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PubMed1987

Dementia following strokes in the mesencephalon and diencephalon.

Six patients had ischemic infarcts in the paramedian thalamic, subthalamic, and mesencephalic areas. In addition to ocular motility problems, ataxia, dysmetria, and mild pyramidal signs, there were consistent behavioral observations and neuropsychological findings. All of the patients had initial deficits in arousal, and gradually improved to normal wakefulness. When awake, all of the patients had impaired attention, mental control, and slowed verbal and motor responsiveness. They were apathetic, poorly motivated, and affect was flat or occasionally labile. All of the patients had a memory disorder characterized by anterograde and retrograde loss. One patient had significant language impairment. These deficits persisted in all but one patient who had a predominantly mesencephalic lesion. We believe the cluster of findings in these patients constitutes a characteristic syndrome of dementia related to paramedian mesencephalic and diencephalic infarcts. This syndrome bears close resemblance to that associated with some subcortical degenerative disorders such as progressive supranuclear palsy. In cases of paramedian mesencephalic and diencephalic infarcts, however, computed tomography and magnetic resonance imaging can delineate clinicoanatomic relationships that account for specific constituents of the syndrome.

Adult↗
PubMed1989

Predominant left hemisphere metabolic dysfunction in dementia.

Thirty-one patients with probable Alzheimer's disease and 11 patients with memory disorders, attributable to multiple cerebral infarctions, were studied using 18-F-fluorodeoxyglucose-positron emission tomography scans. Asymmetry in cerebral glucose metabolism within these diagnostic groups was assessed by comparison with the metabolic rates obtained in age-equivalent healthy control subjects. A significantly greater number of individuals in both patient groups exhibited predominant left rather than right hemisphere hypometabolism. In addition, for patients with Alzheimer's disease, the degree of asymmetry was not related to either the severity or duration of dementia. These findings could be explained by greater susceptibility of the left hemisphere to degenerative or ischemic brain disease, by a specific sampling effect, or most likely, by greater metabolic deficits resulting from left rather than right hemisphere impairment.

Brain↗
PubMed1992

Immediate and delayed prose recall among normal and demented adults.

The Logical Memory subtest of the Wechsler Memory Scale (Form I) was administered as part of a battery of tests to 64 subjects without dementia and 51 with very mild dementia. The demented group's immediate and delayed recall was significantly impaired relative to the control group. Immediate and delayed scores were highly correlated in both groups. Hierarchical multiple-regression analyses revealed that dementia classification did not significantly predict delayed recall performance above and beyond immediate recall performance. This suggests that, in its early stages, dementia primarily affects the encoding of prose material.

Aged↗
PubMed1994

Screening for cognitive impairment in older individuals. Validation study of a computer-based test.

OBJECTIVE: This study examined the validity of a computer-based cognitive test that was recently designed to screen the elderly for cognitive impairment. DESIGN: Criterion-related validity was examined by comparing test scores of impaired patients and normal control subjects. Construct-related validity was computed through correlations between computer-based subtests and related conventional neuropsychological subtests. SETTING: University center for memory disorders. PARTICIPANTS: Fifty-two patients with mild cognitive impairment by strict clinical criteria and 50 unimpaired, age- and education-matched control subjects. Control subjects were rigorously screened by neurological, neuropsychological, imaging, and electrophysiological criteria to identify and exclude individuals with occult abnormalities. RESULTS: Using a cut-off total score of 126, this computer-based instrument had a sensitivity of 0.83 and a specificity of 0.96. Using a prevalence estimate of 10%, predictive values, positive and negative, were 0.70 and 0.96, respectively. Computer-based subtests correlated significantly with conventional neuropsychological tests measuring similar cognitive domains. Thirteen (17.8%) of 73 volunteers with normal medical histories were excluded from the control group, with unsuspected abnormalities on standard neuropsychological tests, electroencephalograms, or magnetic resonance imaging scans. CONCLUSIONS: Computer-based testing is a valid screening methodology for the detection of mild cognitive impairment in the elderly, although this particular test has important limitations. Broader applications of computer-based testing will require extensive population-based validation. Future studies should recognize that normal control subjects without a history of disease who are typically used in validation studies may have a high incidence of unsuspected abnormalities on neurodiagnostic studies.

Aged↗
PubMed1994

Discrimination between stages of Alzheimer's disease with subsets of Mini-Mental State Examination items. An analysis of Consortium to Establish a Registry for Alzheimer's Disease data.

OBJECTIVE: To identify minimal sets of Mini-Mental State Examination (MMSE) items that can distinguish normal control subjects from patients with mild Alzheimer's disease (AD), patients with mild from those with moderate AD, and those with moderate from those with severe AD. DESIGN: Two randomly selected equivalent half samples. Results of logistic regression analysis from data from the first half of the sample were confirmed by receiver operating characteristic curves on the second half. SETTING: Memory disorders clinics at major medical centers in the United States affiliated with the Consortium to establish a Registry for Alzheimer's Disease (CERAD). PARTICIPANTS: White, normal control subjects (n = 412) and patients with AD (n = 621) who met CERAD criteria; nonwhite subjects (n = 165) and persons with missing data (n = 27) were excluded. MAIN OUTCOME MEASURES: Three four-item sets of MMSE items that discriminate, respectively, (1) normal controls from patients with mild AD, (2) patients with mild from those with moderate AD, and (3) patients with moderate from those with severe AD. RESULTS: The MMSE items discriminating normal controls from patients with mild AD were day, date, recall of apple, and recall of penny; those discriminating patients with mild from those with moderate AD were month, city, spelling world backward, and county, and those discriminating patients with moderate from those with severe AD were floor of building, repeating the word table, naming watch, and folding paper in half. Performance on the first two four-item sets was comparable with that of the full MMSE; the third set distinguished patients with moderate from those with severe AD better than chance. CONCLUSIONS: A minimum set of MMSE items can effectively discriminate normal controls from patients with mild AD and between successive levels of severity of AD. Data apply only to white patients with AD. Performance in minorities, more heterogeneous groups, or normal subjects with questionable cognitive status has not been assessed.

Aged↗
PubMed1995

The age at onset of Alzheimer's disease and an intracranial area measurement. A relationship.

OBJECTIVE: To examine the possibility that premorbid brain size may influence the age at onset of symptoms of Alzheimer's disease (AD). DESIGN: Retrospective case series. SETTING: Outpatients attending a memory disorders clinic in a tertiary referral center. PATIENTS: Twenty-eight female patients with the diagnosis of probable AD, selected for the availability of informant derived estimates of age at onset of symptoms and computed tomographic scans of the head satisfying angulation criteria. MAIN OUTCOME MEASURE: An average intracranial area of two adjacent computed tomographic scan sections appropriately angled was used as a correlate of premorbid brain size. Strict intracranial volume measurement was not performed. RESULTS: Age at onset of symptoms of AD correlated positively (r = .48, P = .009) with our measure of premorbid brain size. There was no confounding by education, height, or ethnicity. CONCLUSION: Premorbid brain size may be an important determinant of the age at onset of symptoms of AD. Epidemiologic studies of AD may need to assess the relationship between brain size and putative risk factors, eg, low educational attainment, since there is evidence that brain size is not distributed uniformly across populations.

Age of Onset↗
PubMed1995

Plasma and red blood cell thiamine deficiency in patients with dementia of the Alzheimer's type.

OBJECTIVES: To determine the prevalence of plasma thiamine deficiency in patients referred to a memory disorder clinic and to compare plasma thiamine levels with red blood cell (RBC) thiamine levels. To determine if patients with senile dementia of the Alzheimer's type (SDAT) differ from those without SDAT in either plasma or RBC thiamine levels. DESIGN: Case-control study. SETTING: Ambulatory care referral center. PATIENTS: Consecutive sample of 34 patients; 17 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and 17 patients with other forms of dementia. METHODS: Plasma and RBC thiamine levels were determined in all patients with the use of a microbiologic assay known for its specificity to biological forms of thiamine. Vitamin supplementation was determined by chart review. OUTCOME MEASURES: Plasma and RBC thiamine levels. RESULTS: Patients with SDAT were found to have significantly lower plasma thiamine levels than patients without SDAT. Low plasma thiamine levels were detected in a significantly larger proportion of patients with SDAT than in patients without SDAT. Red blood cell thiamine levels did not correlate with the clinical diagnosis of SDAT. Vitamin supplementation did not correlate with diagnosis and plasma or RBC thiamine levels. CONCLUSIONS: A significant proportion of patients with SDAT may have a thiamine deficiency, which may have an impact on cognitive function. Currently used assays may not be adequate to assess thiamine status.

Aged↗
PubMed1998

A 7 minute neurocognitive screening battery highly sensitive to Alzheimer's disease.

OBJECTIVE: To determine the validity and reliability of a rapidly administered neurocognitive screening battery consisting of 4 brief tests (Enhanced Cued Recall, Temporal Orientation, Verbal Fluency, and Clock Drawing) to distinguish between patients with probable Alzheimer's disease (AD) and healthy control subjects. SUBJECTS: Sixty successive referrals to the Memory Disorders Clinic at Southwestern Vermont Medical Center, Bennington, who were diagnosed as having probable AD and 60 community-dwelling volunteers of comparable age, sex distribution, and education. DESIGN: Interrater and test-retest reliability, intergroup comparisons between patients with AD and control subjects on the 4 individual tests, and determination of probability of dementia for patients with AD and control subjects using the entire battery of tests. SETTING: Outpatient care. MAIN OUTCOME MEASURE: Comparison of the probability of dementia on the 7 Minute Screen with the criterion standard of clinical diagnosis established by examination and laboratory studies. SECONDARY OUTCOME MEASURES: Test-retest and interrater reliability (correlation coefficients), time for administration. RESULTS: Mean time of administration was 7 minutes 42 seconds. Mean scores for patients with AD and control subjects on all 4 individual tests were significantly different (for each, P<.001). When the 4 tests were combined in a logistic regression, the battery had a sensitivity of 100% and a specificity of 100%. A series of 1000 repeated random samples of 30 patients with AD and 30 control subjects taken from the overall sample of 60 patients with AD and 60 control subjects had a mean sensitivity of 92% and a mean specificity of 96%. The battery was equally sensitive to patients with mild AD as demonstrated by correctly classifying all 13 patients with AD using Mini-Mental State Examination scores of 24 or higher. Neither age nor education was a statistically significant factor when added as a covariate. Test-retest reliabilities for individual tests ranged from 0.83 to 0.93. Test-retest reliability for the entire battery was 0.91. Interrater reliability for the entire battery was 0.92. CONCLUSIONS: The 7 Minute Screen appears highly sensitive to AD and may be useful in helping to make initial distinctions between patients experiencing cognitive changes related to the normal aging process and those experiencing cognitive deficits related to dementing disorders such as AD. It has reasonable interrater and test-retest reliability, can be administered in a brief period, and requires no clinical judgment and minimal training.

Aged↗
PubMed2002

Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease.

BACKGROUND: The isoprostane 8,12-iso-iPF(2alpha)-VI, a specific marker of in vivo lipid peroxidation, is increased in Alzheimer disease (AD). The pathological changes associated with AD have a long silent phase before the appearance of clinical symptoms. Several studies have shown that AD is preceded by a prodromal phase characterized by mild cognitive impairment (MCI). OBJECTIVE: To investigate levels of this biomarker in subjects with MCI. DESIGN AND MAIN OUTCOME MEASURES: Using gas chromatography-mass spectrometry analysis, we measured 8,12-iso-iPF(2alpha)-VI levels in urine, plasma, and cerebrospinal fluid of patients with AD, subjects with MCI, and cognitively normal elderly subjects. SETTING AND PATIENTS: Subjects attending the Memory Disorders Clinic. RESULTS: We found significantly higher 8,12-iso-iPF(2alpha)-VI levels in cerebrospinal fluid, plasma, and urine of subjects with MCI compared with cognitively normal elderly subjects. CONCLUSIONS: These results imply that individuals with MCI have increased brain oxidative damage before the onset of symptomatic dementia. Measurement of this isoprostane may identify a subgroup of patients with MCI with increased lipid peroxidation who are at increased risk to progress to symptomatic AD.

Adult↗
PubMed2003

Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism.

BACKGROUND: CYP46, the gene encoding cholesterol 24-hydroxylase, plays a key role in the hydroxylation of cholesterol and thereby mediates its removal from brain. OBJECTIVE: To study the association of polymorphic sites on CYP46 with Alzheimer disease (AD) traits and with the risk of the development of AD. DESIGN: Alzheimer disease traits (beta-amyloid load, beta-amyloid peptides, hyperphosphorylated tau protein) were assessed in brain tissues and in the cerebrospinal fluid of patients with AD and control subjects. Genetic associations were studied in 2 independent populations. SETTING: Specialized centers for memory disorders in Switzerland, Greece, and Italy. PARTICIPANTS: Fifty-five brain tissues from nondemented elderly patients for the histopathological studies; 38 patients with AD and 25 control subjects for the cerebrospinal fluid studies; 201 patients with AD and 248 control subjects for the genetic association studies. RESULTS: A polymorphism of CYP46 was associated with increased beta-amyloid load in brain tissues as well as with increased cerebrospinal fluid levels of beta-amyloid peptides and phosphorylated tau protein. Moreover, this CYP46 polymorphism was associated with higher risk of late-onset sporadic AD in 2 independent populations (odds ratio, 2.16; 95% confidence interval [CI], 1.41-3.32; P<.001). The additional presence of 1 or 2 apolipoprotein E epsilon4 alleles synergistically increased the risk of AD to an odds ratio of 9.6 (95% CI, 4.9-18.9; P<.001) as compared with 4.4 for apolipoprotein E epsilon4 alone (95% CI, 2.8-6.8; P<.001). CONCLUSION: CYP46 influences brain beta-amyloid load, cerebrospinal fluid levels of beta-amyloid peptides and phosphorylated tau, and the genetic risk of late-onset sporadic AD.

Age of Onset↗
PubMed2005

Different patterns of magnetic resonance imaging atrophy for frontotemporal lobar degeneration syndromes.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is an uncommon degenerative dementia that presents with focal cognitive and behavioral deficits. OBJECTIVE: To determine the correlation of the different presentations of FTLD with structural neuroimaging findings. DESIGN AND PATIENTS: In a blinded study, we retrospectively evaluated the clinical presentations and magnetic resonance imaging (MRI) patterns of atrophy in 59 patients with FTLD and 26 patients with probable Alzheimer disease at a memory disorders clinic. RESULTS: Analysis of variance revealed a significant difference in the patterns of atrophy in the FTLD and Alzheimer disease groups. Patients with FTLD presenting with altered personal conduct had significant bifrontal atrophy, whereas patients presenting with semantic dementia had significant left temporal and bifrontal atrophy compared with other groups. Disinhibited behavior and hyperphagia correlated with right frontal atrophy, and fluent, anomic aphasia correlated with left temporal atrophy. CONCLUSIONS: We found that the type of clinical presentation of FTLD correlates with specific areas of atrophy. Our method of analysis may be useful to elicit further anatomic-behavioral relationships in degenerative brain disorders.

Aged↗
PubMed2005

Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men.

CONTEXT: There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD). OBJECTIVE: To evaluate the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with mild AD and healthy elderly men. DESIGN: Twenty-four-week, randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles, San Francisco, and Irvine. PATIENTS OR OTHER PARTICIPANTS: Sixteen male patients with AD and 22 healthy male control subjects. Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics. INTERVENTION: Testosterone and placebo, in the form of hydroalcoholic gel (75 mg), were applied daily to the skin of the participants. MAIN OUTCOME MEASURES: Instruments assessing cognitive functioning (Alzheimer's Disease Assessment Scale-Cognitive Subscale, California Verbal Learning Test, Block Design Subtest, Judgment of Line Orientation, Developmental Test of Visual-Motor Integration), neuropsychiatric symptoms (Neuropsychiatric Inventory), global functioning (Clinician's Interview-Based Impression of Change), and quality of life (Quality of Life-Alzheimer Disease Scale). RESULTS: For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale (P = .01). No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo. In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group (P = .09) compared with placebo treatment. No difference between the treatment groups was detected in the remaining outcome measures. Testosterone treatment was well tolerated with few adverse effects relative to placebo. CONCLUSIONS: Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD. Testosterone had minimal effects on cognition.

Affect↗
PubMed2007

The metabolic syndrome and Alzheimer disease.

BACKGROUND: The metabolic syndrome is a risk factor for cardiovascular diseases, which have been linked to Alzheimer disease. However, a link between Alzheimer disease and the metabolic syndrome has not yet been established. OBJECTIVE: To investigate the relationship between the metabolic syndrome and Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 50 consecutive patients diagnosed with probable Alzheimer disease from the Memory Disorders Clinics, Launceston, Australia, and Bristol, England, and 75 cognitively normal controls. MAIN OUTCOME MEASURES: The odds ratio of the metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III. RESULTS: Compared with controls, patients with Alzheimer disease had a significantly larger mean waist circumference, higher mean plasma concentrations of triglycerides and glucose, and a lower mean plasma concentration of high-density lipoprotein cholesterol, but they had lower mean systolic blood pressure. The metabolic syndrome was associated with Alzheimer disease (odds ratio, 3.2; 95% confidence interval, 1.2-8.4; P = .02), and this association was strengthened when the hypertension component was excluded (odds ratio, 7.0; 95% confidence interval, 2.7-18.3; P < .001). All of the analyses were adjusted for age, sex, and location. CONCLUSIONS: This study suggests that Alzheimer disease is associated with the metabolic syndrome. This could have implications for the prevention and treatment of Alzheimer disease.

Aged↗
PubMed1989

Short-term memory impairment in cannabis-dependent adolescents.

The concentration of delta-9-tetrahydro-cannabinol in marijuana available in the United States has increased by 250% since investigations of the effects of marijuana on short-term memory first appeared in scientific journals. Moreover, previous investigations of short-term memory in long-term marijuana smokers involved adults only. We evaluated the auditory/verbal and visual/spatial memory of 10 cannabis-dependent adolescents and compared the results with performance of 17 subjects in two control groups. The control groups included 8 adolescent drug abusers who had not been long-term users of cannabis and another 9 adolescents who had never abused any drug. All three groups were matched on age, IQ, and absence of previous learning disabilities. Adolescents with a history of frequent alcohol or phencyclidine abuse were excluded from entering the study. A battery of seven neuropsychological tests was administered initially to all subjects and a parallel test battery was administered 6 weeks thereafter. Significant differences between the cannabis-dependent group and the two control groups were obtained initially on the Benton Visual Retention Test (F[2,24] = 6.07) and the Wechsler Memory Scale Prose Passages (F[2,23] = 7.04). After 6 weeks of supervised abstention from intoxicants, subjects in the cannabis-dependent group showed some significant improvement on the Wechsler Memory Prose Passages score and on the Benton Visual Retention Test; however, the improvement failed to achieve statistical significance. We concluded that cannabis-dependent adolescents have selective short-term memory deficits that continue for at least 6 weeks after the last use of marijuana.

Adolescent↗
PubMed1975

Memory functions six to nine months after electroconvulsive therapy.

Memory functions after electroconvulsive therapy (ECT) were assessed in 38 former patients who had received bilateral treatment, right unilateral treatment, or hospitalization without ECT six to nine months previously. Results of six different tests of delayed retention and remote memory provided no evidence for persisting memory impairment. Nevertheless, persons who had received bilateral ECT rated their memory as impaired significantly (P less than .05) more often than did persons in the other follow-up groups. Although considerable effort was made to maximize the sensitivity of the memory tests, it is possible that, long after ECT, some impairment of memory remained that was not detected by these tests. Alternatively, it is hypothesized that the impairment of recent and remote memory initially associated with bilateral ECT could cause some persons to become more alert to subsequent memory failures and then to underestimate their memory abilities.

Adult↗