Patterns of brain atrophy in frontotemporal dementia and semantic dementia.

OBJECTIVE: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD). METHODS: Twenty patients with FTLD were classified as having FTD (N = 8) or SemD (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry. RESULTS: Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, group showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally. CONCLUSIONS: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD may underlie some the behavioral symptoms seen in the two disorders.

Evidence that age-associated memory impairment is not a normal variant of aging.

The concept of age-associated memory impairment (AAMI) suggests that clinically recognized memory dysfunction can be a feature of normal aging. To determine whether AAMI represents a variant of normal aging, we longitudinally studied individuals meeting AAMI criteria for development of dementia. Two hundred two community-living individuals (mean age, 77 years) with or without mild memory impairment were assessed annually for an average of 3 years at the Washington University Alzheimer's Disease Research Center. At baseline, no individual was unequivocally demented, as defined by a Clinical Dementia Rating (CDR) score of 1 or greater. Modified National Institute of Mental Health criteria were used to identify individuals with AAMI who otherwise met a criterion for cognitive normality. The Short Blessed Test (SBT) was used as a measure of general cognitive function; conservative (SBT = 5) and permissive (SBT = 10) cutoff scores were used as indicators of cognitive normality. With the more permissive measure of cognitive normality, 59 (29%) of the 202 individuals met AAMI criteria. Progression to dementia by 3 years occurred in 42% of AAMI individuals versus 16% of the individuals who did not meet AAMI criteria. With the more restrictive SBT cutoff of 5, 22% of individuals met AAMI criteria; progression to dementia occurred in 31% of these individuals versus 9% of the individuals without AAMI. Survival times to dementia differed significantly between AAMI and non-AAMI groups defined by either cutoff score. Our findings indicate that individuals with AAMI have a three-fold greater risk for development of dementia than individuals who do not meet AAMI criteria. Hence, AAMI may represent a dementia prodrome rather than a benign variant of aging.

Cognitive and neurobehavioral functioning after mild versus moderate traumatic brain injury in older adults.

This study evaluated the early cognitive and neurobehavioral outcomes of older adults with mild versus moderate traumatic brain injury (TBI). Thirty-five patients who were age 50 years and older and sustained mild or moderate TBI were prospectively recruited from acute care hospitals. Patients were administered cognitive and neurobehavioral measures up to 2 months post-injury. Demographically comparable control participants received the same measures. Patients and controls did not have previous histories of substance abuse, neuropsychiatric disturbance, dementia, or neurologic illness. Moderate TBI patients performed significantly poorer than mild TBI patients and controls on most cognitive measures, whereas the mild patients performed comparably to controls. In contrast, both mild and moderate patients exhibited significantly greater depression and anxiety/somatic concern than controls. The results indicate that the classification of TBI as mild versus moderate is prognostically meaningful as applied to older adults. The findings extend previous investigations in young adults by demonstrating a relatively good cognitive outcome on objective measures, but subjective complaints after a single, uncomplicated mild TBI in older persons.

Absence of cognitive impairment or decline in preclinical Alzheimer's disease.

OBJECTIVE: To determine whether clinically nondemented elderly individuals with pathologically confirmed preclinical AD are characterized by cognitive decline as measured by psychometric tests before death. METHODS: Psychometric performance was examined retrospectively in 14 individuals who were nondemented at time of death and grouped in accordance with their neuropathologic findings: 1) Healthy brain (n = 9) was characterized by the absence of senile plaques or by only patchy neocortical deposits of plaques; 2) preclinical AD (n = 5) was characterized by neuritic and diffuse plaques distributed throughout the neocortex. All individuals showed neurofibrillary pathologic change in medial temporal lobe structures. For comparison, we also evaluated 10 individuals who died in the earliest symptomatic stage of dementia of the Alzheimer type (DAT). All individuals had been assessed by clinical and psychometric measures during life. The psychometric measures yielded a standardized factor score that represented global cognitive performance. RESULTS: At the last assessment before death, individuals with very mild DAT were impaired on the factor score and on individual psychometric measures with respect to the nondemented individuals. Those nondemented individuals with preclinical AD did not differ in performance from those with healthy brains. For individuals with at least three psychometric assessments during life, there was no decline in performance for either those with healthy brains (n = 5) or preclinical AD (n = 3), although decline was evident for very mild DAT individuals (n = 5). CONCLUSIONS: Pathologically confirmed preclinical AD is not associated with cognitive impairment or decline, even on measures shown to be sensitive to very mild DAT.

Motor dysfunction in mildly demented AD individuals without extrapyramidal signs.

BACKGROUND: Although not as prominent as cognitive decline, motor dysfunction occurs in AD, particularly in the later stages of the disease. OBJECTIVE: To determine whether early-stage AD is also characterized by motor impairment. METHODS: We examined very mildly (Clinical Dementia Rating [CDR] 0.5) and mildly (CDR 1) demented AD individuals in comparison with healthy elderly control individuals (CDR 0) on a variety of nonmotor cognitive and psychomotor measures and on four motor measures (gait velocity, finger tapping, reaction time, movement time). To minimize the possibility of extrapyramidal dysfunction contaminating the groups, only individuals who were clinically free of extrapyramidal signs were included in the study. RESULTS: Mildly demented AD individuals were slowed on all motor measures except for finger tapping. No evidence of motor dysfunction was found in the very mildly demented AD group. As expected, both AD groups were impaired on the nonmotor cognitive and psychomotor tests. CONCLUSIONS: These results indicate that AD alone, in the absence of clinically confirmed extrapyramidal dysfunction, is associated with motor slowing in a stage-dependent manner. It remains to be determined whether this motor slowing represents a general characteristic of mild AD or indicates other neuropathology such as PD or the Lewy body variant of AD.

The mere exposure effect in patients with Alzheimer's disease.

The mere exposure effect was examined in patients with mild to moderate Alzheimer's disease (AD). Twenty patients and 20 elderly controls judged the physical characteristics of faces. Implicit memory was tested later by presenting pairs of faces (old and new) and asking participants which faces they liked better. Patients and controls exhibited above chance preference for previously exposed faces. Experiment 2 evaluated whether the preserved implicit memory of patients was mediated by explicit memory. Patients and controls again judged faces but then later chose which faces they had seen before. Patients exhibited impaired recognition memory compared to controls. These findings suggest that a mere exposure effect for unfamiliar faces is present in mild to moderate AD. The results are discussed in terms of perceptual and conceptual priming and relatively spared occipital lobe functioning in early AD.

Cognitive and behavioral sequelae of closed head injury in older adults according to their significant others.

This study examined the neurobehavioral effects of closed head injury (CHI) in older adults according to their significant others. Informants of 17 mild and moderate CHI patients > or = 50 years old when injured completed the Geriatric Evaluation of Relative's Rating Instrument, a questionnaire inquiring about the patient's cognition, affect, interpersonal relations, and daily activities. The significant others provided retrospective ratings of preinjury functioning and completed the same instrument an average of 4 and 13 months post-injury. The significant others of 10 community-residing, normal control subjects completed the questionnaire at comparable intervals between each rating. Compared with their preinjury functioning, and unlike the control subjects, patients showed declines in cognition and mood. The possible impact of these changes, including their effect on subjective burden in caregivers, is discussed.

Cognitive and motor functioning in Parkinson disease: subjects with and without questionable dementia.

BACKGROUND: The nature of cognitive performance in subjects with Parkinson disease (PD) without dementia is controversial, perhaps because of failure to exclude subjects with unrecognized very mild dementia. OBJECTIVE: To compare cognitive and motor functioning in well-characterized subjects with PD without overt dementia with healthy elderly control subjects. DESIGN: Subjects' conditions were evaluated clinically and psychometrically at entry into a longitudinal study of cognitive and motor performance in elderly subjects. Measures included a global dementia staging scale, the Washington University Clinical Dementia Rating; psychometric tests, including Logical Memory, Digit Span, Associate Learning, Information, Block Design, Digit Symbol, Trail-making A, Crossing-off, Boston Naming Test, and Word Fluency; and motor measures, including finger tapping, gait velocity, reaction time, and movement time. SETTING: A university-based research facility. SUBJECTS: There were 3 groups of subjects: healthy elderly control subjects (n=43), subjects with PD without dementia (n=58), and subjects with PD with questionable dementia (n=22), each evaluated at time of entry. RESULTS: As expected, both PD groups were impaired on motor measures (gait velocity, finger tapping, and movement time) compared with the healthy elderly control group. Neither PD group showed slowing in reaction time. The subjects with PD with questionable dementia were more impaired on Logical Memory, Block Design, Digit Symbol, and Trailmaking A compared with the subjects with PD without dementia. Although free of clinically evident cognitive dysfunction (Clinical Dementia Rating score, 0), the PD group without dementia was impaired with respect to the healthy elderly control group on all measures from the psychometric assessment except Digit Span, Associate Learning, and Word Fluency. CONCLUSIONS: The PD group without dementia showed global cognitive impairments in comparison with the healthy elderly control group, possibly because the healthy elderly control subjects represented idealized aging. Although the deficits were of small magnitude, this finding suggests that PD may predispose to subclinical cognitive impairment. Longitudinal follow-up is required to determine whether subjects with PD destined to develop overt dementia can be distinguished from those who do not.

Cognitive speed in nondemented Parkinson's disease.

Studies of speed of cognitive processing in Parkinson's disease (PD) have yielded mixed results. This may relate in part to a differential effect on cognitive speed by the type of information to be processed. In the present study, we compared medication fasted, nondemented individuals with mild idiopathic PD (N = 26) with age-matched controls (N = 12) on a test requiring easy and hard same-different discriminations for verbal, quantitative, and spatial information, as well as on a traditional memory scanning paradigm. A voice-activated relay rather than a key press was used to eliminate the need for limb and finger movements. Simple reaction time and movement time were also measured in a task requiring subjects to move a hand held stylus to a designated target. The PD group performed as fast as the control group across all tasks except movement time. Thus, in our paradigm, the presence of PD alone does not predict cognitive slowing in the presence of motor slowing.

Source memory in mild to moderate Alzheimer's disease.

This research examined whether source memory is preserved in patients with mild to moderate Alzheimer's disease (AD). In Experiment 1, AD patients and normal elderly controls recalled true facts (information acquired outside of the experimental setting) and made-up facts (information acquired in the experiment), and they determined the source of these memories. Relative to controls, AD patients recalled fewer facts, but when they remembered this information, they attributed their learning to the correct source. In Experiment 2, memory of made-up facts was equated between groups by incorporating a 1-week recall delay for the controls. Again, AD patients accurately determined whether facts were learned inside or outside of the experiment. However, both groups performed at chance in terms of their memory for whether a made-up fact was read on a card or told by the examiner. The findings indicate relative preservation of source memory in the earliest stages of AD and are discussed in terms of methodological problems in testing source memory in impaired groups and in terms of frontal-lobe functioning.

Indirect memory during anesthesia. The effect of midazolam.

BACKGROUND: The preservation of implicit memory function during anesthesia is controversial, with conflicting results appearing in the literature. This study was designed to elucidate the effect of midazolam as part of an anesthetic technique on implicit memory function during anesthesia. Using a prospective randomized, double-blind study design, performance in three tasks (category generation, free association, and homophone spelling) was assessed. METHODS: Forty-eight consenting patients were assigned to two equal groups, to receive 2 mg intravenous midazolam or normal saline before induction of anesthesia. Anesthesia was induced with fentanyl and propofol and maintained with isoflurane 1.3 MAC until incision and isoflurane 1.0 MAC in 70% nitrous oxide thereafter. Fentanyl was used for supplementation of anesthesia. During anesthesia, one of two 50-min tapes containing the test material was played to each patient on a portable cassette player. In the postanesthesia care unit and 48 h after surgery, patients were engaged in three tasks by an observer unaware of the treatment group or tape. RESULTS: No significant main effect of priming or midazolam was observed in any of the tasks. In the word-association task, an interaction was observed between priming and treatment group (F = 9.62, P < .01) due to negative priming in the placebo group. CONCLUSIONS: The lack of a main effect of priming in any of the three tasks is consistent with the conclusion that indirect memory was not demonstrated for events occurring during the standard anesthetic conditions of this study. Further, midazolam appeared to have no effect.

Very long-term memory for odors: retention of odor-name associations.

The ability to remember odor-name associations for recent odors (those associated with everyday products experienced within the past 2 years) and distant odors (those associated with children's toys not encountered for 3 years or more) was examined in two experiments. In recognition tasks, subjects attempted to match odor names to odors, or odors to odor names. In a recall task, subjects tried to identify odors by name. The results showed that although odor retention was better for recent than distant odors, significant retention remains for odors not experienced since childhood. These results are consistent with other studies that found very slow and gradual loss of odor information in memory. They extend that research by showing that odor information is still available over a much longer period of time.

Indirect assessment of memory for music during anesthesia.

STUDY OBJECTIVE: To obtain evidence for intraoperative registration of auditory information in patients undergoing elective surgery. DESIGN: Within-subject design with three levels of frequency of exposure to music. SETTING: A university hospital and a university language laboratory. PATIENTS: Thirty-four patients scheduled for elective surgery and 20 healthy undergraduate psychology students. INTERVENTIONS: Selections of instrumental ethnic music were played to patients for 0, 3, or 12 exposures in one experiment and for 0, 6, or 24 exposures in another study. The undergraduates heard 0, 3, or 12 exposures of the music while awake. MEASUREMENTS AND MAIN RESULTS: Forty-eight hours after hearing the music, all subjects were tested on their preference for the selections they had heard as well as selections they had not heard. For the patients, the mean preference ratings (in millimeters, mm) on a visual analog scale following 0, 3, and 12 exposures were 73.3 mm, 74.0 mm, and 65.1 mm, respectively, a nonsignificant difference. For the patients who were exposed to the music 0, 6, and 24 times, the mean preference ratings were 64.4 mm, 66.1 mm, and 70.6 mm, respectively, a nonsignificant difference. For the waking participants, the mean preference ratings following 0, 3, and 12 exposures were 55 mm, 66.2 mm, and 62.5 mm, respectively, a significant difference (p less than 0.05). CONCLUSIONS: The anesthetized patients did not exhibit indirect memory for music played intraoperatively, at least to the extent required to demonstrate an exposure effect.