Hélène Imbeault

Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer's Disease Dementia

BACKGROUND The cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimers disease (AD). The ketones, acetoacetate and β-hydroxybutyrate, are the brains main alternative energy substrates to glucose. OBJECTIVE To gain insight into brain fuel metabolism in mild AD dementia by determining whether the regional CMR and the rate constant of acetoacetate (CMRa and Ka, respectively) reflect the same metabolic deficit reported for cerebral glucose uptake (CMRg and Kg). METHODS Mild AD dementia (Mild AD; n = 10, age 76 y) patients were compared with gender- and age-matched cognitively normal older adults (Controls; n = 29, age 75 y) using a PET/MRI protocol and analyzed with both ROI- and voxel-based methods. RESULTS ROI-based analysis showed 13% lower global CMRg in the gray matter of mild AD dementia versus Controls (34.2 ± 5.0 versus 38.3 ± 4.7 μmol/100 g/min, respectively; p = 0.015), with CMRg and Kg in the parietal cortex, posterior cingulate, and thalamus being the most affected (p ≤ 0.022). Neither global nor regional CMRa or Ka differed between the two groups (all p ≥ 0.188). Voxel-based analysis showed a similar metabolic pattern to ROI-based analysis with seven clusters of significantly lower CMRg in the mild AD dementia group (uncorrected p ≤ 0.005) but with no difference in CMRa. CONCLUSION Regional brain energy substrate hypometabolism in mild AD dementia may be specific to impaired glucose uptake and/or utilization. This suggests a potential avenue for compensating brain energy deficit in AD dementia with ketones.

Electronic organiser and Alzheimer's disease: Fact or fiction?

Alzheimers disease is a degenerative disease characterised by a progressive loss of cognitive functions and impairment of activities of daily living severe enough to interfere with normal functioning. To help persons with this disease perform a variety of activities, our research team developed AP@LZ, an electronic organiser specifically designed for them. Two participants with Alzheimers disease learned how to use AP@LZ in their daily lives by following a structured learning method. After the learning phase, the participants were able to use AP@LZ efficiently and facilitate their day-to-day activities for several months, despite the steady progression of the disease. These results suggest that persons with Alzheimers disease can learn to use new technologies to compensate for their everyday memory problems, which opens up new rehabilitation possibilities in dementia care.

A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer’s Disease: Preliminary Results from a Neuroimaging Study

BACKGROUND Aerobic training has some benefits for delaying the onset or progression of Alzheimers disease (AD). Little is known about the implication of the brains two main fuels, glucose and ketones (acetoacetate), associated with thesebenefits. OBJECTIVE To determine whether aerobic exercise training modifies brain energy metabolism in mild AD. METHODS In this uncontrolled study, ten patients with mild AD participated in a 3-month, individualized, moderate-intensity aerobic training on a treadmill (Walking). Quantitative measurement of brain uptake of glucose (CMRglu) and acetoacetate (CMRacac) using neuroimaging and cognitive testing were done before and after the Walking program. RESULTS Four men and six women with an average global cognitive score (MMSE) of 26/30 and an average age of 73 y completed the Walking program. Average total distance and treadmill speed were 8 km/week and 4 km/h, respectively. Compared to the Baseline, after Walking, CMRacac was three-fold higher (0.6±0.4 versus 0.2±0.1 μmol/100 g/min; p = 0.01). Plasma acetoacetate concentration and the blood-to-brain acetoacetate influx rate constant were also increased by 2-3-fold (all p≤0.03). CMRglu was unchanged after Walking (28.0±0.1 μmol/100 g/min; p = 0.96). There was a tendency toward improvement in the Stroop-color naming test (-10% completion time, p = 0.06). Performance on the Trail Making A&B tests was also directly related to plasma acetoacetate and CMRacac (all p≤0.01). CONCLUSION In mild AD, aerobic training improved brain energy metabolism by increasing ketone uptake and utilization while maintaining brain glucose uptake, and could potentially be associated with some cognitive improvement.

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance

Objective To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Materials and methods Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. Results The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9–14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. Conclusions The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer’s disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Can people with Alzheimer's disease improve their day-to-day functioning with a tablet computer?

ABSTRACT New technologies, such as tablet computers, present great potential to support the day-to-day living of persons with Alzheimers disease (AD). However, whether people with AD can learn how to use a tablet properly in daily life remains to be demonstrated. A single case study was conducted with a 65-year-old woman with AD. A specific and structured intervention tailored to her needs was conceptualised for the use of a calendar application on a tablet computer according to the following learning stages: Acquisition, Application and Adaptation. In spite of her severe episodic memory deficit, she showed progressive learning of the tablet application during the intervention phase. Furthermore, data compiled over 12 months post-use show that she used the tablet successfully in her day-to-day life. She was even able to transfer her newly acquired ability to other available applications designed to monitor regular purchases, consult various recipes and play games. Tablet computers thereby offer a promising avenue for cognitive rehabilitation for persons with AD. This success was mainly achieved through a one-on-one individual programme tailored to this person. The limits and constraints of utilising tablet computers for persons with AD are discussed.

Impact of AP@LZ in the daily life of three persons with Alzheimer's disease: long-term use and further exploration of its effectiveness.

ABSTRACT AP@LZ is an electronic organiser that was designed to support the day-to-day activities of persons with Alzheimer’s disease. To assess the potential of this technology, three participants (NI, JB, RD) were approached to take part in the study. They benefited from a structured cognitive intervention to learn how to operate AP@LZ; the intervention included the following learning stages: Acquisition, Application and Adaptation. Pre- and post-intervention measures were collected. NI, for whom a longitudinal study was conducted, still continued to use AP@LZ 24 months post-intervention. JB and RD also showed a gradual improvement in their performance throughout the intervention phase (sessions 1 to 19 for JB: performance increased from 50 to 100%; sessions 1 to 25 for RD: from 56 to 89%). The results of the use of AP@LZ in activities of daily living suggest that the application was beneficial for three persons with Alzheimer’s disease whose profiles differed notably (age, cognitive and social profiles). Thus, results indicate that they were all able to learn how to operate AP@LZ’s functions and to use them in their activities of daily living. Cognitive intervention appears to play an important role for the promotion of learning and adoption of such technology.

Orthostatic hypotension associated with executive dysfunction in mild cognitive impairment

INTRODUCTION Midlife hypertension is associated with dementia in longitudinal studies while chronic hypotension in the elderly is associated with dementia onset. Orthostatic hypotension could influence cognitive performance in the elderly. The objective of this study was to assess the relationship between orthostatic hypotension and cognitive functions. METHODS Consecutive participants with complete neuropsychological evaluation from a Memory Clinic were included. Orthostatic hypotension (OH) was defined by a fall≥20/10mmHg systolic/diastolic pressure. Participants were classified into one of 3 groups: 1) subjective cognitive impairment (SCI), 2) mild cognitive impairment (MCI), and 3) dementia. Neuropsychological tests were analyzed for patients with and without OH. RESULTS One hundred and twenty participants were included, of which 16 (13%) were classified as SCI, 42 (35%) as MCI, and 63 (52%) with dementia. Prevalence of OH was 0% for the SCI group, 26% (n=11) for the MCI group, and 38% (n=24) for the dementia group. Age, sex, education, and brief cognitive test scores (MMSE & MoCA) were not different between groups with or without OH. In the MCI group, OH was associated with lower cognitive performance in several executive functions tests: visual working memory (p<0.001), processing speed (p=0.006), Stroop flexibility (p=0.030) and Trail-Making Test part B (p=0.024). There was no difference in episodic memory performance. OH was associated with a diagnosis of hypertension and the use of antihypertensive medication. No differences were observed in vascular brain injury between groups with and without OH. CONCLUSIONS This study found that orthostatic hypotension prevalence is correlated to severity of cognitive deficits in a Memory Clinic. In MCI, OH is associated with lower performance in executive functions. OH could represent an under-recognized correlate of cognitive performance.