ABSTRACT
Rigidity, slowness, gait impairment, and other disorders of movement accompany Alzheimer's disease (AD) at various stages of the illness. The presence of these so-called extrapyramidal features have been reported to predict disease prognosis and pathologic localization. Unfortunately, failure to accurately characterize the movement disorder, particularly to distinguish parkinsonism from cortically based motor disturbances (that is, paratonia, apraxia), makes the results of many published studies difficult to interpret. There is an important need to precisely characterize movement disorders in studies of AD to clarify the clinical phenomenology and neurobiology of the condition and to accurately distinguish AD from other degenerative dementias, such as dementia with Lewy bodies.
Subject(s)
Alzheimer Disease/diagnosis , Basal Ganglia Diseases/diagnosis , Gait Disorders, Neurologic/diagnosis , Parkinsonian Disorders/diagnosis , Aged , Dementia/diagnosis , Diagnosis, Differential , Humans , Neurologic Examination , PrognosisABSTRACT
The authors assessed the accuracy of published clinical criteria and their own modifications of those criteria in diagnosing Lewy body disease (LBD). Clinical diagnoses were made by two clinicians, blinded to neuropathologic diagnoses, using the Rochester Alzheimer's Disease Center database and traditional medical records. Neuropathologic diagnoses were made according to published guidelines. Results from 21 Alzheimer's disease and 18 LBD patients indicated that no set of clinical criteria was accurate in diagnosing LBD. The only significant predictor of LBD in this population was depression, which was more common in LBD than in Alzheimer's disease. The authors conclude that clinical identification of LBD is an important but unresolved neurological problem.
Subject(s)
Parkinson Disease/diagnosis , Adult , Aged , Alzheimer Disease/pathology , Brain/pathology , Databases, Factual , Female , Humans , Male , Middle Aged , Parkinson Disease/pathology , Parkinson Disease/psychologyABSTRACT
Dementia associated with cortical Lewy bodies on neuropathologic examination may comprise the second largest category of age-related cognitive impairment, after Alzheimer's disease. Despite its prevalence, a consensus has not yet been reached regarding the terminology, neuropathologic criteria, or clinical symptomatology of this postulated nosologic entity. Lewy body disease (LBD) is beginning to be diagnosed clinically in neuropsychiatric clinics, but universally accepted diagnostic criteria for LBD remain to be validated. In this article the authors review the literature on LBD, including both neuropathologic and clinical findings.
Subject(s)
Cerebral Cortex , Dementia/diagnosis , Parkinson Disease/diagnosis , Aged , Aged, 80 and over , Cerebral Cortex/pathology , Dementia/pathology , Female , Humans , Lewy Bodies/pathology , Male , Middle Aged , Neurologic Examination , Neuropsychological Tests , Parkinson Disease/pathologyABSTRACT
Eyeblink classical conditioning (EBCC) is severely and consistently impaired in probable Alzheimer's disease (AD), presumably due to normal age related changes in the cerebellum and AD-related hippocampal cholinergic disruption. Less consistent impairment and more variable EBCC performance was predicted in patients with cerebrovascular dementia (CVD) because some CVD patients should have impairment in EBCC when their lesions affect the EBCC circuitry, whereas others with lesions in noncritical regions should have normal EBCC. As predicted, variability in EBCC performance was greater in patients with CVD than in probable AD patients. Acquisition of conditioned responses in the group of CVD patients was better than in the probable AD group. These data show in another sample of normal control subjects and probable AD patients that EBCC has a high sensitivity for probable AD.
Subject(s)
Alzheimer Disease/physiopathology , Cerebrovascular Disorders/physiopathology , Conditioning, Psychological/physiology , Dementia, Vascular/physiopathology , Eye Movements/physiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
On the basis of what is known about the neural circuitry essential or normally involved in eyeblink classical conditioning (EBCC), the pattern of neurodegeneration in Huntington's disease (HD) would not appear to interfere with this type of learning. HD causes severe atrophy of the basal ganglia and thinning and shrinkage of the cerebral cortex. However, the hippocampus and hippocampal cholinergic system remain relatively intact, as does the cerebellum. Because the brain circuitry engaged in EBCC is neither lesioned nor disrupted in HD, it was predicted that HD patients would perform like normal control subjects in the 400-ms delay EBCC paradigm. Performance of seven patients with HD was compared to age-matched normals, with two control subjects matched to each HD patient. There were no differences in production of conditioned responses (CRs) between HD patients and normal control subjects, but the timing of the CR was abnormal in HD. Comparisons of HD patients to patients with other neurodegenerative diseases (probable Alzheimer's disease (pAD) and Down syndrome (DS) over the age of 35 with presumed Alzheimer-like neuropathology) and to patients with cerebellar lesions demonstrated significantly better EBCC performance in HD. Results suggest that the ability to acquire CRs is normal in HD, but the striatum may have some role in optimizing the timing of the CR.
Subject(s)
Conditioning, Classical/physiology , Conditioning, Eyelid/physiology , Huntington Disease/physiopathology , Mental Recall/physiology , Reaction Time/physiology , Adult , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Brain/physiopathology , Brain Mapping , Dominance, Cerebral/physiology , Female , Humans , Huntington Disease/diagnosis , Huntington Disease/psychology , Male , Middle Aged , Nerve Net/physiopathologyABSTRACT
Eyeblink classical conditioning (EBCC) is a useful paradigm for studying the neurobiology of learning and memory. EBCC shows large age effects and has been shown to be sensitive to Alzheimer-like neuropathology. The EBCC data of 241 participants, including young, middle-aged, and elderly normal adults, adults with Down's syndrome, and patients with probable Alzheimer's disease, were analyzed to identify a minimum number of trials for reliable assessment. Results indicate that EBCC performance can be as reliably assessed in 63 trials as in 90 trials. Using fewer conditioning trials reduces administration time, making EBCC more practical for both research and potential diagnostic purposes.
Subject(s)
Blinking , Conditioning, Classical , Adult , Age Factors , Aged , Down Syndrome , Humans , Middle AgedABSTRACT
Patients with probable Alzheimer's disease (AD) and hippocampal disruption are severely impaired in eyeblink classical conditioning (EBCC) in the 400 ms delay paradigm. Hippocampectomized rabbits are not impaired in the delay paradigm but perform poorly in the trace paradigm. It was anticipated that probable AD patients would be severely impaired in the 750 ms trace paradigm. In Study 1, probable AD patients were significantly impaired in the trace EBCC paradigm, but the sensitivity of the test was poorer than for the delay paradigm. In Study 2, probable AD patients tested in trace were tested in the delay paradigm 4 months later. Sensitivity for AD was also better for the delay paradigm. Rabbits and humans show behavioral parallels in the 400 ms delay paradigm but not in the 750 ms trace paradigm. The 400 ms delay EBCC paradigm was superior to the 750 ms trace paradigm for the detection of AD.
Subject(s)
Alzheimer Disease/physiopathology , Conditioning, Psychological/physiology , Eye Movements/physiology , Memory/physiology , Aged , Aged, 80 and over , Humans , Middle Aged , Reaction Time/physiologyABSTRACT
The cholinergic antagonist scopolamine delays acquisition of eyeblink classical conditioning (EBCC) in rabbits and humans, but scopolamine-treated organisms eventually acquire conditioned responses (CRs). Patients with probable Alzheimer's disease (AD) and older adults with Down's syndrome (DS/AD) have disrupted cholinergic systems and perform EBCC very poorly. It was hypothesized that patients with probable AD and DS/AD, like scopolamine-injected organisms, would acquire CRs if given sufficient training. Twelve probable AD patients, 12 DS/AD patients, and 6 healthy elderly control individuals participated in 5 daily 90-trial sessions of EBCC. Fifty-eight percent of the probable AD, 92% of the DS/AD, and 100% of the control participants achieved learning criterion. Probable AD, DS/AD, and control participants had statistically significant increases in the percentage of CRs produced over 5 EBCC sessions. The neural substrate for EBCC was not eliminated in probable AD or DS/AD patients, although the learning mechanism was disrupted.
Subject(s)
Alzheimer Disease/psychology , Blinking , Conditioning, Classical , Conditioning, Eyelid , Down Syndrome/psychology , Adult , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/physiopathology , Blinking/physiology , Cholinergic Fibers/physiology , Conditioning, Classical/physiology , Conditioning, Eyelid/physiology , Down Syndrome/diagnosis , Down Syndrome/physiopathology , Female , Humans , Male , Middle Aged , Reference Values , Retention, Psychology/physiologyABSTRACT
Individuals with either fragile-X syndrome or Down's syndrome with IQ scores less than 40 were assessed on the Down Syndrome Mental Status Exam. The results of the testing were examined for syndrome-specific cognitive profiles. No evidence for syndrome-specific cognitive profiles were found. These same individuals were then classified as high or low IQ, and each group was examined for IQ-level-specific profiles. Unique IQ level cognitive profiles were found. Classifying the individuals with regard to aetiology obscured IQ-level-specific strengths and weaknesses. Researchers and developers of curricula are cautioned against generalizing cognitive profiles to all IQ levels of a specific genetic syndrome.
Subject(s)
Down Syndrome/genetics , Fragile X Syndrome/genetics , Intelligence/genetics , Activities of Daily Living/classification , Activities of Daily Living/psychology , Adolescent , Adult , Disability Evaluation , Down Syndrome/diagnosis , Down Syndrome/psychology , Education of Intellectually Disabled , Fragile X Syndrome/diagnosis , Fragile X Syndrome/psychology , Humans , Male , Middle AgedABSTRACT
A total of 140 normal adults participated in one of seven conditions designed to test the hypothesis that memory systems may be distinguished on the basis of their neurobiological substrates. The results revealed a selective disruption of eyeblink classical conditioning (EBCC) when it was performed concurrently with tapping, another cerebellar task. Subjects simultaneously engaged in EBCC and a recognition task or control tasks were relatively unimpaired in EBCC. Results provide evidence for the existence of neurobiologically distinct memory systems, and suggest that the selective disruption of EBCC, when concurrently performed with tapping, may be attributed to cerebellar involvement in both tasks.
