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PubMed1976

Memory functions in depression.

In an attempt to elucidate the memory deficit in depression, short-term memory and long-term memory were examined by means of a memory test battery in 26 hospitalized depressed patients. Their performance was compared with a matched control group and with the performance of those 20 patients who improved after 26 days of treatment with antidepressants. Results indicate that depressed patients show marked impairment in short-term memory without an impairment in long-term memory. The greater the improvement of the clinical state, the greater the improvement in short-term memory, whereas long-term memory was not influenced by the therapeutic success.

Amitriptyline↗
PubMed1998

Effect of gender and apolipoprotein E genotype on response to anticholinesterase therapy in Alzheimer's disease.

BACKGROUND: Anticholinesterase therapies offer modest benefit to subgroups of AD sufferers. However, there has previously been no way of predicting which patients will respond to any of the drugs. OBJECTIVE: To discover if gender and/or apolipoprotein E genotype can be used as predictors of response in the clinical setting. DESIGN: 107 patients from the Bristol Memory Disorders Clinic took part in a double-blinded or open label trial of tacrine therapy for between 3 and 12 months or an open label trial of galanthamine therapy for 3 months. RESULTS: After 3 months of therapy, gender was found to be the only significant influence on the number of responders to anticholinesterase therapy. Men had a 73% greater chance of responding than women (p = 0.012). While ApoE genotype did not modify response to therapy in the short term, there are indications that it may affect response over the longer term (up to 12 months), and also that the initial advantage of male gender may not be maintained after 3 months. CONCLUSION: Gender is likely to be a more powerful determinant of outcome of anticholinesterase treatment than apolipoprotein E status in the short term.

Alzheimer Disease↗
PubMed1998

The behavioral pathology in Alzheimer's Disease Scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients.

OBJECTIVE: The aims of this study were to (a) determine the factor structure of the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), and (b) examine the associations of the observed factors to the level of cognitive impairment. DESIGN: Cross-sectional study of geriatric patients evaluated at an outpatient memory disorders clinic. SAMPLE: One hundred and fifty-one consecutive patients diagnosed with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria. RESULTS: Principal factors analysis with Varimax rotation resulted in a five-factor solution that accounted for 40.0% of the common variance. The factors included agitation/anxiety (agitation, anxiety of upcoming events; other anxiety), psychosis (delusions of theft, suspiciousness/paranoia; visual hallucinations), aggression (verbal aggressiveness; physical threats/violence; fear of being left alone; other delusions), depression (tearfulness; depressed mood) and activity disturbance (wandering; delusion one's house is not one's home). Several factors were associated with level of cognitive impairment as assessed by the Mini-Mental State Examination (MMSE). CONCLUSION: The results of this study suggest that the BEHAVE-AD measures a wide range of behavioral pathology that can be empirically represented by five independent symptom clusters among outpatient AD patients.

Activities of Daily Living↗
PubMed1999

Prevalence and correlates of Capgras syndrome in Alzheimer's disease.

OBJECTIVES: This study examined the prevalence and clinical correlates of Capgras syndrome (CS) in Alzheimer's disease. DESIGN: Cross-sectional study of elderly patients evaluated at an outpatient memory disorders clinic classified according to the presence or absence of CS. SUBJECTS: One hundred and fifty-one consecutive patients diagnosed with probable (N=110) or possible (N=48) Alzheimer's disease (AD) utilizing NINCDS-ADRDA diagnostic criteria. MATERIALS: The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Mini-Mental State Examination (MMSE) and Blessed Dementia Scale (BDS). RESULTS: CS was observed in 10% of the sample (N=16). Associated factors included other delusions, lower MMSE scores and higher BDS scores. The relation between CS and both cognitive and functional status remained significant after controlling for other delusions. CONCLUSION: CS was prevalent in approximately 10% of our community-dwelling AD sample. This syndrome was more common at the later stages of the illness and showed relations with increased functional impairment and other psychotic symptomatology.

Aged↗
PubMed2000

Vitamin B12 deficiency in dementia and cognitive impairment: the effects of treatment on neuropsychological function.

BACKGROUND: Vitamin B12 assay is part of the routine investigation of dementia, although few studies have investigated the effects of treatment on cognition. We examined the effects of B12 treatment on neuropsychological function and disease progression in patients presenting with dementia or cognitive impairment. METHODS: From 1432 patients who were assessed at the Bristol Memory Disorders Clinic, 125 patients with low serum B12 were identified. Sixty-six patients presenting with dementia, and 22 with cognitive impairment were seen for a second assessment after treatment. Changes in neuropsychological test scores were compared with those of patients with normal serum B12, matched by age and diagnosis. RESULTS: The majority of patients with low serum B12 had normal Hb and MCV values. We found no cases of reversible B12 deficiency dementia. The B12 treatment patients who presented with dementia showed no significant improvement, and no less deterioration, in their neuropsychological function than their matched group. However, a treatment effect was demonstrated among the patients presenting with cognitive impairment. These improved significantly compared to matched patients on the verbal fluency test (p<0.01). CONCLUSION: All patients with cognitive impairment should be investigated for B12 deficiency. Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia.

Aged↗
PubMed1978

The nature of deficit among paranoid and nonparanoid schizophrenics in the interpretation of sentences: an information processing approach.

Compared paranoid and nonparanoid schizophrenics to normal controls on a sentence verification task. The task permitted separation of times taken for central scanning and comparison operations and for operations associated with response selection and response execution. Neither group of schizophrenics took more time than normal controls for the latter operations; however, both groups of schizophrenics took longer at central scanning and comparison. Performance on this task was compared to previous results in which schizophrenics were similar to normals on times for central scanning and comparison, but took longer for non-central aspects of processing. It was condluded that the present deficit at the central processing level was attributable to deficient short-term memory of the encoded version of the sentence during the scanning and comparison operations. The absence of differences in the time taken for the non-central operations was ascribed to the exclusion of sentence encoding from the present latency times.

Adult↗
PubMed1985

Memory span and long-term memory deficits in brain-impaired patients.

Measures of verbal and visuospatial memory span and long-term memory were obtained from 21 brain-impaired and 21 neurologically unimpaired Veterans Administration medical patients. Significant deficits in both memory span and long-term memory were observed in the brain-impaired patients. Contrary to predictions from the experimental literature, memory span tests that require more processing of item content and location were not superior in detecting the memory span deficits. Discriminant function analyses revealed that measures of verbal and visuospatial long-term memory provided unique discrimination between the brain-impaired and unimpaired patients. However, when memory span measures were analyzed alone, inclusion of more than one measure of memory span did not provide additional unique discrimination. Implications for the clinical assessment of memory functioning are discussed.

Brain Damage, Chronic↗
PubMed1986

Semantic and visual memory after alcohol abuse.

This study compared the relative performance of 40 patients (M age = 31.7) with a history of alcohol abuse on tasks of short-term semantic and visual memory. Performance on the visual memory tasks was impaired significantly relative to the semantic memory task in a within-subjects analysis of variance. Semantic memory was unimpaired. This result is consistent with previous results obtained on tests of intelligence despite the added requirement of encoding, storing, and retrieving data inherent in the memory tasks. This result provides support for the contention that visuospatial and visuomotor skills evince primary residual impairment secondary to the abuse of alcohol. The significance of this result, in light of previous research, is discussed.

Adult↗
PubMed2000

Predictors of positive and negative appraisal among Cuban American caregivers of Alzheimer's disease patients.

OBJECTIVE: This study investigated predictors of positive (satisfaction) and negative (burden) appraisal among Cuban American (CA) caregivers of Alzheimer's disease (AD) patients. DESIGN: Cross-sectional study of AD patients and their family caregivers. SETTING: A university-affiliated outpatient memory disorders clinic. SUBJECTS: A convenience sample of 40 CA family caregivers of patients diagnosed with probable or possible AD according to NINCDS-ADRDA diagnostic criteria. MEASURES: AD patients: Mini-Mental State Examination (MMSE), Blessed Dementia Scale (BDS) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Caregivers: Caregiving Burden Scale (CBS), Caregiving Satisfaction Scale (CSS), Perceived Emotional Support scale (PES) and the Short Form-36 Health Survey-General Health Index (GH). RESULTS: Appraised burden was predicted by increased patient behavioral pathology, female caregiver gender and lower levels of perceived emotional support. The association between older caregiver age and increased burden approached significance. Older caregiver age and higher levels of perceived social support were shown to predict appraised satisfaction. Post-hoc analyses also indicated that length of residence in the United States, a measure of acculturation, was not associated with positive or negative appraisal. CONCLUSION: Appraised burden and satisfaction represent important outcomes of dementia care that show relations with distinct factors among CA caregivers. It is clear that further research is warranted in order to ascertain the relationship of ethnicity or culture to the process and psychological consequences of dementia caregiving. Continued investigations into predictors of caregiving satisfaction are also recommended.

Activities of Daily Living↗
PubMed2005

Cerebellar transcranial magnetic stimulation impairs verbal working memory.

Previous functional magnetic resonance imaging and patient studies indicate cerebellar participation in verbal working memory. In particular, event-related functional magnetic resonance imaging showed superior cerebellar activation during the initial encoding phase of the Sternberg task. This study used functional magnetic resonance imaging-guided transcranial magnetic stimulation (TMS) to test whether disruption of the right superior cerebellum (hemispheric lobule VI/Crus I) impairs verbal working memory performance. Single-pulse TMS was administered immediately after letter presentation during the encoding phase on half the trials. Sham TMS and a Motor Control task were included to test for general distraction and nonmemory-related motor effects. Results showed no effects of TMS on accuracy, but reaction times (RTs) on correct trials were significantly increased on TMS relative to non-TMS trials for the Verbal Working Memory and Motor Control tasks. Additional analyses showed that the increased RT was significantly greater for Verbal Working Memory than for the motor task, suggesting that the effect on working memory was not caused by interference with finger responses. Sham TMS did not affect RTs, indicating that the potentially distracting effects of the postencoding click did not contribute to the increase in RT. The observed effects from cerebellar disruption are consistent with proposed cerebrocerebellar involvement in verbal working memory.

Adolescent↗
PubMed1991

High-speed memory scanning in Parkinson's disease: adverse effects of levodopa.

High-speed memory scanning as assessed by the Sternberg paradigm was studied in 12 nondemented patients with fluctuating Parkinson's disease and 13 age-matched healthy controls. Patients were first assessed before taking their morning dose of levodopa ("off") and again after that dose had produced full clinical effect ("on") after that dose had produced full clinical effect ("on"). Although motor components of the measured choice reaction time were slower in patients when off than in control subjects, memory scanning speed was not different. After levodopa (on), patients' motor time normalized, but cognitive processing speed became significantly slower when compared with previous performance in the off condition and with controls. Contrary to previous concepts of bradyphrenia in patients with Parkinson's disease, these results indicate that dopaminergic stimulation can reduce cognitive processing speed.

Frontal Lobe↗
PubMed2004

Preservation of hippocampal neuron numbers and hippocampal subfield volumes in behaviorally characterized aged tree shrews.

Aging is associated with a decreased ability to store and retrieve information. The hippocampal formation plays a critical role in such memory processes, and its integrity is affected during normal aging. We used tree shrews (Tupaia belangeri) as an animal model of aging, because in many characteristics, tree shrews are closer to primates than they are to rodents. Young and aged male tree shrews performed a holeboard spatial memory task, which permits assessment of reference and working memory. Upon completion of the behavioral measurements, we carried out modified stereological analyses of neuronal numbers in various subdivisions of the hippocampus and used the Cavalieri method to calculate the volumes of these subfields. Results showed that the working memory of aged tree shrews was significantly impaired compared with that of young animals, whereas the hippocampus-dependent reference memory remained unchanged by aging. Estimation of the number of neurons revealed preserved neuron numbers in the subiculum, in the subregions CA1, CA2, CA3, and in the hilus of the dentate gyrus. Volume measurements showed no aging-related changes in the volume of any of these hippocampal subregions, or in the molecular and granule cell layers of the dentate gyrus of tree shrews. We conclude that the observed changes in memory performance in aging tree shrews are not accompanied by observable reductions of hippocampal neuron numbers or hippocampal volume, rather, the changes in memory performance are more likely the result of modified subcellular mechanisms that are affected by the aging process.

Aging↗
PubMed2004

Patient versus informant perspectives of Quality of Life in Mild Cognitive Impairment and Alzheimer's disease.

BACKGROUND: Prior studies on Quality of Life (QOL) in Alzheimer's disease (AD) have rarely included control participants, or participants with very mild levels of cognitive impairment. Furthermore, there is little data to indicate whether or not mildly impaired patients can provide self-report QOL data or if informant reports are needed. OBJECTIVES: This study compared QOL ratings from informants and patients with mild AD (n = 26), Mild Cognitive Impairment (MCI, n = 30), and elderly controls (n = 23). METHODS: Participants (aged 60-91 years) were recruited from an outpatient memory disorder clinic. Elderly controls were recruited from the community. Measures about patients were the Dementia Quality of Life scale, the Neuropsychiatric Inventory-Questionnaire, Instrumental of Activities of Daily Living, and Mini-mental State Exam. Informant depression was assessed with the Geriatric Depression Scale. RESULTS: Results indicated that overall patient-informant agreement for MCI (M=0.24), AD (M=0.48), and controls (M=0.49) did not differ significantly. Self-reported QOL did not differ significantly across the 3 groups. For caregiver-reports, QOL in MCI again did not differ from controls but was significantly greater than QOL in AD for 2 of 6 scales, and QOL in controls was greater than AD for 4 of 6 scales. Regression analyses indicated that neuropsychiatric symptoms were the most consistent predictors of QOL. CONCLUSIONS: In summary, informant- and self-perceptions of QOL differed substantially. Results suggest that future investigators should carefully consider gathering QOL information from both informants and patients because they provide unique information regarding patient QOL and, to date, neither source of information has been established to be superior.

Aged↗
PubMed2005

Conceptualization and measurement of getting lost behavior in persons with early dementia.

BACKGROUND: The primary purpose of this preliminary research was to describe the psychometric properties of a newly-developed Everyday Spatial Questionnaire for Dementia-patient version (ESQD-P) in a Chinese population. A secondary goal was to assess the relationship between executive functions and wayfinding strategy application. The ESQD-P is a measure for the phenomenon of 'getting lost behavior' (GLB) reported by early Alzheimer's disease sufferers, based on the concept of spatial problem-solving. METHODS: With a cross-sectional descriptive design, the ESQD-P was validated by examining for internal consistency, construct validity, concurrent validity, and exploratory factor analyses among 116 outpatients in the memory disorder clinic of a veterans' general hospital in Taiwan. Other variables included were: global cognition, measured by the Cognitive Abilities Screening Instrument; stages of dementia, measured by the Clinical Dementia Rating Scale; and depressive symptoms, measured by the Geriatric Depression Scale-Short Form. RESULTS: Findings indicated that the Chinese ESQD-P is a reliable instrument for measuring GLB (internal consistency alpha = 0.73). A five-factor solution explained 55.45% of the score variance, while the correlations between the patient and proxy versions of this instrument yielded an acceptable concurrent validity. Executive functions can predict both global and analytic wayfinding strategies. CONCLUSIONS: GLB may be explained in part by declining executive functions. Deleting the coping strategies subscale may improve psychometric properties of the ESQD-P.

Aged↗
PubMed2006

Cognitive decline and survival in Alzheimer's disease.

OBJECTIVE: To test the association of rate of cognitive decline, an indicator of the severity of the underlying disease process, with risk of death in Alzheimer's disease (AD). METHODS: A total of 472 persons with clinically diagnosed AD were recruited from a memory disorders clinic and day care centers in the Chicago area. They completed a uniform clinical evaluation at baseline and a battery of nine cognitive tests at six-month intervals for a mean of about three years. A previously established measure of global cognition was derived from the nine tests. RESULTS: During follow-up, 168 persons (36%) died. In a proportional hazards model that controlled for age, sex, race, education, and baseline level of cognition, individual rate of global cognitive decline, estimated with least squares regression, was linearly related to mortality risk. Thus, a person declining minimally (increase of 0.04 unit per year, 90th percentile) was 2.7 times less likely to die during the study period than a person declining rapidly (decrease of 0.76 unit per year, 10th percentile). Controlling for baseline disability did not substantially affect results. The association of cognitive decline with mortality was substantially stronger for white persons compared to African Americans and in those with less compared to more education. CONCLUSION: The results indicate that the rate at which cognition declines in AD is robustly related to survival.

Adult↗
PubMed2004

Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice.

Synaptotagmin IV (Syt IV) is an activity-inducible, secretory vesicle protein that is thought to function as an inhibitor of neurotransmitter release (Littleton et al. Nature 400:757-760, 1999). To test this hypothesis in neurons of the mammalian CNS, we measured field excitatory postsynaptic potentials (fEPSPs) in hippocampal slice preparations from Syt IV (-/-) mice. At Schaffer collateral synapses, the basal properties of neurotransmission are largely normal. However, two forms of short-term plasticity, paired-pulse facilitation (PPF) and post-tetanic potentiation (PTP), are significantly enhanced in area CA1 of Syt IV (-/-) slices. Similarly, the early stages of long-term potentiation (LTP) are also enhanced at these synapses. Consistent with the low levels of Syt IV observed in dentate granule cells, the mossy fiber synapses in Syt IV (-/-) slices display largely normal PPF and LTP. In addition, we find that Syt IV (-/-) mice have deficits in the associative passive avoidance memory paradigm, but are normal in the novel object recognition paradigm. The synaptic architecture and connectivity of Syt IV (-/-) brains is indistinguishable from wild-type mice as indicated by immunohistochemical analysis. These results suggest Syt IV is a presynaptic negative regulator of short-term plasticity in area CA1 of the hippocampus and is required for some, but not all, forms of hippocampus-dependent memory.

Animals↗
PubMed2005

Functional connectivity with the hippocampus during successful memory formation.

Although it is well established that the hippocampus is critical for episodic memory, little is known about how the hippocampus interacts with cortical regions during successful memory formation. Here, we used event-related functional magnetic resonance imaging (fMRI) to identify areas that exhibited differential functional connectivity with the hippocampus during processing of novel objects that were subsequently remembered or forgotten on a postscan test. Functional connectivity with the hippocampus was enhanced during successful, as compared with unsuccessful, memory formation, in a distributed network of limbic cortical areas-including perirhinal, orbitofrontal, and retrosplenial/posterior cingulate cortex-that are anatomically connected with the hippocampal formation. Increased connectivity was also observed in lateral temporal, medial parietal, and medial occipital cortex. These findings demonstrate that successful memory formation is associated with transient increases in cortico-hippocampal interaction.

Adult↗