How fiber bundle alterations differ in presumed LATE and amnestic Alzheimer's disease.

INTRODUCTION: Typical Alzheimer's disease (AD) and limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies. METHODS: We investigated white matter (WM) fiber bundle alterations, using fixel-based analysis, a state-of-the-art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy. RESULTS: Both amnestic AD and presumed LATE patients exhibited WM alterations in tracts of the temporal and limbic lobes and in callosal fibers connecting superior frontal gyri. In addition, presumed LATE patients showed alterations in callosal fibers connecting the middle frontal gyri and in the cerebello-thalamo-cortical tract. Cortical thickness was reduced in regions connected by the most altered tracts. DISCUSSION: These findings, the first to describe WM fiber bundle alterations in presumed LATE, are consistent with results on cortical atrophy and with the staging system of tau or TDP-43 accumulation. HIGHLIGHTS: Fixel-based analysis revealed white matter (WM) fiber bundle alterations in presumed limbic-predominant age-related TAR DNA-binding protein 43 encephalopathy (LATE) patients identified by isolated episodic/limbic amnesia, the absence of positive Alzheimer's disease (AD) biomarkers, and no other neurological diagnosis after 2 years of follow-up. Presumed LATE and amnestic AD shared similar patterns of WM alterations in fiber bundles of the limbic and temporal lobes, in congruence with their similar limbic cognitive phenotype. Presumed LATE differed from AD by the alteration of the callosal fibers connecting the middle frontal gyri and of the cerebello-thalamo-cortical tract. WM fiber bundle alterations were consistent with results on regional cortical atrophy. The different anatomical patterns of WM degeneration could provide information on the propagation pathways of distinct proteinopathies.

Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer's disease, suspected-LATE and frontotemporal dementia.

BACKGROUND: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls. METHODS: Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy. RESULTS: We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients. CONCLUSIONS: The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.

Hypersomnia and narcolepsy in 42 adult patients with craniopharyngioma.

STUDY OBJECTIVES: To evaluate sleep, sleepiness, and excessive need for sleep in patients with craniopharyngioma (a suprasellar tumor which can affect sleep-wake systems). METHODS: A retrospective study of all adult patients living with craniopharyngioma referred to the sleep clinic, who received a sleep interview, nocturnal polysomnography, multiple sleep latency tests (MSLT), and 18-h bed rest polysomnography. Their sleep measurements were compared with those of age- and sex-matched healthy controls. RESULTS: Of 54 patients screened with craniopharyngioma, 42 were analyzed, 80% of whom complained of excessive daytime sleepiness. Sleep testing revealed that 6 (14.3%) of them had secondary narcolepsy (including one with cataplexy), and 11 (26.2%) had central hypersomnia associated with a medical disorder. Compared with controls, patients were more frequently obese, had a shorter mean sleep latency on MSLT, and slept longer on the first night. There was a nonsignificant trend for patients with (vs. without) narcolepsy and hypersomnia to be younger, to have a higher body mass index, to be more likely to have received radiation therapy, and to have more severe damage to the hypothalamus after surgery. Treatment with stimulants (modafinil, pitolisant, and methylphenidate) was beneficial in 9/10 patients. CONCLUSIONS: Nearly half of the patients with craniopharyngioma and sleep disorders have a central disorder of hypersomnolence (narcolepsy and hypersomnia), which should be investigated and lead to considerations beyond sleep apnea syndrome in these obese patients.

Sweet or Bland Dreams? Taste Loss in Isolated REM-Sleep Behavior Disorder and Parkinson's Disease.

BACKGROUND: Hyposmia and isolated REM sleep behavior disorder are well-established features of prodromal Parkinson's disease (PD). OBJECTIVES: The objective of the present study was to evaluate whether taste loss (reported in PD and possibly suggesting brain stem involvement) is present at the isolated REM sleep behavior disorder stage. METHODS: We assessed taste function using the Taste Strip Test (evaluating 4 concentrations of bitter, sweet, sour, and salty) in 44 participants with isolated REM sleep behavior disorder, 19 with PD, and 29 controls. All participants underwent video-polysomnography, standardized questionnaires, and clinical examination, including olfactory assessment. RESULTS: Participants with isolated REM sleep behavior disorder and PD had lower taste scores than controls. There was no difference between isolated REM sleep behavior disorder and PD cohorts, nor was there any correlation between taste and olfaction, age, disease duration, cognition, or autonomic function. CONCLUSION: This study demonstrates for the first time the presence of taste impairment in isolated REM sleep behavior disorder that is independent of olfactory dysfunction and comparable to participants with PD. © 2021 International Parkinson and Movement Disorder Society.