Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort

Abstract

Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov, NCT01926249

Clinical symptoms in mild cognitive impairment with Lewy bodies: Frequency, time of onset, and discriminant ability

“…Our findings are in keeping with previous reports, which have identified high rates of neuropsychiatric, motor, sleep, and autonomic symptoms in MCI-LB or prodromal DLB [6][7][8][9][10]. The control group in our study had higher rates of some symptoms in comparison to other cohorts, such as constipation [6] and drooling/hypersalivation [9]. We recruited MCI participants with possible symptoms related to prodromal DLB; therefore, the rates of the symptoms reported in MCI-AD here may be higher than in the general clinical population.…”

“…significant and is consistent with data published by other groups on the prevalence of autonomic, neuropsychiatric, and other symptoms in MCI-LB[6][7][8][9][10]. These symptoms are also common in DLB.…”

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function

“…Bowel movement abnormalities, such as constipation or diarrhea, have been linked to diseases ranging from enteric infections [18], CKD, and IBD to dementia-related neurodegenerative diseases like Alzheimer's disease (AD) and PD [31,74,75]. Indeed, we see many of the phenotypic markers of these diseases manifested in generally-healthy individuals who report having aberrant BMFs, with constipation in particular associated with a build up of microbially-derived uremic toxins in the blood.…”

Neural basis of impaired narrative discourse comprehension in prodromal and mild dementia with lewy bodies

“…It is of relevance, as the affection of nigrostriatal pathways in either conditions (cognitive or psychiatric onset) can be different ( Hansen et al, 2021 ), possibly in relation with a malfunction of the locus coeruleus ( Hansen, 2021 ) in psychiatric onset patients. Since the locus coeruleus modulates executive functions through the noradrenergic system, and psychiatric symptoms are frequent at the prodromal stage of DLB ( Blanc et al, 2022 ), future studies should explore potential implications of the type of onset of DLB (that is, cognitive, psychiatric or mixed) in this matter. Overall, our results are therefore consistent with the hypothesis that executive dysfunctioning in DLB patients could lead to difficulties in planning and reasoning about the narrative structure.…”