Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group. Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences. Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group. Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.

Microglial activation and age-related dopaminergic neurodegeneration in MPTP-treated SAMP8 mice.

Senescence-accelerated mouse prone 8 (SAMP8) has an early onset of senility and a shorter life span, providing with cognitive impairment. Contrasted with C57BL/6 mouse, which is most commonly used in the study of Parkinson's disease (PD), SAMP8 needs shorter period of breeding and might be good candidate for the investigation of cognitive impairment in PD. Studies had shown the increase of sensibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) with aging in C57BL/6 mouse. However, the sensitivity of MPTP neurotoxicity depends on the strains of animal and the exact mechanisms of the progression of PD promoted by aging is lack of consensus. Here, we showed after MPTP injection, the spontaneous activity of both young (3-month-old) and old (6-month-old) SAMP8 decreased dramatically, and the old mice required longer recovery time. Immunohistochemical and immunoblot analysis revealed that old mice displayed significant reductions in the dopaminergic neuron numbers and tyrosine hydroxylase (TH) protein. Microglia protein (CD11b) in the striatum of old mice increased more pronouncedly than that in the young mice from 24 h to 3 days. Inducible nitric oxide synthase (iNOS) in the striatum remarkably increased, however, no discernible difference between the two groups was found. These results suggested that the sensibility to MPTP increased with aging in SAMP8. A greater increase of microglial activation in old mice may be a possible mechanism to explain how advancing age predisposes the dopamine system to parkinsonism. The MPTP-SAMP8 model will start a new consideration for the study of PD.

[Neurotoxicity effect of MPP+ on primary cultured mesencephalon neurons of SAMP8 mouse].

AIM: To investigate the effect of MPP+ on the midbrain neurons of SAMP8 mouse in vitro, which provide the cell model for PD study. METHODS: SAMP8 mouse primary midbrain cell cultures were obtained from mice within 1 day after birth. On the sixth day after culturing, the cultures were treated with 100 micromol/L of MPP+ for 6 hours, 9 hours, 12 hours and 24 hours, then the cells were fixed and followed by immunofluorescence or Western blot analysis for the expressed location and the level of TH respectively. RESULTS: MPP+ led to the morphological changes of primary cultured midbrain neurons of SAMP8 mouse. The neurons had intact morphous with strong immunoreactivity, many and long dendrites in control group. Compared with the control group, the neurons had fewer and thinness dendrites with weak immunoreactivity in MPP+ group. MPP+ significantly decreased midbrain neurons numbers with marked decrease of TH protein levels after its treatment for 9 h. CONCLUSION: MPP+ had neurotoxicity effect on primary cultured midbrain neurons of SAMP8 mouse. Since MPP+ led to marked decrease of neuronal numbers and TH protein levels, it is suggested that MPP+ can cause the DA neuronal degeneration in primary midbrain cell cultures.