Annalena Venneri

Background: The prodromal phase of Dementia with Lewy bodies (DLB) remains unexplored and poorly defined. This systematic review scrutinised studies on the earliest cognitive DLB deficits, focusing on the most useful neuropsychological tests. Methods: From an initial pool of 2307 articles, 37 articles met inclusion criteria including either a prodromal DLB population or DLB cohorts comprehensive of individuals in prodromal or Mild Cognitive Impairment (MCI) due to Lewy Bodies pathology. These studies included comparisons with healthy controls, MCI due to Alzheimer's Disease (MCI‐AD), or other aetiologies, and patients with established dementia. Results: Mild impairments were found in attention, executive functions, visual perception, and working memory in prodromal DLB patients. Prodromal DLB exhibited worse performance in memory and language than healthy controls, while showing better memory but worse performance in visual perception, attention, and executive tasks than MCI‐AD. Comparisons in some articles with MCI of other aetiologies confirmed the distinctiveness for prodromal DLB of this pattern of impairment. The most used tests to detect prodromal DLB included the Frontal Assessment Battery (FAB), Digit Symbol Substitution Test (DSST), Stroop test, AX continuous performance test (AX‐CPT), digit span backward, Rey‐Osterrieth Complex Figure copy, pareidolia test, and Visual Object and Space Perception battery (VOSP). Conclusions: Prodromal DLB can be detected using test batteries focused on specific cognitive domains and facilitating early diagnosis. It is possible to standardise a targeted test battery centred on specific visuoperceptual and attention domains for early detection of subtle cognitive decline due to Lewy body pathology.

Background: Sexual minorities experience several health disparities. However, risk/protective factors relevant to cognitive health of sexual minority older adults (SMOAs) have not been fully investigated. The aim of this study was to quantify the impact of several psychosocial factors on both subjective and objective cognitive health in SMOAs. Methods: Thirty-nine cognitively unimpaired SMOAs and 30 heterosexual older adults (HOAs) completed an online survey to provide information on psychosocial risks (i.e., depression, anxiety, general stress), subjective cognitive decline (SCD), beliefs about their own memory and dementia worries. SMOAs also completed questionnaires on minority stress and outness. Twenty-seven SMOAs and 24 HOAs underwent a comprehensive neuropsychological assessment. General linear models were used to assess the relationship between psychosocial risks and cognitive health and interactions between sexual orientation and risk factors. Associations between minority stress, outness and cognitive health were assessed in SMOAs only. Results: SMOAs reported worse mental and subjective cognitive health than HOAs, but similar cognitive performance. Worse depression explained more negative beliefs about memory in SMOAs than HOAs. Anxiety and general stress were associated with worse attention/processing speed performance in SMOAs only. Minority stress was associated with higher risk of SCD for language and more negative beliefs about memory, while higher outness levels were associated with better short-term memory. Conclusions: Psychosocial risks affect cognitive health more severely in SMOAs than HOAs. Minority stress affects subjective cognitive health of SMOAs, while outness may provide cognitive resilience. Further investigations are needed to devise prevention strategies aimed at preserving cognitive health in SMOAs.

Background/Objectives: Studies have shown that higher polygenic risk scores (PRSs) for Alzheimer’s disease (AD) are associated with smaller volumes in temporal brain regions typically affected by this disease. These effects have also been found in cognitively unimpaired (CU) older adults. This study aimed to investigate the relationship between PRSs and brain volumes in specific areas associated with early AD. Methods: 342 participants were selected from the Alzheimer’s Disease Neuroimaging Initiative and stratified into three groups: 114 amyloid-positive atrophic (A+N+), 114 amyloid-negative non-atrophic (A−N−), and 114 amyloid-positive non-atrophic (A+N−) people. Linear regressions were performed within each group to investigate associations between PRSs and regional grey matter volumes. Analyses were also repeated after stratifying groups by APOE status and clinical diagnosis. Two sensitivity analyses were run to investigate the impact of APOE and amyloid status and concordance across biomarkers. Multiplicity was controlled for using the Benjamini–Hochberg false discovery rate (FDR) approach. Results: Negative associations were observed between PRSs and volumes of the left amygdala and hippocampus in A+N+, right hippocampus in A+N−, and right posterior cingulate cortex in A−N− participants. Associations were found especially in A−N− participants, both ε4 allele carriers and non-carriers, and mostly confirmed in sensitivity analyses. Associations emerged only in CU and AD participants, but not in people with MCI. None of these findings survived correction for FDR. Conclusions: These findings highlight the potential of PRSs as novel biological indicators for a deeper characterisation of AD-related neural alterations.

Background/Objectives: Aging is one of the greatest risk factors for neurodegenerative diseases such as Alzheimer’s disease (AD). As the disease progresses, neural loss in brain regions, such as the olfactory cortex (OC), i.e., a set of areas including the mediotemporal and orbitofrontal regions, may lead to dysfunction in the sense of smell and affect other brain regions that relate to the olfactory cortex by either afferent or efferent projections. Methods: The objective of this study was to assess sex-related differences in olfactory cortex volume using magnetic resonance imaging in individuals with mild cognitive impairment, probable dementia of the AD type and in healthy older adults, using the Mini-Mental Statement Examination score, years of education, and total intracranial volume as correction factors. Results: Atrophy of the olfactory cortex was observed in patients of both sexes with probable AD dementia. However, at the MCI stage, significant volumetric loss in the OC was detected in females only but not in males. Conclusions: This finding indicates greater pathological effects in this region in females at an earlier disease stage than in males. This study suggests that OC volume loss occurs differently between the sexes in older adults, with volumetric loss being greater in females.

Minor visual phenomena (MVP), such as visual illusions, pareidolias, feeling of presence, and passage hallucinations, are often experienced by patients with Lewy Body Disease (LBD), in addition to complex visual hallucinations (VH), even in the early stages of the disease. This systematic review aimed to provide an up-to-date literature review of the occurrence and prevalence of MVP in LBD and to assess their potential associations both with VH and visuoperceptual and visuospatial deficits. A systematic literature search was carried out in PubMed, Web of Science, APA PsycInfo, Scopus, and Cochrane Library, and a total of 44 articles were included. The included studies showed significant variability in the occurrence of MVP in the LBD population and in the assessment methods used, such as standardized scales (e.g., the noise pareidolia test), semi-structured interviews (e.g., the North-East Visual Hallucinations Interview), and clinical descriptions. Similarly to VH, MVP appears to be highly specific to LBD, helping in differential diagnosis from Alzheimer’s Disease. The overall relationship between MVP, VH, and visuoperceptual/visuospatial deficits remains unclear. Some studies found that MVP (especially pareidolic responses and presence of hallucinations) was positively correlated with VH, yet it is challenging to determine whether MVP can be considered a precursor of future VH development. Negative associations were reported between MVP (especially pareidolias) and visuoperceptual/visuospatial abilities. However, it is not clear whether these deficits serve as independent, exclusive factors in MVP occurrence or if they interact with VH as a contributing component. Gaining insight into the occurrence of these phenomena could prove beneficial for differential diagnosis, prognosis, and prediction of treatment outcomes in patients with LBD.

This national expert-based Delphi-consensus aims at formulating recommendations on the management of dementia care in Italy. This effort seems important and timely given in light of a new scenario arising from a new biological definition of Alzheimer’s disease (AD) and the availability of disease-modifying treatments (DMTs). Methods: the Steering Committee of the Italian Neurological Society for dementia (SINdem) created appropriate statements. Invited SINdem experts were requested to vote on the statements according to a modified three-round Delphi method. Only those statements reaching Grade A (full agreement ≥ 75%) or B (overall agreement ≥ 80% and full disagreement < 5%) were included in the final document. Round answers’ consistency was graded using the Cohen’s k and within-class correlation coefficient. Results: Forty-six experts voted on 20 statements, which focused on the following aspects: i) organization of care services from early diagnosis to the management of advanced clinical stages; ii) access to biomarkers for a biological diagnosis of AD; iii) requirements necessary for the administration of DMTs; iv) main actors and pathways for the management of patients suffering from cognitive disorders. At the end of the process, 4 statements (20%) received a Grade A consensus, while 16 (80%) reached a Grade B consensus. Although the responses reflect heterogeneity among Italian regions, there was a fair degree of consistency for all statements. Conclusion: The high strength of this expert-based Delphi-consensus may offer guidance for improving the patient’s journey of individuals with cognitive decline from a biological diagnosis to DMTs administration and may possibly offer hints to the Health Systems on dementia.

Background: Carrying the Apolipoprotein ( APOE ) ε4 allele lowers age of onset and increases Alzheimer's disease (AD) risk. Neuropathological findings suggest a mixed etiology in many AD patients, and vascular pathology is common. Objective: This study tested the interactive effect of APOE status and multiple vascular comorbidities on white matter (WM) microstructure in aging and early AD. Methods: 195 participants from the VPH-DARE@IT dataset were stratified in low/high vascular burden based on the Framingham Risk Score (BMI version). Tract-based spatial statistics was used for WM analyses. Results: There was a main effect of APOE , with APOE ɛ4 carriers having higher fractional anisotropy (FA) and lower axial diffusivity (AxD), mean diffusivity (MD), and radial diffusivity (RD) than non-carriers. There was a main effect of vascular burden with lower FA and higher AxD, MD, and RD in the high-burden than the low-burden group. A significant interaction between APOE genotype and vascular burden was also found for all diffusion indices. Post-hoc comparisons revealed lower left hemisphere WM integrity when comparing the low risk group (i.e., non-carriers low burden) to intermediate risk groups (i.e., non-carriers high burden or ɛ4 carriers low burden). The contrasts between the two intermediate risk groups showed altered WM integrity bilaterally. Only the non-carriers high burden showed greater alterations in WM integrity when compared with the high risk group (i.e., ɛ4 carriers high burden) mainly in right hemisphere tracts. Conclusions: These findings indicate an interactive effect of a risk gene and vascular comorbidities on WM integrity in aging and early AD.

Background/Objectives: Sexual minority older adults (SMOAs) report greater subjective cognitive decline (SCD) than heterosexual older adults (HOAs). This study aimed to compare the impact of multiple psycho-social risk factors on objective and subjective cognitive decline in HOAs and SMOAs. Methods: Two samples of self-identified HOAs and SMOAs were selected from the English Longitudinal Study of Ageing. Reliable change indices for episodic and semantic memory were created to assess cognitive decline. SCD was self-reported for memory and general cognition. Depressive symptoms, loneliness, marital status and socio-economic status were investigated as risk factors. Results: No between-group differences were found in cognitive decline. Higher depression was associated with greater SCD risk and worse semantic memory decline. The latter effect was stronger in SMOAs. The findings were largely replicated in the sensitivity analysis. Conclusions: Poor mental health may represent the strongest driver of cognitive decline in SMOAs and to a greater extent than in HOAs.

Alzheimer’s disease may be associated with early dopamine dysfunction. However, its effects on neurofunctional alterations in the neurotransmission pathways remain elusive. In this study, positron emission tomography atlases and functional MRI data for 86 older adults with mild cognitive impairment Alzheimer's disease (MCI), 58 with mild Alzheimer's disease-dementia and 76 cognitively unimpaired were combined to investigate connectivity alterations associated with the dopaminergic and cholinergic systems. A cross-sectional design was used to compare neurotransmitter-related functional connectivity across groups and associations between functional connectivity and cognitive performance. The findings show that the Alzheimer's disease dementia group showed a decline in mesocorticolimbic dopamine-related connectivity in the precuneus but heightened connectivity in the thalamus, whereas the Alzheimer's disease-MCI group showed a decline in nigrostriatal connectivity in the left temporal areas. Acetylcholine-related connectivity decline was observed in both Alzheimer's disease-MCI and Alzheimer's disease-dementia primarily in the temporo-parietal areas. Episodic memory scores correlated positively with acetylcholine- and dopamine-related connectivity in the temporo-parietal cortex and negatively with dopamine-related functional connectivity in the fronto-thalamic areas. This study shows that connectivity alterations in acetylcholine and dopamine functional pathways parallel cognitive decline in Alzheimer's disease and might be a clinically relevant marker in early Alzheimer's disease.