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

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.

Insular cognitive impairment at the early stage of dementia with Lewy bodies: a preliminary study.

BACKGROUND: The anterior part of the insula appears atrophied in the early stage of dementia with Lewy bodies (DLB) whereas it is not the case in early Alzheimer's disease (AD). OBJECTIVE: The objective of this study was to develop neuropsychological markers supposed to reflect insular dysfunction, which would facilitate early diagnosis of DLB, namely in comparison to AD. METHODS: Twelve patients with DLB, 12 patients with AD, all at the stage of Mild cognitive impairment (MCI) or mild dementia, as well as 10 Controls subjects (CS) participated in the study. Cognitive functions supposedly related to the insula were evaluated with a battery of tests: a facial expression recognition test, a test assessing the feeling of disgust with images, a test evaluating idioms' comprehension, an empathy questionnaire and a questionnaire screening for disgusting behaviors. RESULTS: Compared to AD patients and CS, DLB patients experienced less disgust when they were shown disgusting images, whereas their ability to recognize emotional expression of disgust appeared to be preserved. Furthermore, DLB patients seemed less empathetic than AD patients. Finally, compared to CS, DLB patients were less effective to provide an intuitive decision about idioms' signification since they needed significantly more time to answer. CONCLUSION: This preliminary study suggests the existence of a potential « insular cognitive impairment ¼ profile in DLB at the early stage. These results provide interesting leads to develop tools facilitating the differential diagnosis of DLB and AD.

Cognitive profile in prodromal dementia with Lewy bodies.

BACKGROUND: Cortical and subcortical cognitive impairments have been found in dementia with Lewy bodies (DLB). Roughly, they comprise visuoconstructive and executive dysfunction, whereas memory would remain relatively spared. However, the cognitive profile of patients with prodromal DLB remains poorly illustrated to date. METHODS: We included 37 patients with prodromal DLB (age 67.2 ± 8.6 years, 18 men, Mini Mental State Examination [MMSE] score 27.4 ± 2) and 29 healthy control subjects (HCs; age 68.8 ± 7.9 years, 15 men, MMSE score 29.0 ± 0.9). They were presented with an extensive neuropsychological test battery to assess memory; speed of processing; executive function; visuoperceptual, visuospatial and visuoconstructive abilities; language; and social cognition. RESULTS: Compared with HCs, patients had lower scores on a visual recognition memory test (Delayed Matching to Sample-48 items; p ≤ 0.021) and lower free recall (all p ≤ 0.035), but not total recall, performance on a verbal episodic memory test (Free and Cued Selective Reminding Test). Short-term memory (p = 0.042) and working memory (p = 0.002) scores were also lower in patients. Assessment of executive function showed no slowing but overall lower performance in patients than in HCs (all p ≤ 0.049), whereas assessment of instrumental function yielded mixed results. Indeed, patients had lower scores on language tests (p ≤ 0.022), apraxia for pantomime of tool use (p = 0.002) and imitation of meaningless gesture (p = 0.005), as well as weakened visuospatial abilities (p = 0.047). Visuoconstruction was also impaired in patients. However, visuoperceptual abilities did not differ between groups. Finally, theory of mind abilities were lower in patients than in HCs (p < 0.05), but their emotion recognition abilities were similar. CONCLUSIONS: This study presents the cognitive profile in patients with prodromal DLB. In line with the literature on DLB with dementia, our results show lower performance on tests of executive function and visuoconstruction. However, we found, from a prodromal stage of DLB, memory (free recall and visual recognition) and social cognition deficits, as well as weakened visuospatial and praxic abilities.

Comparative study of false memory in dementia with Lewy bodies and Alzheimer's disease.

The production of false memories (FMs) is a normal phenomenon, which can be affected in neurodegenerative diseases such as Alzheimer's disease (AD). Only few studies investigated FMs in patients with dementia with Lewy bodies (DLB). The aim of our preliminary study was to assess FMs in patients with DLB and to identify the underlying cognitive deficits influencing the production of FMs in DLB and AD. Ten AD patients and nine DLB patients performed a memory task (free recall and recognition) coupling two paradigms, namely the DRM (Deese-Roediger-McDermott) paradigm, promoting the production of FMs and the "Remember/Know" (R/K) paradigm, allowing to investigate the phenomenological experience during the recollection of a memory. A standard cognitive evaluation of memory, executive and instrumental functions completed the assessment. No FM was found in the DLB group during free recall, while the number of FMs was substantially identical in both groups during recognition. However, FMs differed from the phenomenological experience, with more K responses in DLB patients and more R responses in AD patients. None of the tests of the standard neuropsychological evaluation did correlate with measures of interest of FMs. In AD patients, the R responses associated with FMs reflect an alteration of the source memory. In DLB patients, the critical item lead to a sense of familiarity, without recollection of the circumstances in which the item was encoded, hence the K responses. This indicates a preservation of their source memory. Contrary to expectations, the type of FMs in both groups was not correlated to their cognitive profile. Hence, cognitive processes underlying the FMs appear to be different in AD and the LBD, but FMs seem independent of memory and executive abilities in these diseases.