walking speed in the single task condition, or in their cognitive performance in both the single and dual-task conditions. However, walking performance was more affected in patients than in controls under dual-task conditions, as shown by slower gait speed in the dual-task, higher reduction in gait speed from single to dual-task, and lower global dual-score. These findings provide evidence for greater attentional interference between walking and counting in patients with BVL.