Differences of apathy perfusion correlates between Alzheimer's disease and frontotemporal dementia. A 99mTc-HMPAO SPECT study with automated Brodmann areas analysis.

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.KEYPOINTSUnderlying 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.

The impact of COVID-19 pandemic on people with mild cognitive impairment/dementia and on their caregivers.

BACKGROUND: The novel coronavirus disease (COVID-19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across the affected populations. AIMS: The aim of the current study was to analyze the impact of COVID-19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well. MATERIALS AND METHODS: Two hundred and four caregivers took part in the study, completing a self-reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece. RESULTS: Results indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this period, where the available support sources were limited. DISCUSSION: The pandemic threatens to disrupt the basic routines that promote mental and physical health of both people with MCI/dementia and t heir caregivers. CONCLUSION: Further measures to protect and provide support to people who suffer and their families are needed.

Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders.

OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. RESULTS: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.

Anosognosia in Dementia: Evaluation of Perfusion Correlates Using 99mTc-HMPAO SPECT and Automated Brodmann Areas Analysis.

(1) Background: Considerable inconsistency exists regarding the neural substrates of anosognosia in dementia in previous neuroimaging studies. The purpose of this study was the evaluation of anosognosia perfusion correlates across various types of dementia using automated Brodmann areas (BAs) analysis and comparison with a database of normal subjects. (2) Methods: We studied 72 patients: 32 with Alzheimer's disease, 26 with frontotemporal dementia-FTD (12 behavioral FTD, 9 semantic FTD, 5 Progressive Non-Fluent Aphasia), 11 with corticobasal syndrome, and 3 with progressive supranuclear palsy. Addenbrook's Cognitive Examination-Revised (ACE-R) mean(±SD) was 55.6(±22.8). For anosognosia measurement, the Anosognosia Questionnaire-Dementia was used. Total anosognosia score mean(±SD) was 22.1(±17.9), cognitive anosognosia score mean(±SD) was 18.1(±15.1) and behavioral-mood anosognosia score mean(±SD) was 3.3(±4.7). (3) Results: Higher anosognosia total score was associated with hypoperfusion in the inferior temporal, anterior cingulate, and inferior frontal cortices of the right hemisphere (BAs 20R, 24R, 32R, 45R). Higher anosognosia cognitive score was correlated with hypoperfusion in the left middle and anterior temporal cortices, and right dorsal anterior cingulate cortex (BAs 21L, 22L, 32R). No association was found with behavioral-mood anosognosia. (4) Conclusions: Automated analysis of brain perfusion Single Photon Emission Computed Tomography could be useful for the investigation of anosognosia neural correlates in dementia.

Correlation of Neuropsychiatric Symptoms in Dementia with Brain Perfusion: A 99mTc-SPECT-HMPAO Study with Brodmann Areas Analysis.

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. METHODS: 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 ACE-R. RESULTS: We found 6 BAs Factors(F); F1 (BAs 8,9,10,11,24,32,44,45,46,47, bilaterally), F2 (BAs 4,5,6,7,23,31, bilaterally), F3 (BAs 19,21,22,37,39,40, bilaterally), F4 (BAs 20,28,36,38, bilaterally), F5 (BAs 25, bilaterally) and F6 (BAs 17,18, bilaterally). Significant and negative correlation was found between NPI1 (delusions) and F3,F6, NPI2 (hallucinations) and F6, NPI7 (apathy) and F1,F4,F5, NPI3 (agitation) - NPI10 (aberrant motor behavior) - NPI12 (eating disorders) and F1. We did not find any significant correlation for NPI4,5,6,8,9,11 (depression, anxiety, euphoria, disinhibition, irritability, sleep disorders, respectively). CONCLUSION: Several NPSs share the same BAs among different types of dementia, while the manifestation of the rest may be attributed to different neural networks. These findings may have an impact on patients' treatment.

Eating Disorders in Frontotemporal Dementia and Alzheimer's Disease: Evaluation of Brain Perfusion Correlates Using 99mTc-HMPAO SPECT with Brodmann Areas Analysis.

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, 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 Inventory (NPI) 4.7±8.5. ED in FTD were correlated with hypoperfusion in right anterior and dorsolateral prefrontal cortices (BAs 10R, 46R), left orbitofrontal cortex (BA 12L), orbital part of the right inferior frontal gyrus (BA 47R), and left parahippocampal gyrus (BA 36L). The AD group included 21 men and 45 women, age (mean±SD) 70.2±8.0 years, duration of disease 3.3±2.4 years, MMSE 20.2±6, ED-NPI score 2.7±3.9. ED in AD were correlated with hypoperfusion in left inferior temporal cortex (BA 20L). CONCLUSION: SPECT imaging with automated mapping of brain cortex could contribute to the understanding of the neural networks involved in the manifestation of ED in dementia.

Conjugate eye deviation as predictor of acute cortical and subcortical ischemic brain lesions.

OBJECTIVES: Non-enhanced computed tomography (NECT) of the brain is used to exclude intracranial hemorrhage in patients who are considered for treatment with tissue plasminogen activator due to stroke symptoms. However, early infarct signs on NECT have low sensitivity for ischemic stroke. It was hypothesized that horizontal conjugate eye deviation (average ocular gaze deviation-OGD >14°) on NECT predicts ischemic brain injury on a second detailed examination. PATIENTS AND METHODS: Patients who underwent brain NECT within three hours after the onset of stroke symptoms and subsequently had brain CT scan with intravenous contrast or MRI were potential participants. OGD was measured from the cross-sectional image including both globes at their maximum diameter. RESULTS: 73 subjects were studied (mean age 64.2±20.8 years) with a median interval (interquartile range) of 56 h (22-109.3 h) between NECT and the second examination. On NECT, 24 of 73 (32.9%) subjects had OGD >14°. Of 32 individuals with acute ischemic injury on the second examination, 19 (59.4%) had OGD >14° on NECT. OGD >14° was associated with increased risk of ischemic injury: OR=10.5 (95% confidence interval 3.33-33.9); P=0.002. OGD >14° had significantly higher sensitivity and negative predictive value than early infarct signs on NECT (59.4% vs. 21.9% and 73.5% vs. 59.7%, respectively; P<0.05), and similar specificity and positive predictive value (87.8% vs. 90.2% and 79.2% vs. 63.6%; P>0.05). CONCLUSION: In the presence of stroke symptoms, average OGD >14° on the initial brain NECT is early predictor of ischemic brain injury.

Diffusion tensor imaging (DTI) in the detection of white matter lesions in patients with mild cognitive impairment (MCI).

Mild cognitive impairment (MCI) is recognized as a precursor to dementia. The amnestic MCI progresses usually to Alzheimer disease. Amnestic MCI multiple domain (md-MCI) seems to progress more rapidly than amnestic MCI single domain (a-MCI). In an attempt to identify patients at risk, we examined white matter changes in MCI subtypes using diffusion tensor imaging (DTI). We also tried to correlate DTI findings to neuropsychological tests. Forty-four amnestic single domain (a-MCI) patients, 19 amnestic multi domain (md-MCI), and 25 cognitively normal (NC) controls were included in the present study. All participants were assessed clinically using a battery of cognitive tests. DTI was performed to measure fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Areas studied were corpus callosum, posterior cingulum (PC), anterior cingulum (AC), and superior longitudinal fasciculus (SLF). ADC and FA of the above areas were related to the scores of certain neuropsychological tests that evaluate visual and verbal memory. No difference in DTI measurements was found between the two MCI subtypes. ADC in MCI cases was increased in comparison with NC in the genu, PC, right SLF, and left AC. FA was spared. Verbal memory was related to ADC of the genu, PC, right AC and right SLF, and to FA of the left SLF. Visual memory was related to ADC of the genu, PC, right AC, and SLF. The strongest correlation found was between the visual memory and the ADC of the right PC (Spearman ρ = 0.45, p < 0.001). DTI revealed that ADC was increased in certain brain areas in MCI patients. No difference in DTI measurements was found between the two MCI subtypes. DTI indices correlate with cognitive performance.