Australasian Physical & Engineering Sciences in Medicine, 2019
The inconsistency of volumetric results often seen in MR neuroimaging studies can be partially at... more The inconsistency of volumetric results often seen in MR neuroimaging studies can be partially attributed to small sample sizes and variable data analysis approaches. Increased sample size through multi-scanner studies can tackle the former, but combining data across different scanner platforms and field-strengths may introduce a variability factor capable of masking subtle statistical differences. To investigate the sample size effect on regression analysis between depressive symptoms and grey matter volume (GMV) loss in Alzheimer’s disease (AD), a retrospective multi-scanner investigation was conducted. A cohort of 172 AD patients, with or without comorbid depressive symptoms, was studied. Patients were scanned with different imaging protocols in four different MRI scanners operating at either 1.5 T or 3.0 T. Acquired data were uniformly analyzed using the computational anatomy toolbox (CAT12) of the statistical parametric mapping (SPM12) software. Single- and multi-scanner regression analyses were applied to identify the anatomical pattern of correlation between GM loss and depression severity. A common anatomical pattern of correlation between GMV loss and increased depression severity, mostly involving sensorimotor areas, was identified in all patient subgroups imaged in different scanners. Analysis of the pooled multi-scanner data confirmed the above finding employing a more conservative statistical criterion. In the retrospective multi-scanner setting, a significant correlation was also exhibited for temporal and frontal areas. Increasing the sample size by retrospectively pooling multi-scanner data, irrespective of the acquisition platform and parameters employed, can facilitate the identification of anatomical areas with a strong correlation between GMV changes and depression symptoms in AD patients.
Background: Aberrant motor behaviour or wandering refers to aimless movement without a specific p... more Background: Aberrant motor behaviour or wandering refers to aimless movement without a specific purpose. Wandering is common in patients with dementia and leads to early institutionalization and caregivers’ burden. Non-pharmacological interventions should be also considered as a first-line solution for the wandering because current pharmacological treatment has serious side-effects. Methods: A cross-over randomised controlled trial (RCT) with 60 participants of all stages and different types of dementia was conducted in Greece. The sample was randomly assigned in 6 different groups of 10 participants each. Every intervention lasted for 5 days, and there were 2 days as a wash-out period. There was no drop-out rate. The measurements used were the Mini Mental State Examination (MMSE), Addenbrooke’s Cognitive Examination Revised (ACE-R), Geriatric Depression Scale (GDS), Functional Rating Scale for Symptoms in Dementia (FRSSD), and Neuropsychiatric Inventory (NPI). The interventions tha...
Background: Neuropsychiatric symptoms (NPSs) are common in dementia. Their evaluation is based on... more Background: Neuropsychiatric symptoms (NPSs) are common in dementia. Their evaluation is based on Neuropsychiatric Inventory (NPI). Neuroimaging studies have tried to elucidate the underlying neural circuits either in isolated NPSs or in specific forms of dementia. Objective: : The objective of this study is to evaluate the correlation of NPS in the NPI with Brodmann areas (BAs) perfusion, for revealing BAs involved in the pathogenesis of NPSs in dementia of various etiologies. Method: We studied 201 patients (82 with Alzheimer's disease, 75 with Frontotemporal dementia, 27 with Corticobasal Syndrome, 17 with Parkinson Disease/Lewy Body Dementia). Exploratory factor analysis was carried out to evaluate underlying groups of BAs, and Principal Component analysis was chosen as extraction method using Varimax rotation. Partial correlation coefficients were computed to explore the association of factors obtained from analysis and NPI items controlling for age, educational yeas, and A...
BACKGROUND Eating disorders (ED) in dementia represent a significant impairment affecting patient... more BACKGROUND Eating disorders (ED) in dementia represent a significant impairment affecting patients' and caregivers' lives. In frontotemporal dementia (FTD), ED include overeating, sweet food preference hyperorality, stereotypical eating, and hyperorality, while in Alzheimer's disease (AD), anorexia and appetite loss are the most common ED. OBJECTIVE The aim of our study was to highlight Brodmann areas (BAs) implicated specifically in the appearance of ED in FTD and AD. METHODS We studied 141 patients, 75 with FTD and 66 with AD. We used the NeuroGamTM software on the reconstructed single photon emission computed tomography-SPECT data for the automated comparison of BAs perfusion on the left (L) and right (R) hemisphere with perfusion in corresponding BAs of a normal database. RESULTS The FTD group included 27 men and 48 women, age (mean±SD) 65.8±8.5 years, duration of disease 3.4±3.3 years, Mini-Mental State Examination (MMSE) 17.9±8.6, ED score on Neuropsychiatric Inven...
Agitation/aggressive behaviour is a common behavioural and psychological symptom in people with d... more Agitation/aggressive behaviour is a common behavioural and psychological symptom in people with dementia (PwD), occurring with a frequency of between 13-50.4% according to recent studies, and the rate increases as the severity of cognitive decline increases. The burden on caregivers is considerable. This trial is a randomized controlled crossover trial conducted in Greece. The following measures were used: the Mini-Mental State Examination, Addenbrooke's Cognitive Examination Revised, Geriatric Depression Scale, Functional Rating Scale for Symptoms in Dementia and Neuropsychiatric Inventory. According to the results the most effective nonpharmacological intervention for reducing agitation/aggressive behaviour in PwD was music therapy, followed by aromatherapy and massage, and finally physical exercise.
OBJECTIVE: To present preliminary findings on driving measures of middle aged/older healthy contr... more OBJECTIVE: To present preliminary findings on driving measures of middle aged/older healthy controls and neurology patients in four motorway driving segments (presentation of a traffic sign, start, road works, finish) from two driving simulation environments (low, high traffic). The study examines the contributions of traffic load and driving environment to driving measures in the above groups. It is part of a larger driving simulator experiment funded by NSRF (2007-13) BACKGROUND: Driver performance in different road conditions and especially while driving on the motorway offers valuable information concerning driving safety, but is difficult to investigate during on-road driving. DESIGN/METHODS: Participants: Fifty-four drivers: 24 controls, 20 mild cognitive impairment (MCI) patients, and 10 mild Alzheimer’s disease (AD) patients. Measures: Average speed (in km), lateral position of the vehicle from the right road border (in meters), average headway distance (from the vehicle ahe...
Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are fun... more Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional nuclear medicine techniques which allow for accurate non-invasive in vivo measurements of a wide range of regional tissue functions in man. Brain functional imaging with SPECT and PET is based on the recording of the distribution of administered radionuclides in three dimensions, thus producing maps of brain biochemical and physiological processes. SPECT and PET techniques are able to image brain perfusion and metabolism, as well as various neurotransmission or other cellular processes using specific radioligands which mark in vivo receptors, transporters or enzymes. Brain SPECT and PET imaging or molecular imaging -, has been applied to the study of Alzheimer’s disease (AD) for over two decades. These functional neuroimaging approaches have the capability of identifying subtle pathophysiologic changes in the brain before structural changes are present (Xu et al., 2000). Therefor...
OBJECTIVE: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by a s... more OBJECTIVE: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by a selective loss of language functions. In the nonfluent/agrammatic variant (nfvPPA), speech is slow and hesitant. Utterances are shorter, less complex and contain grammatical errors. Single word production deficits in PPA have been extensively examined. However, connected speech analysis has only recently begun to be systematically studied. The aim of the present study was to investigate connected speech deficits in a Greek-speaking person with nfvPPA.MATERIAL - METHOD: Participant LJ is a 60-year-old right-handed man, with 6 years of formal education. At the time of the study, he had a FTLD-modified CDR score of 9 (MMSE=17/30). A narrative sample was collected using the “cookie theft” picture from BDAE and analyzed following the procedures described by Saffran et al. (1989) for quantitative production analysis (QPA). QPA summary measures, percentages of dysfluent variables and counts of e...
Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and pat... more Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 statu...
International Journal of Psychiatry in Clinical Practice
OBJECTIVES To explore differences of apathy perfusion correlates between Alzheimer's disease ... more OBJECTIVES To explore differences of apathy perfusion correlates between Alzheimer's disease (AD) and Frontotemporal dementia (FTD) using perfusion SPECT. METHODS We studied 75 FTD and 66 AD patients. We evaluated apathy using Neuropsychiatric Inventory (NPI). We compared perfusion of BAs on left (L) and right (R) hemisphere in AD and FTD. RESULTS Apathy in AD was significantly and negatively correlated with dorsolateral prefrontal cortex bilaterally, right anterior prefrontal cortex, inferior frontal cortex bilaterally, especially on the right, orbital part of inferior frontal gyrus bilaterally, left dorsal anterior cingulate cortex, right primary and secondary visual cortex, and with bilateral anterior and dorsolateral prefrontal cortex, inferior frontal cortex and orbital part of inferior frontal gyrus, bilaterally, bilateral anterior -ventral and dorsal- cingulate cortex, left posterior ventral cingulate cortex, right inferior, middle and anterior temporal gyri, entorhinal and parahippocampal cortex in FTD. CONCLUSIONS Significant overlapping of apathy perfusion correlates between AD and FTD is seen in frontal areas and anterior cingulate. Right occipital cortex is also involved in AD, while right temporal cortex and left posterior cingulate are involved in FTD. Nuclear imaging could be a useful biomarker for revealing apathy underlying mechanisms, resulting in directed treatments. KEYPOINTS Underlying neural networks and clinical manifestation of apathy may differ between AD and FTD. Apathy in AD is correlated with hypoperfusion in bilateral frontal areas, more prominent on the right, left anterior cingulate and right occipital cortex. Apathy in FTD is correlated with hypoperfusion in bilateral frontal areas, bilateral anterior cingulate, left posterior cingulate and right temporal cortex. Brain perfusion SPECT with automated BAs analysis and comparison with normal healthy subjects may provide significant information for apathy mechanisms in neurodegenerative disorders, affecting patients' treatment.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of... more Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Beta-amyloid (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein are the pathological hallmarks of the disease, accompanied by other pathological processes such as microglia activation. Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provides valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms. Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation. Intense efforts in radiopharmaceuticals research have led to the development of various probes able to detect Aβ deposits, tau protein accumulation, microglia activation and neuroinflammation. As a result, SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.
Early diagnosis of Alzheimer&... more Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGamTM) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9±8.1 years, mean Mini-Mental State Examination 22.6±2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.
Physical as well as cognitive training interventions improve specific cognitive functions but eff... more Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen's d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.
Australasian Physical & Engineering Sciences in Medicine, 2019
The inconsistency of volumetric results often seen in MR neuroimaging studies can be partially at... more The inconsistency of volumetric results often seen in MR neuroimaging studies can be partially attributed to small sample sizes and variable data analysis approaches. Increased sample size through multi-scanner studies can tackle the former, but combining data across different scanner platforms and field-strengths may introduce a variability factor capable of masking subtle statistical differences. To investigate the sample size effect on regression analysis between depressive symptoms and grey matter volume (GMV) loss in Alzheimer’s disease (AD), a retrospective multi-scanner investigation was conducted. A cohort of 172 AD patients, with or without comorbid depressive symptoms, was studied. Patients were scanned with different imaging protocols in four different MRI scanners operating at either 1.5 T or 3.0 T. Acquired data were uniformly analyzed using the computational anatomy toolbox (CAT12) of the statistical parametric mapping (SPM12) software. Single- and multi-scanner regression analyses were applied to identify the anatomical pattern of correlation between GM loss and depression severity. A common anatomical pattern of correlation between GMV loss and increased depression severity, mostly involving sensorimotor areas, was identified in all patient subgroups imaged in different scanners. Analysis of the pooled multi-scanner data confirmed the above finding employing a more conservative statistical criterion. In the retrospective multi-scanner setting, a significant correlation was also exhibited for temporal and frontal areas. Increasing the sample size by retrospectively pooling multi-scanner data, irrespective of the acquisition platform and parameters employed, can facilitate the identification of anatomical areas with a strong correlation between GMV changes and depression symptoms in AD patients.
Background: Aberrant motor behaviour or wandering refers to aimless movement without a specific p... more Background: Aberrant motor behaviour or wandering refers to aimless movement without a specific purpose. Wandering is common in patients with dementia and leads to early institutionalization and caregivers’ burden. Non-pharmacological interventions should be also considered as a first-line solution for the wandering because current pharmacological treatment has serious side-effects. Methods: A cross-over randomised controlled trial (RCT) with 60 participants of all stages and different types of dementia was conducted in Greece. The sample was randomly assigned in 6 different groups of 10 participants each. Every intervention lasted for 5 days, and there were 2 days as a wash-out period. There was no drop-out rate. The measurements used were the Mini Mental State Examination (MMSE), Addenbrooke’s Cognitive Examination Revised (ACE-R), Geriatric Depression Scale (GDS), Functional Rating Scale for Symptoms in Dementia (FRSSD), and Neuropsychiatric Inventory (NPI). The interventions tha...
Background: Neuropsychiatric symptoms (NPSs) are common in dementia. Their evaluation is based on... more Background: Neuropsychiatric symptoms (NPSs) are common in dementia. Their evaluation is based on Neuropsychiatric Inventory (NPI). Neuroimaging studies have tried to elucidate the underlying neural circuits either in isolated NPSs or in specific forms of dementia. Objective: : The objective of this study is to evaluate the correlation of NPS in the NPI with Brodmann areas (BAs) perfusion, for revealing BAs involved in the pathogenesis of NPSs in dementia of various etiologies. Method: We studied 201 patients (82 with Alzheimer's disease, 75 with Frontotemporal dementia, 27 with Corticobasal Syndrome, 17 with Parkinson Disease/Lewy Body Dementia). Exploratory factor analysis was carried out to evaluate underlying groups of BAs, and Principal Component analysis was chosen as extraction method using Varimax rotation. Partial correlation coefficients were computed to explore the association of factors obtained from analysis and NPI items controlling for age, educational yeas, and A...
BACKGROUND Eating disorders (ED) in dementia represent a significant impairment affecting patient... more BACKGROUND Eating disorders (ED) in dementia represent a significant impairment affecting patients' and caregivers' lives. In frontotemporal dementia (FTD), ED include overeating, sweet food preference hyperorality, stereotypical eating, and hyperorality, while in Alzheimer's disease (AD), anorexia and appetite loss are the most common ED. OBJECTIVE The aim of our study was to highlight Brodmann areas (BAs) implicated specifically in the appearance of ED in FTD and AD. METHODS We studied 141 patients, 75 with FTD and 66 with AD. We used the NeuroGamTM software on the reconstructed single photon emission computed tomography-SPECT data for the automated comparison of BAs perfusion on the left (L) and right (R) hemisphere with perfusion in corresponding BAs of a normal database. RESULTS The FTD group included 27 men and 48 women, age (mean±SD) 65.8±8.5 years, duration of disease 3.4±3.3 years, Mini-Mental State Examination (MMSE) 17.9±8.6, ED score on Neuropsychiatric Inven...
Agitation/aggressive behaviour is a common behavioural and psychological symptom in people with d... more Agitation/aggressive behaviour is a common behavioural and psychological symptom in people with dementia (PwD), occurring with a frequency of between 13-50.4% according to recent studies, and the rate increases as the severity of cognitive decline increases. The burden on caregivers is considerable. This trial is a randomized controlled crossover trial conducted in Greece. The following measures were used: the Mini-Mental State Examination, Addenbrooke's Cognitive Examination Revised, Geriatric Depression Scale, Functional Rating Scale for Symptoms in Dementia and Neuropsychiatric Inventory. According to the results the most effective nonpharmacological intervention for reducing agitation/aggressive behaviour in PwD was music therapy, followed by aromatherapy and massage, and finally physical exercise.
OBJECTIVE: To present preliminary findings on driving measures of middle aged/older healthy contr... more OBJECTIVE: To present preliminary findings on driving measures of middle aged/older healthy controls and neurology patients in four motorway driving segments (presentation of a traffic sign, start, road works, finish) from two driving simulation environments (low, high traffic). The study examines the contributions of traffic load and driving environment to driving measures in the above groups. It is part of a larger driving simulator experiment funded by NSRF (2007-13) BACKGROUND: Driver performance in different road conditions and especially while driving on the motorway offers valuable information concerning driving safety, but is difficult to investigate during on-road driving. DESIGN/METHODS: Participants: Fifty-four drivers: 24 controls, 20 mild cognitive impairment (MCI) patients, and 10 mild Alzheimer’s disease (AD) patients. Measures: Average speed (in km), lateral position of the vehicle from the right road border (in meters), average headway distance (from the vehicle ahe...
Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are fun... more Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional nuclear medicine techniques which allow for accurate non-invasive in vivo measurements of a wide range of regional tissue functions in man. Brain functional imaging with SPECT and PET is based on the recording of the distribution of administered radionuclides in three dimensions, thus producing maps of brain biochemical and physiological processes. SPECT and PET techniques are able to image brain perfusion and metabolism, as well as various neurotransmission or other cellular processes using specific radioligands which mark in vivo receptors, transporters or enzymes. Brain SPECT and PET imaging or molecular imaging -, has been applied to the study of Alzheimer’s disease (AD) for over two decades. These functional neuroimaging approaches have the capability of identifying subtle pathophysiologic changes in the brain before structural changes are present (Xu et al., 2000). Therefor...
OBJECTIVE: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by a s... more OBJECTIVE: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by a selective loss of language functions. In the nonfluent/agrammatic variant (nfvPPA), speech is slow and hesitant. Utterances are shorter, less complex and contain grammatical errors. Single word production deficits in PPA have been extensively examined. However, connected speech analysis has only recently begun to be systematically studied. The aim of the present study was to investigate connected speech deficits in a Greek-speaking person with nfvPPA.MATERIAL - METHOD: Participant LJ is a 60-year-old right-handed man, with 6 years of formal education. At the time of the study, he had a FTLD-modified CDR score of 9 (MMSE=17/30). A narrative sample was collected using the “cookie theft” picture from BDAE and analyzed following the procedures described by Saffran et al. (1989) for quantitative production analysis (QPA). QPA summary measures, percentages of dysfluent variables and counts of e...
Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and pat... more Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 statu...
International Journal of Psychiatry in Clinical Practice
OBJECTIVES To explore differences of apathy perfusion correlates between Alzheimer's disease ... more OBJECTIVES To explore differences of apathy perfusion correlates between Alzheimer's disease (AD) and Frontotemporal dementia (FTD) using perfusion SPECT. METHODS We studied 75 FTD and 66 AD patients. We evaluated apathy using Neuropsychiatric Inventory (NPI). We compared perfusion of BAs on left (L) and right (R) hemisphere in AD and FTD. RESULTS Apathy in AD was significantly and negatively correlated with dorsolateral prefrontal cortex bilaterally, right anterior prefrontal cortex, inferior frontal cortex bilaterally, especially on the right, orbital part of inferior frontal gyrus bilaterally, left dorsal anterior cingulate cortex, right primary and secondary visual cortex, and with bilateral anterior and dorsolateral prefrontal cortex, inferior frontal cortex and orbital part of inferior frontal gyrus, bilaterally, bilateral anterior -ventral and dorsal- cingulate cortex, left posterior ventral cingulate cortex, right inferior, middle and anterior temporal gyri, entorhinal and parahippocampal cortex in FTD. CONCLUSIONS Significant overlapping of apathy perfusion correlates between AD and FTD is seen in frontal areas and anterior cingulate. Right occipital cortex is also involved in AD, while right temporal cortex and left posterior cingulate are involved in FTD. Nuclear imaging could be a useful biomarker for revealing apathy underlying mechanisms, resulting in directed treatments. KEYPOINTS Underlying neural networks and clinical manifestation of apathy may differ between AD and FTD. Apathy in AD is correlated with hypoperfusion in bilateral frontal areas, more prominent on the right, left anterior cingulate and right occipital cortex. Apathy in FTD is correlated with hypoperfusion in bilateral frontal areas, bilateral anterior cingulate, left posterior cingulate and right temporal cortex. Brain perfusion SPECT with automated BAs analysis and comparison with normal healthy subjects may provide significant information for apathy mechanisms in neurodegenerative disorders, affecting patients' treatment.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of... more Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Beta-amyloid (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein are the pathological hallmarks of the disease, accompanied by other pathological processes such as microglia activation. Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provides valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms. Nuclear neuroimaging in AD has made great progress in the past two decades and has extended beyond the traditional role of brain perfusion and glucose metabolism evaluation. Intense efforts in radiopharmaceuticals research have led to the development of various probes able to detect Aβ deposits, tau protein accumulation, microglia activation and neuroinflammation. As a result, SPECT and PET have proposed to serve as biomarkers in recently revised diagnostic clinical criteria for the early diagnosis of AD and the prediction of progression to AD in mild cognitive impairment (MCI) subjects.
Early diagnosis of Alzheimer&... more Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGamTM) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9±8.1 years, mean Mini-Mental State Examination 22.6±2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.
Physical as well as cognitive training interventions improve specific cognitive functions but eff... more Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen's d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.
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