Welcome to the WCN 2021 Interactive Program
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- Camillo Marra (Italy)
BRAIN METABOLISM, AMYLOID LOAD AND NEUROPSYCHOLOGICAL CORRELATES IN PRECLINICAL DEMENTIA STAGES
- Giacomo Tondo (Italy)
Abstract
Background and Aims:
This multicenter study aimed to investigate the presence of early cognitive, behavioural and brain changes in individuals with subjective cognitive decline (SCD) and pre-Mild Cognitive Impairment (pre-MCI).
Methods:
Data were derived from the RETE-AD project (NET‐2011‐02346784). Ninety-eight subjects (SCD=46; pre-MCI=52) underwent baseline neuropsychological/neurobehavioral evaluation and FDG-PET. Sixty-eight underwent also amyloid-PET. Neuropsychological/Neuropsychiatric measures were analyzed by implementing a Principal Component Analysis (PCA) to identify the emergence of principal clinical profiles.
Results:
FDG-PET revealed brain hypometabolism in 65% of subjects, with a frontal-like pattern as the most frequent (28%). Neuropsychiatric symptoms were highly prevalent in the whole sample (79%). Only 25% of subjects were classified as amyloid-positive. The PCA showed three neuropsychological factors: 1) mnemonic, correlating with hypometabolism in temporal-parietal regions; 2) executive/visuo-motor, correlating with hypometabolism in frontal, occipital cortex and basal ganglia; 3) visuo-spatial/constructional, correlating with metabolism in fronto-parietal cortices. Two neuropsychiatric factors emerged: 1) affective, correlating with hypometabolism in orbito-frontal, cingulate cortex, insula; 2) hyperactive/psychotic, correlating with hypometabolism in widespread frontal, temporal and parietal areas.
Conclusions:
FDG-PET demonstrated altered brain metabolism already in the preclinical dementia phase, amyloid positivity was uncommon. Different neuropsychological/neuropsychiatric profiles emerged in this stage, correlating with neuronal dysfunction in specific brain regions. SCD and pre-MCI represent heterogeneous populations with different possible underlying etiologies, including normal and reverting conditions, brain dysfunctional correlates, as well as neurodegenerative diseases, such as Alzheimer’s disease, frontotemporal degeneration, other tauopathies. All the above indicates the importance of an extensive clinical and instrumental approach for the correct identification of different prognostic patterns.
PLASMA NEUROFILAMENT LIGHT CHAIN AS A USEFUL BIOMARKER IN PRODROMAL PHASES OF ALZHEIMER’S DISEASE
- Deborah Leccese (Italy)
Abstract
Background and Aims:
One of the greatest challenges in Alzheimer’s disease (AD) is the discovery of new non-invasive, sensitive and specific biomarkers, which might be useful in prodromal phases like mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Neurofilament light chain (NfL), a component of neuronal cytoskeleton, is becoming increasingly notable in different neurological diseases including AD, as a valuable marker of neuronal damage. We aimed to assess quantitative differences in plasma NfL levels between SCD, MCI and AD patients investigating the role of NfL in the early stages of AD.
Methods:
We included 16 SCD, 19 MCI and 6 AD patients, who underwent clinical evaluation, neuropsychological assessment, Apolipoprotein E (ApoE) genotyping and plasma NfL analysis with SiMoA assay. Six SCD, 8 MCI, 6 AD patients underwent cerebrospinal fluid (CSF) biomarkers analysis (Aβ1-42, Aβ1-42/1-40, p-tau, t-tau dosage).
Results:
Plasma NfL levels were significantly increased in MCI (22,43 ± 12,74) when compared to SCD patients (12,69 ± 4,84) (p=0,001), but not to AD patients (22,38 ± 3,09). NfL levels were significantly correlated with p-tau (p=0,029) in SCD, with t-tau (p=0,047) and p-tau (p=0,028) in MCI, while no association with CSF biomarkers was found in AD patients.
Conclusions:
Plasma NfL levels increased in MCI compared to SCD, showing a correlation with tau pathology in SCD and MCI patients. Considering the correlation with p-tau, suggestive of AD, plasma NfL levels might be a useful biomarker of neurodegeneration in prodromal phases of AD.
GENDER DIFFERENCES IN COGNITIVE RESERVE: IMPLICATION FOR SUBJECTIVE COGNITIVE DECLINE IN WOMEN.
- Giulia Giacomucci (Italy)
Abstract
Background and Aims:
Subjective Cognitive Decline (SCD) is as a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase risk of Alzheimer’s Disease. The aim of our study was to evaluate factors influencing age at onset and severity of SCD.
Methods:
We included 381 SCD patients, who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), evaluation of cognitive complaints by the Memory Assessment Clinics-Questionnaire (MAC-Q), and Apolipoprotein E (APOE) genotyping.
Results:
Proportion between women and men was significantly different (68.7%, 95% C.I. 63.9–73.4 vs 31.4%, 95% C.I. 26.6–36.0). Women were younger than men at onset of SCD and at the baseline visit (p=0.021), had lower years of education (p=0.007), lower TIB scores (p<0.001), and higher MAC-Q scores (p=0.012). TIB was directly associated with age at onset of SCD both in women and men, while years of education was inversely associated with age at onset only in women (Fig.1). Multivariate analysis showed that sex influences TIB independently from years of education (Fig.2). TIB was directly associated with MAC-Q in men.
Conclusions:
Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve (CR) in women.
NEUROPSYCHOLOGICAL PREDICTORS OF MCI CONVERSION TO DEMENTIA AT DIFFERENT TIMEPOINTS.
- Davide Quaranta (Italy)
Abstract
Background and Aims:
Episodic memory tests represent are considered as the most valuable tool to identify subjects with MCI who will convert to dementia, but different neuropsychological markers may predict the conversion to dementia at different timepoints from the baseline assessment. The study was aimed at exploring the predicitve value of different neuropsychological markers.
Methods:
We recruited 192 individuals with amnesic MCI due to Alzheimer’s Disease (AD), followed-up for 5 years. 121 individuals converted to dementia. They were subdivided into early converters (EC; conversion in two years; N=63); intermediate converters (IC; between 2 and 4 years; N=37); late converters (LC; over 4 years; N=21). The neuropsychological evaluation included: MMSE; Rey Auditory Verbal Learning Test; digit span; Raven’s Matrices; Stroop’s test; Multiple Features Targets Cancellation; phonological (PVF) and semantic verbal fluency (SVF). The discrepancy between semantic and phonological verbal fluency (SPD) was computed.
Results:
On univariate analyses, EC was predicted by MMSE (p<0.001); RAVLT immediate (p=0.005) and delayed (p=0.007) recall; digit span backward (p=0.033). IC was predicted by MMSE (p<0.001); and SVF (p=0.012). LC was predicted by PVF (p=0.008) and SPD (p=0.05). On the multivariate model, EC was predicted by MMSE (p<0.001); RAVLT immediate recall (p=0.046); and SPD (p=0.026); IC was predicted by MMSE (p<0.001); LC was predicted by SPD (p=0.011).
Conclusions:
Episodic memory tests confirm to be reliable in detecting patients progressing to dementia, but only in the first two years. The conversion over 4 years was predicted only by the SPD, suggesting that semantic memory may be affected in a very early phase of AD.
INTERACTION BETWEEN COGNITIVE RESERVE AND BRAIN COMPLEXITY TO MITIGATE THE IMPACT OF ATROPHY IN EARLY ALZHEIMER’S DISEASE.
- Marco Bozzali (Italy)
Abstract
Background and Aims:
We aimed here at investigating the effect of cognitive reserve (CR) in modulating cortical brain architecture across Alzheimer’s disease (AD) progression.
Methods:
278 individuals (110 AD, 104 mild-cognitive-impairment (MCI) due to AD patients, 64 healthy controls) underwent neuropsychological testing and MR scanning at 3T. T1-weighted volumes were processed using CAT-12 to assess cortical thickness (CTh) and fractal dimension (FD) (a measure of cortical complexity). Education was used as proxy measure of CR to divide each studied group in individuals with high (HCR) and low CR (LCR). Differences in cortical complexity explained by CR were assessed within groups using a t-test model in SPM12. Correlations were also investigated between cognitive scores and cortical complexity.
Results:
No significant demographic differences were observed within groups stratified by CR. HCR- compared to LCR-MCI patients showed smaller CTh in the right temporal and left prefrontal lobes, and increased FD in the right temporal and left temporo-parietal lobes. HCR-AD against LCR-AD patients showed smaller CTh in several cortical regions alongside reduced FD in left temporal cortices. HCR- compared to LCR-controls showed increased CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortex. A positive association was found between brain complexity and performance on memory and executive tests in HCR-MCI patients.
Conclusions:
CR accounts for cortical complexity in patients (but not in healthy subject) at the stage of MCI showing both atrophic changes (neurodegeneration) and richer patterns of brain folding (reserve mechanisms) in temporo-parietal areas. This further confirms a strict time-window for CR effects and possible interventions.
ACCURACY OF FDG-PET AT THE INDIVIDUAL LEVEL IN MCI-LB VERSUS MCI-AD: A STEPWISE APPROACH FROM VISUAL TO SEMI-QUANTITATIVE ANALYSIS
- Federico Massa (Italy)
Abstract
Background and Aims:
FDG-PET is an established supportive biomarker in dementia with Lewy bodies (DLB), but its diagnostic accuracy is unknown in prodromal stages (MCI-LB) when the typical metabolic pattern may be difficultly recognized at the individual level. Semiquantitative analysis of scans can enhance accuracy especially in less skilled readers, but its added role with respect to visual assessment at this DLB stage is still unknown.
Methods:
We assessed the diagnostic accuracy of visual assessment of FDG-PET by six expert readers, blind to diagnosis, in discriminating two matched groups of patients (40 with prodromal AD, MCI-AD, and 39 with MCI-LB), both confirmed by in vivo biomarkers of either amyloidosis or nigrostriatal impairment, respectively. Readers were then provided in a stepwise fashion with i) T-maps obtained by the univariate single-subject voxel-based analysis (VBA) with respect to a control group of 40 age- and sex-matched healthy subjects, and ii) individual odds-ratio (OR) plots obtained by the volumetric regions of interest (VROI) semiquantitative analysis of the two main hypometabolic clusters deriving from the comparison of MCI-AD and MCI-LB patients in the two directions, respectively.
Results:
Mean diagnostic accuracy of visual assessment was 76.8±5.0% and did not significantly benefit from adding the univariate VBA T-map reading (77.4±8.3%) whereas VROI-derived OR plot reading significantly increased both accuracy (89.7±2.3) and inter-rater reliability (ICC 0.97[0.96-0.98]), regardless of the readers’ expertise.
Conclusions:
Conventional visual reading of FDG-PET is moderately accurate, is not significantly improved by univariate single-subject VBA but by a VROI analysis built on macro-regions, independently of reader skills.
MUSCARINIC RECEPTOR EXPRESSION IN THE PERIPHERAL BLOOD CELLS DIFFERENTIATES DLB FROM AD
- Claudia Carrarini (Italy)
Abstract
Background and Aims:
Central Nervous System (CNS) disruption of cholinergic (Ach) signaling, which plays a major role in cognitive processes, is well documented in Dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD) (1,2). The expression of muscarinic Ach receptors type 1 and 4 (CHRM1 and CHRM14) have been reported to be altered in the brain of DLB patients (3). The aim of the present study was to assess the peripheral expression of CHRM1 and CHRM4 in DLB as compared to AD subjects.
Methods:
Peripheral mononuclear blood cells (PMBC) from peripheral venous blood samples were collected from 21 DLB and 13 AD matched patients. Real time-polymerase chain reaction (RT-PCR) was performed to estimate the gene expression of CHRM1 and CHRM4.
Results:
Peripheral CHRM1 and CHRM4 expression was significantly lower in DLB, compared to AD patients. Receiver operating characteristics curves, with logistic regression analysis, showed that, combining peripheral CHRM1 and CHRM4 levels, DLB and AD subjects were classified with an accuracy of 0.76.
Conclusions:
A lower expression of CHRM1 and CHRM4 in DLB subjects, compared to AD at a peripheral level, could be associated with greater cholinergic derangement in DLB and could also represent a suitable biomarker for differential diagnosis and therapeutic response to cholinesterase inhibitors.
DEMENTIA AND COGNITIVE DISORDERS AMONG INTERNATIONAL MIGRANTS LIVING IN ITALY: FINDINGS FROM THE IMMIDEM SURVEY
- Marco Canevelli (Italy)
Abstract
Background and Aims:
The occurrence of cognitive disorders among international migrants is increasing in most western countries and can assume special clinical and public health relevance. The aims of the present study were i) to estimate the number of migrants attending Italian dementia services, and ii) to identify possible barriers and resources surrounding this issue.
Methods:
A nationwide survey of all Italian memory clinics (CCDDs, centers for cognitive disorders and dementia) was conducted between December 2020 and April 2021. The representatives of CCDDs were asked to fill a questionnaire to collect information on i) the number of migrants (i.e., people born abroad) attending these services in 2019, ii) the main complexities encountered in the clinical assessment of cognitive disturbances in migrants, and iii) possible facilitators in the provision of care.
Results:
Overall, 343 out of the 570 contacted CCDDs returned the completed survey questionnaire (response rate: 60.2%). A total of 4,530 migrants attended Italian dementia services in 2019, accounting for 1.7% of overall referrals, with wide variations by region, setting, and administrative features. 37.9% of centers reported that the number of migrants undergoing clinical evaluation had increased over the past 5 years. A minority of CCDDs had information material on dementia in languages other than Italian, translated cognitive tests, or cross-cultural assessment tools. Conversely, most services reported the possibility of contacting social care providers, cultural mediators, and/or interpreters.
Conclusions:
This is the first attempt to provide a nationwide characterization of the issue of dementia in migrants living in Italy.