Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles.

In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease.

Neuropsychological and glucose metabolic profiles in asymmetric Parkinson's disease.

Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.

Visuospatial cognition in Huntington's disease.

The notion of specificity of visuospatial dysfunction in Huntington's disease (HD) was evaluated in a sample of afflicted patients as a function of symptom duration, age at onset, and overall dementia severity. Factor analytic procedures indicated that overall visuospatial processing capacity (factor 1) as well as the ability for spatial manipulation (factor 3) was markedly affected in HD patients. In contrast, consistency of spatial judgment (factor 2) appeared to remain relatively intact in these patients. Age at onset seemed to have no relationship with any of these variables, whereas dementia severity demonstrated a significant relationship with overall visuospatial processing capacity. Most importantly, duration of symptoms was significantly associated with the declining ability to mentally perform spatial manipulations. The observation of circumscribed visuospatial impairment in HD patients may have important consequences for the further understanding of the neurobehavioral consequences of this disorder.

Subgroups in Alzheimer's disease: fact or fiction?

Alzheimer's disease, which accounts for the majority of all dementing disorders, presents with a wide spectrum of demographic, neuropsychological, pathological and biochemical characteristics. It has become increasingly clear that Alzheimer's disease is indeed heterogeneous and lack of success in symptomatic treatment may be in part related to this. In an attempt to evaluate the utility of possible subgrouping schemas, we reviewed current criteria used to subclassify patients with Alzheimer's disease. Results suggest that although treatment attempts may have to take a more individualized approach, most current subgrouping concepts will probably have limited therapeutic utility.

Clonidine treatment of Alzheimer's disease.

A loss of cortical noradrenergic innervation may contribute to the intellectual deterioration in Alzheimer's disease. To test the hypothesis that noradrenergic replacement may confer symptomatic benefit, a double-blind, placebo-controlled therapeutic trial with clonidine hydrochloride (Catapres), a centrally active noradrenergic receptor agonist, was undertaken in eight patients with the clinical diagnosis of Alzheimer's disease. No statistically significant changes in cognitive function were found over a range of doses, including those that produced clinically observable side effects. These preliminary results indicate a need for alternative noradrenergic replacement strategies in Alzheimer's disease.