Association between low values of mean arterial pressure and impaired cognitive performance in older patients with mild cognitive impairment: cross-sectional preliminary findings from the STRENGTH Project.

BACKGROUND: Uncontrolled blood pressure (BP) is a risk factor for Mild Cognitive Impairment (MCI) and dementia. AIMS: This study examined the relationship between BP and clinical/cognitive/neuropsychological aspects in MCI individuals. METHODS: MCI patients underwent clinical, functional, cognitive and metacognitive, as well as psychological assessments. Social network, lifestyle characteristics, and medication prescriptions were also evaluated. Each patient underwent BP measurements. RESULTS: Lower values of systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were associated with poorer cognitive performance. Notably, MAP showed greater capability in detecting impairments in attention and visuospatial abilities compared to SBP and DBP. DISCUSSION: These findings support the notion that in older individuals with MCI excessively low BP values, particularly MAP, might represent a risk and suggest that cerebral hypoperfusion may play a key role. CONCLUSIONS: Routine assessment of MAP could aid clinicians in adjusting antihypertensive treatment and closely monitoring cognitive function in MCI patients.

Bacterial DNAemia in Alzheimer's Disease and Mild Cognitive Impairment: Association with Cognitive Decline, Plasma BDNF Levels, and Inflammatory Response.

Microbial dysbiosis (MD) provokes gut barrier alterations and bacterial translocation in the bloodstream. The increased blood bacterial DNA (BB-DNA) may promote peripheral- and neuro-inflammation, contributing to cognitive impairment. MD also influences brain-derived neurotrophic factor (BDNF) production, whose alterations contribute to the etiopathogenesis of Alzheimer's disease (AD). The purpose of this study is to measure BB-DNA in healthy elderly controls (EC), and in patients with mild cognitive impairment (MCI) and AD to explore the effect on plasma BDNF levels (pBDNF), the inflammatory response, and the association with cognitive decline during a two-year follow-up. Baseline BB-DNA and pBDNF were significantly higher in MCI and AD than in EC. BB-DNA was positively correlated with pBDNF in AD, plasma Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) levels in MCI. AD patients with BB-DNA values above the 50th percentile had lower baseline Mini-Mental State Examination (MMSE). After a two-year follow-up, AD patients with the highest BB-DNA tertile had a worse cognitive decline, while higher BB-DNA levels were associated with higher TNF-α and lower IL-10 in MCI. Our study demonstrates that, in early AD, the higher the BB-DNA levels, the higher the pBDNF levels, suggesting a defensive attempt; BB-DNA seems to play a role in the AD severity/progression; in MCI, higher BB-DNA may trigger an increased inflammatory response.

Study of the effects of adapted Tango and multidimensional intervention in pREvention of dementia in agiNG: developing healTHy lifestyle programs (STRENGTH Project)-the experimental protocol of a prospective randomised controlled trial.

BACKGROUND: Dementia represents a key health issue for older adults, with negative consequences on psycho-social and functional status. Treatments that counteract cognitive deficits in mild cognitive impairment (MCI) are needed to prevent or delay it. AIM: To describe the experimental protocol of the STRENGTH Project. This study investigates a multimodal intervention in older adults with MCI to improve cognitive, functional, biochemical and psycho-social aspects. METHODS: The prospective randomised controlled trial will enrol 300 subjects with MCI (age ≥ 60 years). Participants will be randomly assigned to: (a) the experimental group, which will undergo sessions of adapted tango, music therapy, engagement in social activities, cognitive intervention and psycho-education for 6 months or (b) the control group, which will receive psycho-education and advice on healthy lifestyle for 6 months. All outcomes will be analysed before intervention (baseline), immediately after termination (follow-up 1), after 6 months (follow-up 2) and after 2 years (follow-up 3). DISCUSSION: We expect that the findings of this multidisciplinary study will be useful to optimize clinical and psycho-social interventions for improving cognitive and functional status of subjects with MCI. CONCLUSIONS: This project could have a meaningful impact on National Health Systems by providing clues on multidisciplinary management of older adults affected by cognitive decline to prevent dementia.

Effect of a Cognitive Training Program on the Platelet APP Ratio in Patients with Alzheimer's Disease.

In patients with Alzheimer's disease (AD), synaptic plasticity seems to be involved in cognitive improvement induced by cognitive training. The platelet amyloid precursor protein (APP) ratio (APPr), i.e., the ratio between two APP isoforms, may be a useful peripheral biomarker to investigate synaptic plasticity pathways. This study evaluates the changes in neuropsychological/cognitive performance and APPr induced by cognitive training in AD patients participating in the "My Mind Project". Neuropsychological/cognitive variables and APPr were evaluated in the trained group (n = 28) before a two-month experimental protocol, immediately after its termination at follow-up 1 (FU1), after 6 months at follow-up 2 (FU2), and after 24 months at follow-up 3 (FU3). The control group (n = 31) received general psychoeducational training for two months. Some memory and attention parameters were significantly improved in trained vs. control patients at FU1 and FU2 compared to baseline (Δ values). At FU3, APPr and Mini Mental State Examination (MMSE) scores decreased in trained patients. Δ APPr correlated significantly with the Δ scores of (i) MMSE at FU1, (ii) the prose memory test at FU2, and (iii) Instrumental Activities of Daily Living (IADL), the semantic word fluency test, Clinical Dementia Rating (CDR), and the attentive matrices test at FU3. Our data demonstrate that the platelet APPr correlates with key clinical variables, thereby proving that it may be a reliable biomarker of brain function in AD patients.

Aged rats with different performances at environmental enrichment onset display different modulation of habituation and aversive memory.

A wide agreement exists that environmental enrichment (EE) is most beneficial if introduced early in life, but numerous studies reported that also aged animals remain responsive. As age-related memory and cognition impairments are not uniform, an open question is whether EE might exert different effects in animals with different age-related deficits. A 12-week EE protocol was applied to late adult rats pretested for habituation and aversive memory. Animals were classified as low (LP) and high (HP) performers according to percent exploration change in Open Field test (OF) and as impaired (I) and not impaired (NI) according to latency in Step-through Passive Avoidance test (PA). Standard housing (SH) animals pretested by OF and PA, and naïve (non-pretested) EE and SH rats were used as controls. In comparison to pretest, after the housing protocol, EE LP ameliorated while EE HP and both SH HP and LP worsened their habituation pattern. The positive influence of EE on LP was probably due to the more active interaction with and the faster adaptation to surroundings promoted by continuous, multiple stimuli provided during the enriched housing. Regarding HP, EE did not boost the basal behavior, which likely represented the maximum achievable for that age, and the post housing exploration change dropped, as in SH animals, because of the retesting. After EE, a significant percentage of NI animals became I and a significant percentage of I animals became NI. The changes evidenced in the NI group likely depended on EE-related reduction of anxiety and the consequent more efficient coping with fearful situations. This hypothesis was strengthened by the observation that naïve EE animals were almost all I. Pretested EE I rats were not influenced by the rearing condition: their behavior was comparable to SH animals' behavior and determined by retesting. In conclusion, these results demonstrated that, when applied to aging rats, EE produces different effects based on pre-housing cognitive performances. The issue needs further analyses, but the observation that not all animals are able to take advantage of EE to the same extent suggests the opportunity to design individually tailored approaches to optimize their efficacy and minimize possible unwanted consequences.

The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation.

BACKGROUND: Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain. RESULTS: In females, interleukin 1 beta (IL1ß) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1ß and IL10 were significantly higher in treated rats. CONCLUSION: These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains.

The effect of late-life environmental enrichment on stress and anxiety: The role of sex and age-related differences in coping with aversive stimuli.

Anxiety significantly diminishes the quality of life in older adults, and the drugs used for its treatment often come with risky side effects. Non-pharmacological protocols could be valuable, but more research is needed in this area. Environmental enrichment induces positive effects on anxiety-like behavior in young and adult animals; whether the same happens in aged animals is still elusive. The aged brain undergoes changes that contribute to make it "fragile" and consequently even mild, potentially positive stimuli can trigger dyshomeostasis, worsening rather than ameliorating functioning. Here, by combining behavioral analysis and measurement of serum and brain corticosterone levels, we show that late-life environmental enrichment can induce eustress or distress, depending on sex and hypothalamic-pituitary-adrenal axis function. These findings pave the way for optimizing outcomes and minimizing undesired effects in the clinical setting, underscoring the need to overcome the limits of gender medicine and emphasizing the crucial role of individually tailored therapies.

Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients.

COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls without COVID-19 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA variants (40-60% heteroplasmy), and allows the assessment of low-level heteroplasmy (<10% heteroplasmy). Serum concentrations of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic variants in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic variant burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. These findings suggest that SARS-CoV-2 may induce mtDNA mutations that are related to the degree of inflammation.

Early Benefits with Potential Long-Term Risks of a Comprehensive Intervention on Serum Cortisol Levels and Cognitive Performance in Patients with Alzheimer's Disease.

Background: Elevated cortisol levels represent a risk factor for Alzheimer's disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes. Objective: To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD. Methods: CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, n = 45) and control (CG, n = 45) groups. A wide range of sociodemographic, cognitive, psychosocial, and functional conditions were evaluated before, at the conclusion, and 24 months after CI. Data about lifestyle and drug prescription were also recorded. Results: Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG. Conclusions: These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.

Generation and Characterization of the First Murine Model of Alzheimer's Disease with Mutated AßPP Inserted in a BALB/c Background (C.B6/J-APPswe).

BACKGROUND: Numerous mouse models of Alzheimer's disease (AD) are available, but all suffer from certain limitations, thus prompting further attempts. To date, no one model exists with amyloidopathy in a BALB/c strain. OBJECTIVE: To generate and characterize the C.B6/J-APPswe mouse, a model of AD with a mutated human gene for the amyloid-ß protein precursor (AßPP) inserted in a BALB/c background. METHODS: We analyzed five groups at different ages (3, 6, 9, 12, and 16-18 months) of C.B6/J-APPswe and wild-type mice (50% males and 50% females) for the main hallmarks of AD by western blotting, amyloid-ß (Aß) ELISA, immunocytochemistry, electrophysiology, and behavioral tests. RESULTS: The C.B6/J-APPswe mouse displays early AßPP and Aß production, late amyloid plaques formation, high level of Tau phosphorylation, synaptic deficits (reduced density and functional impairment due to a reduced post-synaptic responsiveness), neurodegeneration caused by apoptosis and necroptosis/necrosis, microgliosis, astrocytic abnormalities, and sex-related differences in explorative behavior, anxiety-like behavior, and spatial long-term and working memories. Social housing is feasible despite the intra-cage aggressiveness of male animals. CONCLUSION: C.B6/J-APPswe mice develop most of the distinctive features of AD and is a suitable model for the study of brain atrophy mechanisms and of the differences between males and females in the onset of cognitive/non-cognitive deficits.

Environmental enrichment and the aging brain: is it time for standardization?

Aging entails a progressive decline of cognitive abilities. However, since the brain is endowed with considerable plasticity, adequate stimulation can delay or partially compensate for age-related structural and functional impairment. Environmental enrichment (EE) has been reported to determine a wide range of cerebral changes. Although most findings have been obtained in young and adult animals, research has recently turned to aged individuals. Notably, EE can contribute identifying key lifestyle factors whose change can help extend the "mind-span", i.e., the time an individual lives in a healthy cognitive condition. Here we discuss specific methodological issues that can affect the outcomes of EE interventions applied to aged rodents, summarize the main variables that would need standardization (e.g., timing and duration, enrichment items, control animals and setting), and offer some suggestions on how this goal may be achieved. Reaching a consensus on EE experiment design would significantly reduce differences between and within laboratories, enable constructive discussions among researchers, and improve data interpretation.

Platelet Total PLA2 Activity, Serum Oxidative Level, and Plasma Cu/Zn Ratio: A Vicious Cycle with a Potential Role to Monitor MCI and Alzheimer's Disease Progression.

Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A2 (PLA2) are hydrolases with several functions in the brain, nevertheless their deregulation contributes to neurodegeneration. We evaluated platelet total PLA2 activity (ptotPLA2) in healthy elderly subjects (HE, n = 102), patients suffering from mild cognitive impairment (MCI, n = 90) and AD (n = 91). Platelets are considered "circulating neurons" and ptotPLA2 appears to mirror the cerebral activity. ptotPLA2 of the three cohorts was similar, but in MCI the higher ptotPLA2 the worse the global cognitive status (Mini Mental State Examination score [MMSE]) and in AD the lower ptotPLA2 the more severe the pathology stage (Clinical Dementia Rating [CDR]). Accordingly, MCI with MMSE ≥26 overlapped HE, in MCI with MMSE <26 and in AD with CDR 1 ptotPLA2 increased, in AD with CDR 2 ptotPLA2 decreased. In MCI ptotPLA2 positively correlated with blood oxidation and inflammation, in AD it was the opposite. Finally, Discrimination Index (DI)-calculated multiplying ptotPLA2, oxidative level and Cu/Zn ratio (an inflammation parameter)-differentiated MCI patients who progressed to dementia in the following 24 months and AD patients with the worse pathology development. Summarizing, ptotPLA2 changes during MCI and AD progression, is linked, in opposite way, to oxidative/inflammatory status in MCI and AD and might help, when included in DI, to identify MCI converters to dementia and AD patients with the more severe prognosis. ptotPLA2 may have a diagnostic/prognostic value and be a potential therapeutic target.

In aged rats, differences in spatial learning and memory influence the response to late-life Environmental Enrichment.

It has clearly been demonstrated that cognitive stimulation, physical exercise, and social engagement help counteract age-related cognitive decline. However, several important issues remain to be addressed. Given the wide differences in cognitive impairment found among individuals of the same age, identifying the subjects who will benefit most from late-life interventions is one such issue. Environmental Enrichment (EE) is a particularly valuable approach to do this. In this study, aged (21-month-old) rats were assigned to a better (BL) or a worse (WL) learner group (training phase) and to a non-impaired (NI) or an impaired (I) group (probe phase) by their performance on the Morris Water Maze, using the test performances of adult (12-month-old) rats as the cut-offs. The aged rats were retested after a 12-week EE or standard housing (SH) protocol. After 12 weeks, the performances of SH rats had deteriorated, whereas all rats benefited from EE, albeit in different ways. In particular, the animals assigned to the BL and the NI groups prior to EE still performed as well as the adult rats (performance preservation) whereas, critically, the animals assigned to the WL and the I groups before EE showed such improved performances that they reached the level of the adult rats (performance improvement), despite having aged further. EE seems to induce the preservation in BLs and the improvement in WLs of spatial search strategies and the preservation in NIs and the increase in Is of a focused and protract research of the escape point. Our findings suggest that late-life EE prevents spatial learning and memory decline in still cognitively preserved animals and stimulates residual functional reserve in already cognitively compromised animals. Future research should focus on individually tailored stimulation protocols to improve their effect and afford a better understanding of the underlying processes.

MRI characterization of rat brain aging at structural and functional level: Clues for translational applications.

Magnetic resonance imaging (MRI) paradigms, using non-invasive approaches, can provide relevant findings about brain aging. The attention has been primarily focused on neurodegenerative diseases, while little or nothing has been done to differentiate physiology from pathology. The present study aimed to test diffusion tensor imaging (DTI) and functional MRI (fMRI) metrics to analyze physiological age-related changes in rats at myelin structure and activation level; findings were validated by ex vivo histology. The purpose is to find comparable biomarkers in rodents and humans to allow a reliable translation from pre-clinical to clinical settings. Data evidenced: i) a significantly higher cerebrospinal fluid volume in middle-aged and aged vs. young rats; ii) a progressive alteration of white matter; iii) a significant reduction of evoked activity in aged animals. These results partially mirror the age-related changes in humans and may represent a preliminary step to find reliable tools for a lifelong monitoring with a value for the clinical practice (e.g., to provide support to the early diagnosis of dementia in asymptomatic subjects).

Peripheral inflammatory biomarkers of Alzheimer's disease: the role of platelets.

Alzheimer's disease is an age-dependent neurodegenerative disorder characterized by loss of neurons, synaptic degeneration, senile plaques and neurofibrillary tangles. Besides these hallmarks, increased accumulation of activated microglia, astrocytes and leukocytes adhering to postcapillary venules are observed in the affected brain areas, suggesting the presence of an ongoing inflammatory process. As neuroinflammation triggers the activation of peripheral immune system, many studies have analyzed circulating inflammatory biomarkers, including basal or stimulated levels of cytokines and related molecules in blood of Alzheimer's patients, but with conflicting results. Platelets are an important source of amyloid-ss (Ass) in the circulatory system and play an important pro-inflammatory role. Upon activation, they adhere to leukocytes and endothelial cells by means of adhesive proteins like P-selectin, platelet endothelial cell adhesion molecule-1 (PECAM) and intercellular adhesion molecule-1 and -2 (ICAM-1 and -2) and secrete inflammatory mediators (chemokines, interleukins). In addition, platelets contain important enzymes involved in inflammatory intermediary synthesis like phospholipase A(2) (PLA(2)) and cyclooxygenase-2 (COX-2), and recent reports demonstrated significant changes in platelet levels and activities in Alzheimer's disease. Thus, as platelets represent an important link between Ass deposition and inflammatory reactions especially at endothelial level, they can be considered a valuable cellular model to evaluate potential peripheral inflammatory biomarkers in Alzheimer's disease.

Is Blood Brain-Derived Neurotrophic Factor a Useful Biomarker to Monitor Mild Cognitive Impairment Patients?

Availability of reliable prognostic biomarkers that are also able to monitor preventive/therapeutic interventions in patients with mild cognitive impairment (MCI) is crucial. Cerebral brain-derived neurotrophic factor (BDNF) alterations were evidenced in Alzheimer's disease, but the value of blood BDNF in MCI is unclear, especially because of the incomplete/incorrect management of the numerous confounding factors unrelated to the disease. This study, applying a multidisciplinary methodological approach, aimed at clarifying whether blood BDNF can really mirror the cognitive symptoms of MCI, thus supporting the evaluation of clinical protocols' effectiveness as well as the definition of the conversion rate to dementia. Healthy elderly subjects (HE) and MCI patients were assessed for sociodemographic, neuropsychological, pharmacological, and lifestyle data, and plasma BDNF was measured (baseline); then, in the MCI cohort, the biomarker was tested in a comprehensive cognitive stimulation intervention (CS) as well as in a 2-year follow-up period. Plasma BDNF, cleansed from all the interfering factors, (1) did not discriminate HE and MCI patients; (2) in MCI patients reflected mood, social engagement, and subjective memory complaints but not cognition; (3) changed due to CS, although with no correlations to cognitive performances; and (4) predicted no functional deterioration. Our data indicate that the possible biased use of plasma BDNF in MCI is critically risky.

Platelet as a physiological model to investigate apoptotic mechanisms in Alzheimer beta-amyloid peptide production.

Although neuronal apoptosis in Alzheimer's disease is generally interpreted as the consequence of the toxicity of extracellular beta-amyloid (Abeta) peptide aggregates, some experimental results provide evidence that the Abeta overproduction can be the result of a primary neuronal degeneration. As platelets are considered a good model where to study proteolytic processing of the amyloid precursor protein (APP), we exposed platelets to the proapoptotic agent ionomycin and analyzed Abeta40 and Abeta42 levels in the intracellular and extracellular compartments. The activation of apoptotic pathways in platelets has been verified by mitochondrial membrane depolarization, exposure of phosphatidylserine, protease activation and morphological changes. A significative increase in intraplatelet Abeta40, but not Abeta42, was observed after 10 min treatment with ionomycin. Thus, the activation of apoptotic pathways in platelets determines an altered processing of APP leading to elevated levels of intracellular Abeta40. The specific intracellular production of Abeta40 represents a potential threat to the cells since very high local Abeta40 concentration increases the risk of its aggregation and toxicity. As a result, Abeta40 might be dangerous even before it becomes secreted rendering neurons highly vulnerable.

Brain aging: The zinc connection.

At variance with other organs, where the functional and structural units are repeated, the brain is a composite assembly of groups of cells with different metabolic features and functional units. Deterioration of brain function occurs when the number of neurons or their connections decrease below a critical reserve level and coping with environmental stimulation is seriously hampered. Physiopathological alterations of the synaptic junctional areas are reported to play a central role in the process of brain aging. Current research is documenting an age-related numeric loss of synapses which is paired by a significant enlargement of the persisting contact zones: the final outcome of these balanced changes is a significant reduction of the overall synaptic junctional area per unit volume of neuropil. The progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate is supposed to represent a key determinant in synaptic aging. Cytochemical estimations of the activity of cytochrome oxidase confirm that mitochondrial dysfunctions play an early role in synaptic deterioration. Zinc ions act as physiological neuromodulators at glutamatergic synapses, however, in order to avoid neurotoxic damage, the intracellular free Zn(++) concentration ([Zn(++)](i)) must be tightly controlled by: (i) extrusion (Zn(++) transporters); (ii) buffering (metallothioneins) and (iii) sequestration (mitochondria) systems. In physiological aging, if any of these systems is impaired and/or not adequately coordinated with the other two, the resulting significant rise of ([Zn(++)](i)) may inhibit the cellular energy providing systems and affect mitochondria as primary target.

Long-term visual object recognition memory in aged rats.

Aging is associated with memory impairments, but the neural bases of this process need to be clarified. To this end, behavioral protocols for memory testing may be applied to aged animals to compare memory performances with functional and structural characteristics of specific brain regions. Visual object recognition memory can be investigated in the rat using a behavioral task based on its spontaneous preference for exploring novel rather than familiar objects. We found that a behavioral task able to elicit long-term visual object recognition memory in adult Long-Evans rats failed in aged (25-27 months old) Wistar rats. Since no tasks effective in aged rats are reported in the literature, we changed the experimental conditions to improve consolidation processes to assess whether this form of memory can still be maintained for long term at this age: the learning trials were performed in a smaller box, identical to the home cage, and the inter-trial delays were shortened. We observed a reduction in anxiety in this box (as indicated by the lower number of fecal boli produced during habituation), and we developed a learning protocol able to elicit a visual object recognition memory that was maintained after 24 h in these aged rats. When we applied the same protocol to adult rats, we obtained similar results. This experimental approach can be useful to study functional and structural changes associated with age-related memory impairments, and may help to identify new behavioral strategies and molecular targets that can be addressed to ameliorate memory performances during aging.