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PubMed2001

Anti-stress activity of Indian Hypericum perforatum L.

Indian Hypericum perforatum (IHp) was investigated on a 14-day mild, unpredictable and inescapable foot shock stress (FSS) induced perturbations in behaviour (depression), suppressed male sexual behaviour and cognitive dysfunction in albino rats. Gastric ulceration, and adrenal gland and spleen weights, were also used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. FSS induced marked gastric ulceration, significant increase in adrenal gland weight with concomitant decrease in spleen weight. Chronic stress also suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests). All these FSS induced perturbations were attenuated dose dependently by IHp (100 and 200 mg/kg, po) and PG (100 mg/kg, po). The results indicate that IHp has significant anti-stress activity, qualitatively comparable to PG, against a variety of behavioural and physiological perturbations induced by chronic stress, which has been proposed to be a better indicator of clinical stress than acute stress, and may indicate adaptogenic activity.

Animals↗

PubMed2005

Neurobehavioral effects of interferon therapy.

Interferon (IFN) therapy is associated with neuropsychiatric side effects including cognitive dysfunction and mood syndromes of varying severity. These problems are the most common causes of treatment discontinuation. Dose and duration of treatment influence risk of IFN-induced side effects. Rates of IFN-induced depression vary, but approach 50% in recent studies. Presence and severity of depressive symptoms at or before treatment predicts development of mood disorders during IFN therapy. Several possible endocrine and neurotransmitter perturbations may be responsible for IFN neurotoxicity, with recent research suggesting different symptoms clusters are related to different underlying mechanisms. The interpretation of these clusters has been influenced by subjective versus objective evaluation of cognitive function. Effective management of IFN-induced neuropsychiatric side effects should involve pretreatment screening and interval assessment during therapy. Antipsychotic and psychostimulant drugs may be used against cognitive dysfunction. Antidepressants have been shown to be effective against IFN-induced depression and can be very valuable in support of adequate or completed therapy.

Antidepressive Agents↗

PubMed1985

A new method of measuring brain atrophy: the effect of aging in its application for diagnosing dementia.

A new method of measuring cerebral atrophy using a ratio of brain parenchyma to ventricular and subarachnoid space is described. It uses digitized brain CT. This ratio was measured prospectively on 117 consecutive elderly patients referred for evaluation of cognitive dysfunction. Diagnosis was determined by preestablished criteria and confirmed by follow-up. Despite the improved accuracy and reproducibility of this method, its ability to differentiate persons with senile dementia of the Alzheimer's type (SDAT) from those suffering from pseudodementia was confounded by age, and was hence of limited utility. We conclude that even with sophisticated measures of cerebral atrophy, CT is unable to discriminate among common causes of cognitive dysfunction in the elderly.

Aged↗

PubMed1988

[Temporal lobe epilepsy. Developmental psychiatric study of a surgically treated series].

The authors have studied psychiatrically, pre and post-operatively, a series of 31 cases operated upon for temporal lobe epilepsy. They have concluded that medically uncontrollable limbic epilepsy is associated in its physiopathological substrate to: pathological irritability, affective tenacity, impulsiveness, epileptic cognitive dysfunction and abstraction deficiencies of intellectual process. The high incidence of these events in the patients studied demonstrate the existence of a causal relationship between these abnormalities and the limbic epilepsy. Unilateral temporal lobectomies have been demonstrated to be very efficient for the control of epileptic seizures, whose frequency was remarkably reduced post-operatively. The operation resulted in a major reduction of the psychiatric manifestations of pathological irritability, impulsiveness, epileptic cognitive dysfunction and the instability of abstraction capacity produced by affective impacts. Affective tenacity was ill affected by the surgical procedure, although a favourable effect was noticed. The presence of bilateral temporal foci did not decrease the efficacy of the surgical intervention, nor its effect on the seizures or the effect of surgery on the studied psychopathological changes.

Adolescent↗

PubMed2004

Cognitive changes in short-term hypothyroidism assessed with event-related brain potentials.

Hypothyroidism is a common clinical problem during (131)Iodine-therapy of thyroid cancer. In the present investigation, possible cognitive dysfunction during hypothyroid state was assessed by means of neuropsychological tests and the recording of event-related brain potentials (ERPs). Fifteen patients undergoing therapy for thyroid cancer were examined twice: (1) substituted with thyroid hormones, (2) during hypothyroid state immediately prior to treatment. Standard neuropsychological tests were applied during both sessions and subjects showed a mild-to-moderate impairment in their hypothyroid state. In addition, ERPs were recorded from 19 scalp sites while subjects performed two visual search tasks. The serial task required the effortful one-by-one scanning of several items within a visual array, while the parallel task allowed processing of all stimulus items in parallel and automatically. ERPs showed a marked amplitude decrement and delay of the P3 component known to index the speed of stimulus evaluation and the amount of available processing resources. This effect was present only for the serial search task, while no changes were seen in the parallel search task. These data show that hypothyroidism during (131)Iodine-therapy is associated with clinically relevant cognitive dysfunctions, especially with effortful attention demanding tasks.

Acute Disease↗

PubMed1983

Neuropsychological sequelae of postradiation somnolence syndrome.

Postirradiation somnolence syndrome in children with acute lymphocytic leukemia treated with cranial irradiation has been identified as a possible precursor of later cognitive dysfunction. To test this, the neuropsychological evaluation of 48 children who developed somnolence syndrome was compared with that of 31 children who did not have the syndrome at approximately 1 1/2 and 3 3/4 years after treatment. No differences in performance between the two groups were found on many measures of neuropsychological functioning with the exception of fine motor speed. Children without somnolence syndrome scored somewhat less than normal on measures of academic achievement. No other differences from normal performance were noted in either group. The results of the study indicated that if children with somnolence are at greater risk for the development of cognitive dysfunction than those not manifesting the syndrome, such risks occur at a time farther from treatment than 3 to 4 years.

Adolescent↗

PubMed2005

Anaesthesia in the older patient.

PURPOSE OF REVIEW: Clinical anaesthesia and analgesia address a growing number of elderly surgical patients. Ageing modifies physiology, pharmacokinetics and pharmacodynamics, and comorbidity is a common occurrence in the elderly. Therefore, based on recent information regarding perioperative outcome, indications and techniques should be individualized. RECENT FINDINGS: Clinical studies have highlighted the occurrence of postoperative cognitive dysfunction in elderly patients, and have given some information on its risk factors. As pain was found to be one of the most important of these, this review is also focused on the management of perioperative pain. Recently published studies have compared epidural analgesia and parenteral analgesics; others have described the handling of parenteral opioids for postoperative analgesia in elderly patients, and the opioid-sparing effect of multimodal analgesia. SUMMARY: Postoperative cognitive dysfunction (POCD) is quite frequent. If late POCD seemed not related to the type of anaesthesia and analgesia provided, early POCD (interval delirium) was found to be related to perioperative haematocrit and transfusion requirement and to postoperative pain. Epidural analgesia using local anaesthetics and/or opioids was found to be probably better than parenteral opioids for the control of postoperative pain and the prevention of postoperative morbidity and mortality. However, well implemented protocols of parenteral analgesics could be nearly as efficient.

Aged↗

PubMed2000

The role of depression severity in the cognitive functioning of elderly subjects with central nervous system disease.

OBJECTIVE: To examine the hypothesis that there is a causal relation between depression and cognitive dysfunction in patients with central nervous system (CNS) disease. DESIGN: Retrospective analysis of a clinical database. SETTING: Tertiary geriatric day hospital. PATIENTS: Sixty-five patients with depression and CNS disease, and 201 patients with depression but without CNS disease. OUTCOME MEASURES: Scores on the Hamilton Depression Rating Scale (Ham-D) and the Mattis Dementia Rating Scale (MDRS). RESULTS: A logistic regression analysis using MDRS status as the dependent variable, and a number of clinical variables as the predictor variables, showed that, in patients with CNS disease, only the Ham-D score predicted MDRS status (R = -0.19, p = 0.02). Ham-D score even more strongly predicted scores on a frontal system subtest of the MDRS (R = -0.262, p = 0.005). Ham-D score did not predict MDRS status in patients without CNS disease. Mean Mini Mental State Examination scores for the group with CNS disease were 25.1 at admission and 26.1 at discharge (p < 0.001). CONCLUSIONS: These findings suggest that depression contributes to frontal cognitive dysfunction in patients with CNS disease.

Aged↗

PubMed2003

Perioperative changes in cerebral blood flow after cardiac surgery: influence of anemia and aging.

BACKGROUND: Stroke occurs in 2% to 5% and cognitive dysfunction occurs acutely in 60% to 80% of patients early after cardiac surgery. Both may have long-term consequences. Research into mechanisms behind these sequelae has been focused intraoperatively, although there is little reason to believe that injury is limited to this period. Aging prominently increases the incidence of these sequelae. Anemia with cardiac surgery is acute and severe, should cause an increase in cerebral blood flow (CBF), and may impact stroke and cognitive function in this setting. To better understand changes in perioperative CBF physiology we have measured changes in CBF and the influence of anemia and aging on these changes. METHODS: Cerebral blood flow was measured using the noninvasive continuous arterial spin labeling perfusion magnetic resonance imaging method. Cerebral blood flow, mean arterial pressure, hemoglobin, hemoglobin oxygen saturation, and cardiopulmonary bypass time were recorded in 12 subjects before and 6 +/- 2 days after cardiac surgery. RESULTS: Cerebral blood flow increased from 44.6 +/- 15.6 mL100 g(-1)min(-1) to 64.4 +/- 20.1 mL100 g(-1)min(-1) after cardiac surgery, or 49.1% +/- 26.7%, (p < 0.0001). The absolute change in CBF (DeltaCBF) was predicted by the following regression model: DeltaCBF = -55 + 0.64(Age) + 0.53(CBF(Pre)) -3.3(DeltaHgb); R(2) = 0.81; p = 0.003, where CBF(Pre) is the baseline preoperative CBF and DeltaHgb is the change in hemoglobin from preoperative to postoperative periods. CONCLUSIONS: Cerebral blood flow increases after cardiac surgery, and anemia appears to be an important cause. Age appears also to be an important covariate, with advancing age further increasing the magnitude of this hyperemia. The interrelationship of aging and anemia, in determining perioperative changes in CBF, and potentially cerebral oxygenation, may have important implications for the understanding of perioperative stroke and cognitive dysfunction after cardiac surgery.

Adult↗

PubMed2002

Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats.

EuMil, is a herbal formulation comprising the standardised extracts of Withania somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Willd and Emblica officinalis Gaertn., all of which are classified in Ayurveda as rasayanas to promote physical and mental health, improve defense mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection to the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic and antistress activity of EuMil against chronic unpredictable, but mild, footshock stress-induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Panex ginseng (PG) was used for comparison. Gastric ulceration, plasma corticosterone levels, serum lipid, hepatic and renal functions were used as the stress indices. These effects were attenuated by EuMil (dose 100 mg/kg, p.o.) and PG (100 mg/kg. p.o.), administered once daily over a period of 14 days, the period of stress induction period. Further, chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural despair and cognitive dysfunction and immunosuppression. All these chronic stress-induced perturbations were attenuated, in a dose dependent manner by EuMil and PG. Thus, the results indicate that EuMil has significant adaptogenic and anti-stress, activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations, induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress. The likely contribution of the individual constituents of EuMil in the observed adaptogenic action of the polyherbal formulation, has been discussed.

Animals↗

PubMed1998

Prevalence of potentially reversible dementias and actual reversibility in a memory clinic cohort.

BACKGROUND: Although clinics for the evaluation of cognitive dysfunction have typically emphasized the detection and treatment of the reversible causes of dementia, it remains unclear whether the treatment of such causes results in reversal of the dementia. Therefore, the appropriate work-up for dementia is in dispute. METHODS: A chart review was performed with records from an urban tertiary care referral-based memory clinic. The records for 196 patients with dementia or suspected dementia, seen between October 1991 and December 1993, were examined to determine the prevalence of potentially reversible dementias and whether the cognitive dysfunction improved or resolved after treatment. Data abstracted from the medical charts included demographic information, medication use, presence of depression, and results of neuropsychological tests, blood work and neuroimaging. The clinical diagnosis, the response to treatment, if applicable, and the outcome (mean follow-up period 16 months) were analysed. The recommendations of the 1989 Canadian Consensus Conference on the Assessment of Dementia (CCCAD) on the use of CT were retrospectively applied in each case. RESULTS: Of the 196 patients, 45 (23.0%) had a potentially reversible condition identified by history, physical examination, blood testing or CT; in only 7 (3.6% of the total) did treatment result in improvement or resolution of the dementia. These 7 patients had higher results for the Mini-Mental State examination (mean result 26) and exhibited only mild cognitive deficits. Potentially reversible lesions were found in the CT scans of 6 (3.1%) patients: 4 had normal-pressure hydrocephalus and 2 had a brain tumour. If the CCCAD recommendations had been followed, CT would have been performed in 76 (38.8%) of the patients, and 1 of the 6 patients with a lesion would have been missed. INTERPRETATION: Both potential and actual reversibility of dementia was low in these memory clinic patients. The patients whose condition improved with intervention had early and milder cognitive deficits, which suggests that thorough evaluation of early memory loss is warranted.

Aged↗

PubMed2004

[Lowered VIQ level following traumatic brain injury].

A patient with traumatic brain injury (TBI) is often associated with incidence of cognitive dysfunction as a sequela. We have conducted WAIS-R to 237 patients who were diagnosed as TBI at the Kanagawa Rehabilitation Hospital in order to assess their intellectual function. Twelve patients, whose VIQ being marked significantly lower than PIQ, were retrospectively analyzed in terms of their Functional Independence Measure (FIM), neuropsychological test results and lesions found in diagnostic images. In consequence, presence of a patient group whose VIQ level is significantly lowered due to the TBI sequela is recognized, in addition to a finding that trauma sites of cerebral contusion or other incidents are not necessarily corresponding to the results of neuropsychological test. Furthermore, based on an observation that those patients with lowered VIQ level are also associated with aggravation of PIQ 'digit symbol', Trail Making Test, or word fluency levels. This result was before similar with the result of "32 cases of DAI (diffuse axonal injury)" which authors reported, and it was guessed anew that the main factor of a cognitive dysfunction was damage on axon.

Activities of Daily Living↗

PubMed2005

Correlation of midbrain diameter and gait disturbance in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Although gait disturbance is an important feature of idiopathic normal pressure hydrocephalus (NPH), only tentative theories have been offered to explain its pathophysiology. It has been suggested that the mesencephalic locomotor region is the anatomical substrate for the development of the hypokinetic NPH gait. To investigate this possibility, we evaluated the correlation between gait disturbance and midbrain diameter. METHODS: We enrolled 21 patients with NPH and 20 age-matched control subjects for the study. The maximal diameter of the midbrain and pons, and the width of the lateral and third ventricles were measured using midsagittal T1-weighted MRI and axial T2-weighted MRI, respectively. Gait disturbance, cognitive dysfunction, and incontinence were semiquantified. RESULTS: The maximal midbrain diameter was significantly smaller in the NPH group than in the controls (14.8 +/- 0.9 vs. 17.1 +/- 0.7 mm, p < 0.001). There were inverse correlations between the midbrain diameter and the widths of the two ventricles (r = -0.562, p = 0.008 for the third ventricle, and r = -0.510, p = 0.018 for the lateral ventricle). The severity of gait disturbance was negatively correlated with the midbrain diameter (r = -0.598, p = 0.004), but the degree of cognitive dysfunction and incontinence showed no significant correlation with midbrain diameter or ventricular width. CONCLUSIONS: This study suggests that midbrain atrophy is significantly associated with gait disturbance in NPH.

Aged↗

PubMed2001

[A patient with probable dementia with Lewy bodies, who showed improvement of dementia and parkinsonism by the administratim of donepezil].

We present a 73-year-old man with probable dementia with Lewy bodies(DLB). At 65 years of age, he gradually developed bradykinesia, gait disturbance and mild amnesia. At 71 years of age, he noted resting tremor in bilateral hands, and amnesia and disorientation were exacerbated. He was diagnosed as having parkinsonism and took L-dopa/carbidopa at 100 mg/day. Since he developed hallucination and abnormal behavior 2 days after the initiation of the drug, he stopped taking L-dopa and was admitted to our hospital. A neurological examination on admission revealed moderate amnesia, disorientation, finger agnosia, constitutional apraxia, mask-like face, cogwheel rigidity, resting tremor in bilateral hands, and bradykinesia. Brain MRI showed mild brain atrophy, and single photon emission computerized tomography(SPECT) showed diffuse moderate hypoperfusion in bilateral cerebral cortex. As he had fluctuating cognitive dysfunction and parkinsonism, he was diagnosed to have probable DLB. As his dementia was exacerbated by trihexyphenidyl, an anti-cholinergic agent, at 2 mg/day, we treated him with donepezil, an anti-choline esterase agent, at 3-5 mg/day. His parkinsonism, including rigidity and bradykinesia, was markedly improved his dementia, consisting of amnesia and disorientation. Electroencephalography (EEG) improved in the organization of the dominant rhythm. The SPECT improved in the blood perfusion of the bilateral frontal lobe as well as cognitive function and parkinsonism were maintained by donepezil for 6 months after discharge. A therapeutic efficacy of donepezil for DLB has recently been reported. It is notable that donepezil was beneficial not only for cognitive dysfunction but also for parkinsonism in the present case with probable DLB.

Aged↗

PubMedDate not supplied

Predictors of incident chronic widespread pain among veterans following the first Gulf War.

OBJECTIVE: We sought to determine the predictors of incident chronic widespread pain (CWP), specifically, the effect of preexisting symptoms, stress, and psychosocial factors in the subsequent development of CWP among veterans from the first Gulf War (GW). METHODS: We conducted a structured telephone survey (baseline) of military personnel originally from Iowa who were either eligible for or deployed to Operation Desert Shield/Desert Storm, approximately 5 years postconflict. We conducted a follow-up, clinical, in-person study of those who met a priori-defined outcomes of symptoms of cognitive dysfunction, depression, or CWP, and also a sample of those who did not meet any of the outcomes of interest. RESULTS: A total of 370 of 602 evaluated GW veterans were free of CWP 5 years postconflict. At follow-up, 69 (19%) of these had developed CWP. A positive family history of medically unexplained persistent symptoms [odds ratio (OR)=4.8 (2.3, 13.2)] was strongly associated with CWP. At baseline, individuals who reported preexisting symptoms of bronchitis [OR=4.9 (1.9, 12.3)] and cognitive dysfunction [OR=2.1 (1.1, 4.2)] were more likely to develop CWP. Alcohol use [OR=0.2 (0.1, 0.7)] was protective against CWP. Rather than combat-related exposure per se, the perception of stress at the time of the GW [OR=1.6 (1.1, 2.3)] correlated with CWP. DISCUSSION: Among the GW veterans evaluated longitudinally in this study, family history, predeployment symptoms, and the level of perceived stress during the GW were associated with subsequent development of CWP.

Adult↗

PubMed2005

Depressive symptom quality and neuropsychological performance in dementia.

BACKGROUND: It is unknown to what extent depression and cognitive dysfunction are related in subjects with dementia. A limitation of earlier studies is that only general measures of depression have been studied. METHODS: In a sample of 60 subjects with dementia according to DSM-III-R criteria depressive symptoms were divided into factors of mood and motivation disturbance according to a principal components analysis. Correlations were computed between the factor scores and the performance on a number of specific neuropsychological tests. As the symptom content of motivation disturbance suggests subcorticofrontal dysfunction it was hypothesized that this factor is related to impaired executive functions. RESULTS: 77% of the depressive symptoms contributed to the dimension of motivation disturbance and most of these symptoms occurred outside the context of a major depressive episode. Our hypothesis was supported by a significant negative correlation between motivation symptoms and semantic verbal fluency. This relationship seems to have specificity, as both the dimensions of mood symptoms and of general depressive symptoms did not correlate significantly with specific neuropsychological test scores. CONCLUSIONS: The division of depressive symptoms in factors of mood and motivation disturbance contributes to insight into the relationship between depression and cognitive dysfunction in dementia. An advantage of the motivation disturbance factor compared to the regular apathy scales is that it consists of depressive symptoms. Therefore, it becomes evident that apathy or impaired motivation may occur in patients with dementia both in and outside the context of a depressive syndrome.

Affective Symptoms↗

PubMed2005

Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997.

OBJECTIVE: Increasing survival of extremely low birth weight (ELBW; birth weight < 1000 g) infants raises a concern regarding the risks of adverse long-term outcome such as cognitive dysfunction. Few studies have reported long-term follow-up of representative regional cohorts. The objective of this study was to assess the 5-year outcome of a prospectively followed national ELBW infant cohort. METHODS: Of all live-born ELBW infants (n = 351) who were delivered in the 2-year period 1996-1997 in Finland, 206 (59%) survived until the age of 5 years. Of these, 103 were born at < 27 gestational weeks (GW). A total of 172 children were assessed with neurocognitive tests (Wechsler Preschool and Primary Scale of Intelligence-Revised and a Developmental Neuropsychological Assessment [NEPSY]). Nine children with cognitive impairment and inability to cooperate in testing were not assessed. Motor development was assessed with a modified Touwen test. RESULTS: The rate of cognitive impairment in the ELBW survivors was 9%. The rate of cerebral palsy was 14% (19% of ELBW infants who were born at < 27 GW). The mean full-scale IQ of the assessed children was 96 +/- 19 and in children of GW < 27 was 94 +/- 19. Attention, language, sensorimotor, visuospatial, and verbal memory values of NEPSY assessment were significantly poorer compared with normal population means. Four percent needed a hearing aid, and 30% had ophthalmic findings. Of 21 children who had been treated with laser/cryo for retinopathy of prematurity, 17 (81%) had abnormal ophthalmic findings. Of the whole cohort, 41 (20%) exhibited major disabilities, 38 (19%) exhibited minor disabilities, and 124 (61%) showed development with no functional abnormalities but subtle departures from the norm. Only 53 (26%) of the total ELBW infant cohort were classified to have normal outcome excluding any abnormal ophthalmic, auditory, neurologic, or developmental findings. Being small for gestational age at birth was associated with suboptimal growth at least until age 5. CONCLUSIONS: Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.

Child Development↗

PubMed2004

Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10).

Green tea catechins (GT-catechins) have been reported to have an antioxidative effect. We investigated the effect of long-term GT-catechin intake on aging and oxidative damage using aged mice with accelerated senescence (SAMP10), a model of brain senescence with cerebral atrophy and cognitive dysfunction. Major atrophy was observed in the rhinencephalon, hippocampus and striatum of 12-month-old untreated SAMP10 mice. Similarly, levels of 8-oxodeoxyguanosine (8-oxodG), a marker of oxidative DNA damage, were higher in these parts of the cerebrum than in the cerebral cortex and liver. GT-catechin intake effectively suppressed such atrophy in 12-month-old SAMP10 mice. A preventive effect of GT-catechin intake on oxidative DNA damage was also observed in the rhinencephalon (an area particularly susceptible to atrophy) at 6 months of age, i.e. during the early stages of atrophy. A suppressive effect of GT-catechin intake on cognitive dysfunction, as determined by the learning time needed to acquire an avoidance response and assessments of working memory in a Y-maze, was also found in 12-month-old mice. These results suggest that GT-catechin intake partially improves the morphologic and functional alterations that occur naturally in the brains of aged SAMP10 mice.

Aging↗