Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type

Abstract

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 midly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.

The cognitive neuroscience of ageing

“…Older adults with the ε4 allele who engaged in more physical activity had greater memory-related activation in posterior temporal and parietal regions than non ε4-carriers or those with lower physical activity. This result is particularly interesting as these areas are some of the first regions of cortex to show metabolic deficits in early AD [169][170][171] . This work shows interesting influences of both APOE genotype and physical activity on memory-related brain activation in cognitively intact but genetically at-risk older adults, but it is not clear if this increase is compensatory or protective against future cognitive decline.…”

A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease

“…This capability may be useful in characterizing patterns of deterioration in AD and thus may also provide further functional and anatomical clues to the heterogeneity of AD (cf. Martin et al, 1986;Grady et al, 1988). …”

Relational Integration and Executive Function in Alzheimer's Disease.

“…Prefrontal dysfunction may stem from a pathological process distinct from that responsible for the standard profile of AD, but it may also stem from the same pathological process (such as the death of cholinergic neurons). As Grady et al (1988) noted, sequential involvement of cortical areas in the disease process could also be explained by progressive degeneration of acetylcholine-producing cells in the nucleus basalis of Meynert (nbM) because different cortical lobes are innervated by different sections of nbM (Grady et al, 1988). Degeneration of acetylcholine-producing cells in the nbM is one factor that has been frequently implicated in the cognitive deficits observed in AD (Whitehouse, Price, Clark, Coyle, & DeLong, 1981).…”