Subjective Memory Deficits in People with and without Dementia: Findings from the 10/66 Dementia Research Group Pilot Studies in Low- and Middle-Income Countries

OBJECTIVES To compare subjective memory deficit (SMD) in older adults with and without dementia or depression across multiple centers in low- and middle-income countries (LAMICs). DESIGN Secondary analysis of data from 23 case control studies. SETTING Twenty-three centers in India, Southeast Asia (including China), Latin America and the Caribbean, Nigeria, and Russia. PARTICIPANTS Two thousand six hundred ninety-two community-dwelling people aged 60 and older in one of three groups: people with dementia, people with depression, and controls free of dementia and depression. MEASUREMENTS SMD was derived from the Geriatric Mental State examination. RESULTS Median SMD frequency was lowest in participants without dementia (26.2%) and higher in those with depression (50.0%) and dementia (66.7%). Frequency of SMD varied between centers. Depression and dementia were consistently associated with SMD. Older age and hypochondriasis were associated with SMD only in subjects without dementia. In those with dementia, SMD was associated with better cognitive function, whereas the reverse was the case in controls. CONCLUSION Associations with SMD may differ between subjects with and without dementia living in LAMICs.

Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine.

BACKGROUND: Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC). METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS: Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022905.

Cerebellar transcranial direct current stimulation modulates verbal working memory.

BACKGROUND: Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. OBJECTIVE: We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. METHOD: We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. RESULTS: In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. CONCLUSION: Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions.

Genetic and environmental components of phenotypic variation in immune response and body size of a colonial bird, Delichon urbica (the house martin).

Directional selection for parasite resistance is often intense in highly social host species. Using a partial cross-fostering experiment we studied environmental and genetic variation in immune response and morphology in a highly colonial bird species, the house martin (Delichon urbica). We manipulated intensity of infestation of house martin nests by the haematophagous parasitic house martin bug Oeciacus hirundinis either by spraying nests with a weak pesticide or by inoculating them with 50 bugs. Parasitism significantly affected tarsus length, T cell response, immunoglobulin and leucocyte concentrations. We found evidence of strong environmental effects on nestling body mass, body condition, wing length and tarsus length, and evidence of significant additive genetic variance for wing length and haematocrit. We found significant environmental variance, but no significant additive genetic variance in immune response parameters such as T cell response to the antigenic phytohemagglutinin, immunoglobulins, and relative and absolute numbers of leucocytes. Environmental variances were generally greater than additive genetic variances, and the low heritabilities of phenotypic traits were mainly a consequence of large environmental variances and small additive genetic variances. Hence, highly social bird species such as the house martin, which are subject to intense selection by parasites, have a limited scope for immediate microevolutionary response to selection because of low heritabilities, but also a limited scope for long-term response to selection because evolvability as indicated by small additive genetic coefficients of variation is weak.

Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure.

Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.

A new electrophysiological index for working memory load in humans.

Working memory, the ability to store and simultaneously manipulate information, is affected in several neuropsychiatric disorders which lead to severe cognitive and functional deficits. An electrophysiological marker for this process could help identify early cerebral function abnormalities. In subjects performing working memory-specific n-back tasks, event-related potential analysis revealed a positive-negative waveform (PNwm) component modulated in amplitude by working memory load. It occurs in the expected time range for this process, 140-280 ms after stimulus onset, superimposed on the classical P200 and N200 components. Independent Component Analysis extracted two functional components with latencies and topographical scalp distributions similar to the PNwm. Our results imply that the PNwm represents a new electrophysiological index for working memory load in humans.

Manipulating sleep spindles - expanding views on sleep, memory, and disease.

Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning, and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes.

Immunocompetence and nestling survival in the house martin: the tasty chick hypothesis

In altricial birds post-fledging survival is usually positively related to nestling body mass. A large number of studies have shown that the latest hatched chick is the more likely to die, even if food is abundant. Here we suggest that ectoparasites may be a key factor in the evolution and the maintenance of the establishment of weight hierarchies within broods. We prepose the hypothesis that weight hierarchies within broods may be adaptive if the chick in poor condition is the one with the least efficient immune system within a nest. In this case parasites would preferentially feed on such a "tasty chick", because it would allow high reproductive rates for the parasites, without negatively affecting the survival of the other nestlings. This could prevent entire nest failure of the brood or allow the other chicks to grow more efficiently. This hypothesis was investigated in a colony of house martins Delichon urbica. We predicted that immunocompetence was positively correlated with body condition, and that nestlings dying before hedging should have lower immune responses when challenged with an antigen. T-cell immune response to an experimentally injected antigen was strongly positively related to body condition. Non-surviving chicks had low body condition and a weak immune response. The implications of these results are discussed in the context of the adaptive significance of hatching asynchrony.

Development of allocentric spatial memory abilities in children from 18 months to 5 years of age.

Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a fundamental component of episodic memory, in two versions of a real-world memory task requiring 18 month- to 5-year-old children to search for rewards hidden beneath cups distributed in an open-field arena. Whereas children 25-42-months-old were not capable of discriminating three reward locations among 18 possible locations in absence of local cues marking these locations, children older than 43 months found the reward locations reliably. These results support previous findings suggesting that allocentric spatial memory, if present, is only rudimentary in children under 3.5 years of age. However, when tested with only one reward location among four possible locations, children 25-39-months-old found the reward reliably in absence of local cues, whereas 18-23-month-olds did not. Our findings thus show that the ability to form a basic allocentric representation of the environment is present by 2 years of age, and its emergence coincides temporally with the offset of infantile amnesia. However, the ability of children to distinguish and remember closely related spatial locations improves from 2 to 3.5 years of age, a developmental period marked by persistent deficits in long-term episodic memory known as childhood amnesia. These findings support the hypothesis that the differential maturation of distinct hippocampal circuits contributes to the emergence of specific memory processes during early childhood.

Further characterization of the executive memory impairment following frontal lobe lesions.

In this article we describe a 41-year-old man who, following an operation to repair a ruptured anterior communicating artery aneurysm, manifested the "hallmark" features of a dysexecutive memory impairment. Of particular note was the patient's apparently normal level of recognition memory but impaired recall on tasks matched for difficulty in control subjects. However, further testing revealed that the patient's recognition memory was not normal under all circumstances. Implications of these data for the interpretation and further investigation of the dysexecutive deficit are discussed.