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Lack of the metabotropic glutamate receptor subtype 7 selectively impairs short-term working memory but not long-term memory.

Metabotropic glutamate receptors (mGluRs), and in particular the mGluR group III receptors (subtypes 4, 6, 7, 8) are known to play a role in synaptic plasticity and learning. Here, we report the effect of mGluR7 gene ablation in different learning paradigms. In the acoustic startle response (ASR), no differences were seen between knockout (KO) mice and wildtype (WT) littermates in parameters including prepulse inhibition and habituation. In an open field test, no differences were seen between genotypes in motor activity, exploratory behaviour, and fearful behaviour. In a T-maze reinforced alternation working memory (WM) task, again no difference was seen between groups. However, when increasing the demands on working-memory in a 4-arm and 8-arm maze task, KO mice committed more WM errors than WT littermates thereby uncovering a highly significant difference between the two groups that persisted every day for the whole 9 days of the experiment. In a 4-arm maze with 2 arms baited, KO and wildtype mice committed the same number of LTM errors, whereas KOs committed more WM errors. Altogether, these findings suggest that a lack of mGluR7 mainly impairs short-term working but not long-term memory performance while having no effect on sensorimotor processing, non-associative learning, motor activity and spatial orientation. The effects on WM are task-dependent and become apparent in more complex but not simple learning tasks. We discuss how mGluR7 could influence WM.

Animals↗

High level estradiol impairs and low level estradiol facilitates non-spatial working memory.

The present study investigated the effect of different doses of estradiol treatment on performance in the non-spatial delayed alternation T-maze a task in which performance is mediated by the integrity of the prefrontal cortex (PFC). Ovariectomized (OVX) female rats were injected with estradiol benzoate (0.3 microg/0.1 ml sesame oil (EB0.3), 5 microg/0.1 ml sesame oil (EB5) or 10 microg/0.1 ml sesame oil (EB 10)) or vehicle (sesame oil, 0.1 ml). Approximately 2 h after each injection, animals were trained daily on the T-maze with an initial delay of 10 s (short delay). Following a month with no treatment animals were re-trained at a 40 s delay (long delay). Days to reach criterion (one error per day for three consecutive days), mean total errors, errors across days, change in performance across training (short subtracted from long delay), and latency to reach goal arm, were scored. At the short delay, there was a weak effect for the low dose of estradiol (EB0.3 low-to-medium physiological) to significantly decrease the number of working memory errors compared to controls. However at the longer delay the higher doses of estradiol EB5 (high physiological) and to a lesser extent EB10 (suupraphysiological) significantly increased the number of working memory errors compared to controls. These data demonstrate the differential effect of estradiol during short and long delays on prefrontal cortex dependent working memory. High levels of estradiol impair PFC-dependent working memory at longer delays, while low level estradiol weakly facilitates PFC-dependent working memory at a shorter delay. These data suggest that estradiol's facilitatory effects on working memory may not be mediated through the PFC, while estradiols inhibitory effects on working memory may be mediated at least in part through the PFC.

Animals↗

Blockade of adenosine A2A receptors reverses short-term social memory impairments in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) exhibit impairment across several cognitive domains such as attention, short-term memory and spatial reference memory. These cognitive deficits have been variously attributed to disrupted dopaminergic, cholinergic and adenosinergic neurotransmitter function. However, social memory in SHR has not been investigated. In the present study, we therefore evaluated whether SHR exhibit altered short-term social memory abilities compared to normotensive Wistar rats (WIS) through two experimental paradigms (social recognition and habituation-dishabituation tests). We also compared the performance of SHR and WIS rats in the object recognition test. SHR exhibited significantly impaired performance in both models of social memory, but not in the object recognition test, demonstrating a selective deficit in the ability to recognize a juvenile rat after a short period of time. The administration of acute doses of the non-selective adenosine receptor antagonist caffeine (3.0 or 10.0 mg/kg, i.p.) and the adenosine A2A receptor antagonist 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-yl-amino]ethyl) phenol (ZM241385, 0.5 or 1.0 mg/kg, i.p.) but not the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1.0 or 3.0 mg/kg, i.p.) reversed this social memory impairment in SHR, but these treatments did not alter the hypertension state. These results demonstrate an impairment of short-term social memory in SHR and the involvement of the adenosine A2A receptors in this alteration.

Adenosine A2 Receptor Antagonists↗

Pharmacological characterization of the ameliorating effect on short-term memory impairment and antinociceptive effect of KT-90 in mice.

(-)-3-Acetyl-6beta-acetylthio-N-cyclopropylmethyl-normorphine (KT-90) is a synthesized compound that binds to mu-, delta- and kappa-opioid receptors in vitro. KT-90 induces analgesia in the tail-flick test and this effect is antagonized by nor-BNI, a selective kappa-opioid receptor antagonist. However, lower doses of KT-90 antagonize morphine-induced analgesia. We reported that kappa-opioid receptor agonists such as U-50,488H and dynorphin A (1-13), improved scopolamine-induced impairment of learning and memory in mice and/or rats. In this study, the effects of KT-90 were investigated in an acetic acid-induced writhing test and scopolamine-induced memory impairment test using spontaneous alternation performance in a Y-maze. Male ddY mice were treated with scopolamine (1.65 micromol/kg, s.c.) 30 min before the behavioral test. KT-90 (0.07-2.35 micromol/kg, s.c.) was injected 30 min before testing. In the writhing test, the antinociceptive effect of KT-90 (0.71 micromol/kg) was completely antagonized by a selective mu-opioid receptor antagonist, beta-funaltrexamine (10.2 nmol/mouse, i.c.v.) and partially antagonized by nor-BNI (4.9 nmol/mouse, i.c.v.), but it was not antagonized by a selective delta-opioid receptor antagonist, naltrindole (9.1 pmol/mouse, i.c.v.). KT-90 significantly improved the impairment of spontaneous alternation induced by scopolamine. The ameliorating effect of KT-90 was not antagonized by nor-BNI, but was almost completely antagonized by a selective sigma receptor antagonist, NE-100 (2.6 micromol/kg, i.p.). These results suggested that the KT-90-induced antinociceptive effect was mediated by mu- and partially by kappa-opioid receptors, and the KT-90-induced improvement in scopolamine-induced impairment of spontaneous alternation was mediated mainly via sigma receptors.

Animals↗

Supramammillary and adjacent nuclei lesions impair spatial working memory and induce anxiolitic-like behavior.

The present study assesses the involvement of the supramammillary and adjacent nuclei in spatial memory and anxiety-like behaviors. Rats with electrolytic lesions in the supramammillary nucleus were pre- and post-operatively trained in two spatial memory tasks and two anxiety tasks. Spatial memory tasks were performed in an open field with seven different goal positions containing the reward. Anxiety-like behaviors were tested in the elevated T-maze. In the spatial reference memory task, neither lesioned nor sham-lesioned groups were impaired. In the working memory task, lesioned animals were permanently impaired in their ability to solve the delayed-matching-to-position task. This working memory deficit is not related to increased proactive interference. It could be related to impairment of the rats ability to reorganize spatial stimuli. Consequently, rats were not able to achieve an optimal performance level to solve spatial tasks with continuous changes in the place location. In the elevated T-maze, lesioned rats reduced passive avoidance response but no changes in the escape response were observed. These results suggest a clear involvement of the supramammillary nucleus in working memory and behavioral inhibition but not in either spatial reference memory or in escape responses.

Analysis of Variance↗

Working memory in the Ts65Dn mouse, a model for Down syndrome.

This study used a matching-to-position schedule of reinforcement to examine working memory in Ts65Dn and littermate control mice. Initially there appeared to be a memory deficit in the Ts65Dn mice, which disappeared with extended practice. Thus, what appeared as a memory deficit may actually be the result of a delay in learning the concept of matching. These results suggest that delayed learning may be an important factor in other procedures examining working memory in Ts65Dn mice and have important implications for clinical treatment of Down syndrome patients.

Animals↗

Scopolamine and MK801-induced working memory deficits in rats are not reversed by CBD-rich cannabis extracts.

Smoking marijuana causes working and short-term memory deficits, an effect that is mediated by cannabinoid receptor (CB1) activation in the brain. While this may be due to the main psychoactive constituent Delta9-tetrahydrocannabinol (Delta9-THC), plant extracts also contain other cannabinoid and terpenoid compounds with unknown properties. Towards this end, we have recently shown that high concentrations of plant extracts rich in cannabidiol (CBD) can reverse working memory deficits induced by Delta9-THC which is a remaining contaminant of this extract [Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential effects of THC- and CBD-rich cannabis-extracts on working memory in rats. Neuropahrmacology 2004;47:1170-9]. Since this effect was dose-dependent and indicative of memory enhancing qualities of the CBD-rich extract, this prompted a wider investigation into the effects of CBD on other forms of amnesia in order to determine the mechanism of action and to reveal its potency against anticholinergic and antiglutamatergic agents. We employed a spatial delayed matching to position task in the open-field water maze. Both scopolamine (0.2 mg/kg i.p.) and dizocilpine (MK801: 0.1mg/kg i.p.) impaired working memory at delays of 30 s and 4 h. Two doses of CBD-rich extracts (5 and 10 mg/kg), which did not affect working memory when given alone, were unable to reverse these deficits when co-administered with scopolamine or MK801. These data suggest that reversal of working memory deficits by CBD-rich extracts are specific to the cannabinoid system and do not compensate for acutely induced cholinergic or glutamatergic receptor hypoactivity.

Analysis of Variance↗

Administration of raloxifene reduces sensorimotor and working memory deficits following traumatic brain injury.

Hormonal differences between males and females have surfaced as a crucial component in the search for effective treatments after experimental models of traumatic brain injury (TBI). Recent findings have shown that selective estrogen receptor modulators (SERMs) may have therapeutic benefit. The present study examined the effects of raloxifene, a SERM, on functional recovery after bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received injections of raloxifene (3.0mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min, 24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both sensorimotor (bilateral tactile removal and locomotor placing tests) and cognitive tests (reference and working memory in the Morris water maze). Raloxifene-treated animals showed a significant reduction in the initial magnitude of the deficit and facilitated the rate of recovery for the bilateral tactile removal test, compared to vehicle-treated animals. The raloxifene-treated animals also showed a significant improvement in the acquisition of working memory compared to vehicle-treated animals. However, raloxifene did not significantly improve the acquisition of reference memory or locomotor placing ability. Raloxifene treatment also did not result in a significant reduction in the size of the lesion cavity. Thus, the task-dependent improvements seen following raloxifene treatment do not appear to be the result of cortical neuroprotection. However, these results suggest that raloxifene improves functional outcome following bCCI and may present an interesting avenue for future research.

Analysis of Variance↗

Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism.

BACKGROUND: Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholism's effect on volumes of these structures has seldom been considered with in vivo measurement. METHODS: We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men. Six alcoholic subjects had been drinking recently, and 19 had been sober. RESULTS: Volumes of caudate and putamen were smaller in the alcoholics than in the control subjects, regardless of length of sobriety. Recent drinkers showed greater deficits in nucleus accumbens than sober alcoholics. Putamen volume was positively correlated with grip strength; MS/DB volume was positively correlated with verbal working memory independently of the negative association between age-standardized MS/DB and age in alcoholics. CONCLUSIONS: Caudate and putamen volume deficits occur and endure in chronic alcoholism. Nucleus accumbens might be especially sensitive to recent alcohol exposure. Striatal volumes should be considered in functional imaging studies of alcohol craving that target striatal brain regions. The age-alcohol interaction for MS/DB volumes is consistent with a cholinergic mechanism for the working memory impairment observed in the alcoholics.

Adult↗

Decreased encoding efficiency in schizophrenia.

BACKGROUND: Working memory deficits are a cardinal feature of schizophrenia that contribute to social and occupational dysfunction. METHODS: We used functional magnetic resonance imaging to compare the response to varying task demands during the performance of an item recognition task. Study design and analysis procedures were optimized for the detection of load dependent activity during the encoding phase of working memory. RESULTS: At the lowest load conditions the schizophrenia group performed as well as controls, however to achieve this equivalent performance the schizophrenia group had a significantly higher magnitude of activation compared to the controls. At the higher load conditions, the magnitude of activation between groups became more similar and we began to see performance deficits in the schizophrenic group. CONCLUSIONS: These results suggest that patients with schizophrenia have decreased efficiency in the cognitive processes that underlie the early encoding phase of this task. For lower demand tasks, patients with schizophrenia can compensate for decreased efficiency by working harder to achieve equivalent performance. Encoding utilizes attentional and perceptual cognitive operations that are likely common to many other cognitive tasks; therefore, inefficiency may underlie the deficits observed in a wide range of cognitive tasks in schizophrenia compared to healthy controls.

Adult↗

3,4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory.

BACKGROUND: +/-3,4-Methylenedioxymethamphetamine (MDMA) is a recreational drug that causes cognitive deficits in humans. A rat model for learning and memory deficits has not been established, although some cognitive deficits have been reported. METHODS: Male Sprague-Dawley rats were treated with MDMA (15 mg/kg x 4 doses) or saline (SAL) (n = 20/treatment group) and tested in different learning paradigms: 1) path integration in the Cincinnati water maze (CWM), 2) spatial learning in the Morris water maze (MWM), and 3) novel object recognition (NOR). One week after drug administration, testing began in the CWM, then four phases of MWM, and finally NOR. Following behavioral testing, monoamine levels were assessed. RESULTS: +/-3,4-Methylenedioxymethamphetamine-treated rats committed more CWM errors than did SAL-treated rats. +/-3,4-Methylenedioxymethamphetamine-treated animals were further from the former platform position during each 30-second MWM probe trial but showed no differences during learning trials with the platform present. There were no group differences in NOR. +/-3,4-Methylenedioxymethamphetamine depleted serotonin in all brain regions and dopamine in the striatum. CONCLUSIONS: +/-3,4-Methylenedioxymethamphetamine produced MWM reference memory deficits even after complex learning in the CWM, where deficits in path integration learning occurred. Assessment of path integration may provide a sensitive index of MDMA-induced learning deficits.

Analysis of Variance↗

Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure.

Maternally lead (Pb)-exposed, juvenile rats exhibit significant deficits in spatial reference memory acquisition and working memory performance in the Morris water maze (MWM). Acute systemic application of nicotine reverses these deficits without affecting behavioral performance of the age-matched, lead-unexposed control animals. These results suggest that nicotinic agonist treatments can ameliorate learning and memory impairments, presumably by compensating for deficient nicotinic function in developmentally lead-exposed animals.

Animals↗

Involvement of kappa-opioid receptors and sigma receptors in memory function demonstrated using an antisense strategy.

Although antinociceptive effects of U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulfonate and (-)-pentazocine have been reported to influence kappa-opioid receptors, the involvement of kappa-opioid receptors in learning and/or memory is still controversial. We have recently reported that the memory improving effect of (-)-pentazocine was antagonized by sigma1 receptor antagonist. In this study, we examined the effects of several antisense oligodeoxynucleotides (antisenses) to kappa1-opioid receptors and sigma1 receptor on memory and nociceptive function. Male ddY mice were treated subcutaneously (s.c.) with scopolamine (1.65 mumol/kg) and/or test drugs 30 min before a Y-maze test. U-50,488H significantly improved the scopolamine-induced impairment of spontaneous alternation behavior. Twenty micrograms of antisense targeting exons 2 and 3 of the kappa1-opioid receptor significantly reversed the effects of U-50,488H, but antisense targeting exon 1 and mismatch sense did not. The antisense targeting exon 3 was most effective. These antisenses themselves did not affect normal mice, indicating that kappa1-opioid receptors do not tonically regulate memory function. All three antisenses equally prevented U-50,488H-induced antinociceptive effects in the acetic-acid-induced writhing test. Pretreatment with antisense targeting sigma1 receptors (AS-sigma1) completely prevented the memory-improving effects of (-)- and (+)-pentazocine, although U-50,488H ameliorated the scopolamine-induced impairment of spontaneous alternation behavior in AS-sigma1-treated mice. These results suggest that kappa1-opioid receptors containing different exons have a distinct function in memory and nociceptive functions. Furthermore, kappa-opioid receptors agonist showing analgesic effects act on kappa-opioid receptors or sigma receptors and play important roles only when memory function is impaired, but the two neuronal systems regulate memory function independently.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against beta-amyloid toxicity.

Nicergoline, a drug used for the treatment of Alzheimer's disease and other types of dementia, was tested for its ability to protect neurons against beta-amyloid toxicity. Pure cultures of rat cortical neurons were challenged with a toxic fragment of beta-amyloid peptide (betaAP(25-35)) and toxicity was assessed after 24 h. Micromolar concentrations of nicergoline or its metabolite, MDL, attenuated betaAP(25-35)-induced neuronal death, whereas MMDL (another metabolite of nicergoline), the alpha1-adrenergic receptor antagonist, prazosin, or the serotonin 5HT-2 receptor antagonist, methysergide, were inactive. Nicergoline increased the basal levels of Bcl-2 and reduced the increase in Bax levels induced by beta-amyloid, indicating that the drug inhibits the execution of an apoptotic program in cortical neurons. In mixed cultures of rat cortical cells containing both neurons and astrocytes, nicergoline and MDL were more efficacious than in pure neuronal cultures in reducing beta-amyloid neurotoxicity. Experiments carried out in pure cultures of astrocytes showed that a component of neuroprotection was mediated by a mechanism of glial-neuronal interaction. The conditioned medium of cultured astrocytes treated with nicergoline or MDL for 72-96 h (collected 24 h after drug withdrawal) was neuroprotective when transferred to pure neuronal cultures challenged with beta-amyloid. In cultured astrocytes, nicergoline increased the intracellular levels of transforming-growth factor-beta and glial-derived neurotrophic factor, two trophic factors that are known to protect neurons against beta-amyloid toxicity. These results raise the possibility that nicergoline reduces neurodegeneration in the Alzheimer's brain.

Alzheimer Disease↗

Modest environmental enrichment: effect on a radial maze validation and well being of rats.

Our 8-arm radial maze test was validated to demonstrate memory deficits in rats treated with the muscarinic antagonist scopolamine hydro bromide (SHB, 0.1 mg/kg, i.p.). To improve quality of life, we enriched the environment of single housing rats. Enrichment procedures were chosen to increase the animals' well being without disturbing a lot the results of behavioural tests. It is modest, consisting of a plastic tube and corn chips. Enriched environment (EE) and Non-enriched Environment (NE) animals' performances were compared during the 8-arms radial maze validation. Enrichment procedures were chosen to increase the animals' well being without disturbing the results of behavioural tests. The impact of our enrichment conditions was then evaluated on the general behaviour of rats, weight evolution and results of a plus maze anxiety test. Results showed a deficit and a delay in learning for SHB-treated animals, and a general time-dependent learning effect, validating our test. No effect of enrichment on negative control animals was observed. For SHB-treated animals, enrichment increased performances during learning task and accentuated the deficits in test task. Exploratory behaviour of enriched animals seemed to be increased. A general amelioration of well being for EE animals was found (stable weight). We conclude that our enrichment allows increasing exploratory behaviour not modifying radial maze sensitivity using a simple modification of our protocol (limitation to 16 visits/trial). We decided to generalise this enrichment to all our studies, given its simplicity and obtained benefits.

Analysis of Variance↗

Verbal and spatial working memory in older individuals: A positron emission tomography study.

Recent reviews of a substantial number of studies have partially resolved questions concerning the brain regions used by working memory for manipulation and representation. We report a large single experiment in middle-aged to older adults (n = 89), classified by hypertensive status. Our design addresses the question of regions related to manipulation and representation, most particularly comparing spatial and verbal working memory. A control, memory search, and 2-back running memory task were performed with identical stimuli and responses during whole-brain 15O water positron emission tomography (PET) scans. Letter or spatial position instructions created verbal or spatial working memory versions of the tasks. We assessed agreement with the literature using regions of interest that were defined by clusters of activation empirically derived from the literature by Wager and Smith (Wager, T.D. and Smith, E.E., Neuroimaging studies of working memory: a meta-analysis, Cognitive, Affective and Behavioral Neuroscience, 3 (2003) 255-274). Our results largely confirmed conclusions from the review on the organization of working memory into dorsal prefrontal manipulation and ventrolateral prefrontal maintenance areas and representation in dorsal and ventral paths. Specific verbal versus spatial comparisons were also concordant with prior work establishing posterior lateralized representation for different contents by working memory. The similarity of results between this older sample and results derived by others from younger participants is notable.

Aged↗

Memory functions of children born with asymmetric intrauterine growth restriction.

OBJECTIVE: Learning difficulties are frequently diagnosed in children born with intrauterine growth restriction (IUGR). Models of various animal species with IUGR were studied and demonstrated specific susceptibility and alterations of the hippocampal formation and its related neural structures. The main purpose was to study memory functions of children born with asymmetric IUGR in a large-scale cohort using a long-term prospective paradigm. METHODS: One hundred and ten infants diagnosed with IUGR were followed-up from birth to 9 years of age. Their performance was compared with a group of 63 children with comparable gestational age and multiple socioeconomic factors. Memory functions (short-term, super- and long-term spans) for different stimuli types (verbal and visual) were evaluated using Visual Auditory Digit Span tasks (VADS), Rey Auditory Verbal Learning Test (Rey-AVLT), and Rey Osterrieth Complex Figure Test (ROCF). RESULTS: Children with IUGR had short-term memory difficulties that hindered both serial verbal processing system and simultaneous processing of high-load visuo-spatial stimuli. The difficulties were not related to prematurity, neonatal complications or growth catch-up, but were augmented by lower maternal education. Recognition skills and benefits from reiteration, typically affected by hippocampal dysfunction, were preserved in both groups. CONCLUSIONS: Memory profile of children born with IUGR is characterized primarily by a short-term memory deficit that does not necessarily comply with a typical hippocampal deficit, but rather may reflect an executive short-term memory deficit characteristic of anterior hippocampal-prefrontal network. Implications for cognitive intervention are discussed.

Child↗

Cognitive effects of atypical antipsychotics in patients with Alzheimer's disease and comorbid psychiatric or behavioral problems: a retrospective study.

BACKGROUND: In addition to cognitive decline, 30% to 40% of patients with Alzheimer's disease (AD) experience concomitant psychiatric and behavioral complications, such as hallucinations, delusions, and aggression. Atypical antipsychotics (AAs) are used to treat psychosis and aggressive behaviors in these patients; however, data regarding their early effects on cognition are conflicting. Based on a literature search, the cognitive effects of long-term treatment with AAs in outpatients with AD have not been studied. OBJECTIVE: The aim of this study was to describe and compare the rate of cognitive decline with longterm AA use in adult patients with AD receiving concomitant treatment with cholinesterase inhibitors. METHODS: This study was conducted at the Department of Neurology, The Ohio State University, Columbus, Ohio. Data were collected from the charts of adult outpatients who (1) received care at Memory Disorders Clinic, Columbus, Ohio, between April 2003 and June 2005; (2) were aged > or =55 years with a diagnosis of mild to severe definite or probable AD; (3) received an AA for > or =6 months or did not receive any AA; and (4) received a cholinesterase inhibitor during the entire evaluation period. Cognitive function, as measured using the Mini-Mental State Examination (MMSE), was compared between those who received AA treatment and those who did not. The end point was the rate of decline in cognitive function, defined as annualized change in mean MMSE score from baseline to the end of follow-up. RESULTS: Ninety-two outpatients were included in the final analysis (67 women, 25 men; mean age, 72.4 years). Thirty-four patients received treatment with an AA for 6 > or =months (mean duration of treatment, 421 days) and 58 did not receive any AA treatment. Quetiapine (mean dose, 67 mg/d) was prescribed to 28 (82 %) of the patients receiving an AA. The AAs were prescribed for psychosis (15 [44%] patients), psychosis/agitation (11 [32%]), and agitation/aggression (8 [24%]). The baseline mean MMSE scores in patients receiving and not receiving an AA were 14.65 and 17.88, respectively (P = 0.021), with mean (SD) annual rates of cognitive decline of 3.03 (1.84) and 2.24 (1.27), respectively (P = NS). CONCLUSION: The results from this retrospective study of data from a small, selected group of outpatients with AD did not find a significant difference in the rate of cognitive decline between those who received an AA for > or =6 months and those who did not.

Aged↗