Steven S. Matsuyama

Philothermal response of polymorphonuclear leukocytes in dementia of the Alzheimer type.

The philothermal response, i.e., the tendency of polymorphonuclear leukocytes (PMNs) to migrate along a temperature gradient toward warmer temperatures, was evaluated in 11 patients with a clinical diagnosis of dementia of the Alzheimer type (DAT) and compared to 11 age and sex-matched mentally normal individuals. While the total number of migrating PMNs did not differ significantly between these two groups, there was a significant difference in the spatial distribution of the responding cell population. The numerical parameter, R, has been introduced to provide a quantitative measure of the distribution of populations characterized by differences in motile behavior. This R value was unusually high for 10 of the DAT patients but only one of the comparison individuals. No relation between R and duration of illness, age, or sex was detected. These preliminary findings, based on a small number of clinically diagnosed DAT patients, suggest that the philothermal response may represent a biological marker with diagnostic usefulness for at least one subgroup of DAT patients.

Cognitive performance in relatives of patients with probable Alzheimer disease : an age at onset effect ?

Cognitive performance of 32 siblings and children of patients with probable Alzheimer disease was assessed longitudinally over an interval averaging 4 years. Mean scores were within normal limits for age on all measures at both test times. However, relatives of patients with early-onset dementia (less than or equal to 67 years) were more likely to show a decline in performance from the first to second testing than relatives of patients with late-onset dementia. Additional follow-up will be needed to determine the reliability of performance trajectories and to assess whether mild cognitive changes are related to future dementia. However, findings suggest that it may be important to consider family history of dementia in studies of normal cognitive aging.

Mutations specifically blocking differentiation of macroconidia in Neurospora crassa

The asexual life cycle of Neurospora crassa is comprised of three stages, vegetative hyphae, aerial hyphae, and macroconidia. Under appropriate environmental conditions these stages occur in an orderly temporal sequence making possible detailed observations of developmental changes in both living and fixed material. Attention is focused on the origin of conidiophores, from aerial hyphae, and the subsequent differentiation of mature macroconidia. Mutations at four genetically independent loci block the process of conidiation at different developmental points. Analyses of these strains and of double mutant strains constructed by crosses among them indicate the order in which the mutants are phenotypically expressed. Three of the mutations have no evident effects on either vegetative or aerial hyphae and hence appear to be “phase-specific” for macroconidia; tion. New evidence is presented in strong support of the idea that the products of these genes are formed in the aerial hyphae and/or conidiophores.

Thyroid Disease in Patients With Dementia of the Alzheimer Type

The authors compared the frequencies of prior thyroid disease, thyroid medication use, and abnormal serum thyroxine levels in 61 patients with dementia of the Alzheimer type (DAT) with those of 38 control subjects. They found that the 33 women with DAT had a 24.2% frequency of prior thyroid disease, comparable with that found in a previous epidemiologic study. The 19 female controls, however, had a similar frequency, failing to support a previously reported association between DAT and thyroid disease. J Am Geriatr Soc 33:538, 1985

Cognitive changes in young-old adults: effect of family history of dementia

Cognitive performance of 40 first-degree relatives of patients with probable Alzheimer disease was compared to that of 24 matched controls without a family history of dementia. Across a test-retest interval ranging from 1 to 6 years, relatives more often showed evidence of cognitive decline, and in multivariate analyses of memory and intelligence measures, relatives of patients with early-onset dementia (< 67 years) showed greater decline than controls or relatives of patients with late-onset dementia. All changes observed to date are in the subclinical range, and further follow-up will be needed to determine the reliability of change trajectories. However, the findings suggest that family history of dementia may be worthy of monitoring in research on normal cognitive aging.

Thermotaxis, chemotaxis and age

It has been demonstrated that polymorphonuclear leukocytes migrate in vitro along a temperature gradient, i.e., that they exhibit positive thermotaxis. The effect varies monotonically with the temperature gradient, a fact which suggests that PMN thermotaxis may be important in nonspecific immune amplification. Thermotaxis and chemotaxis are synergistic: simultaneously applied codirectional chemotactic and thermotactic stimuli produce a motile response that is more than double the sum of the separate effects. Conversely, counter-directional stimuli produce inhibition. Chemotaxis correlates positively with age for cell donors less than 35 years old, but there is no significant correlation with age for the cell donors older than 61 years in this small pilot sample. Neither is there a significant correlation between chemotaxis and thermotaxis. Nonetheless, these preliminary data seem to open new avenues for the study of cell response to inflammation.

HLA-A2 as a possible marker for early-onset Alzheimer disease in men☆

We performed HLA typing on 36 patients with clinically diagnosed Alzheimer disease and 25 controls. Antigen A2 was present in all ten men (100%) with early-onset (less than 60 years) dementia, a frequency significantly higher than the 30% frequency found in the cognitively intact men of a comparable age (p = 0.009, corrected). This increased A2 frequency was also significantly greater than the frequencies for all other patient subgroups, including late-onset men (40%, p = 0.008), early-onset women (44%, p = 0.004), and late-onset women (42%, p = 0.028). Our findings, if repeated in future studies with larger samples, suggest that HLA-A2 positive men may comprise a subgroup with increased susceptibility to early-onset disease.

Subjective memory loss in age-associated memory impairment: Family history and neuropsychological correlates

Abstract Self-ratings of everyday memory function and performance on memory tests were examined in 61 first-degree relatives of patients with Alzheimers disease (AD) and 41 matched controls without a family history of dementia. Subjective memory ratings were significantly related to depression scores, despite the low levels of depressive symptoms in this healthy sample. Relatives of patients with early-onset dementia had higher levels of memory complaints compared to control participants, mediated in part by higher levels of depressive symptoms among these relatives. For the sample as a whole, there was little relationship between subjective memory ratings and performance on memory tests, but among early-onset AD relatives, subjective perceptions of memory decline were associated with poorer memory performance.

Self-Reports of Memory Problems in Relatives of Patients With Probable Alzheimer's Disease

This study examined the relationship between subjective memory complaints and performance on tests of memory by relatives of patients with probable Alzheimers disease (AD) and by older adults without a family history of dementia. Relatives of AD patients did not differ significantly from controls either in level of complaint or in performance on neuropsychological tests. However, among relatives of patients with early-onset AD, significant correlations were found between performance on memory tests and self-rated changes in everyday memory. These findings raise the possibility that relatives who have entered the age range in which their parents or siblings developed dementia symptoms are monitoring their memory performance more diligently than relatives of patients whose illness began at much later ages or persons who have no close relatives with AD.

Middle-aged children of Alzheimer parents, a pilot study: stable neurocognitive performance at 20-year follow-up.

The objective of this pilot study on a convenience sample of 25 offspring of Alzheimer patients (mean age 61.5 ± 8.8 years; range, 50-82) was the early detection of neurocognitive decline. This preliminary report appears to be the first one dealing with 20-year follow-up of neurocognitive data of Alzheimer’s disease (AD) children. Digit symbol (Wechsler Adult Intelligence Scale) was the only of 11 neurocognitive measures with a significant decline. And that decline between first and last testing (mean = 19.98 ± 0.30 years) was on raw scores, not scaled scores. Neither parents’ age at onset of AD nor autopsy confirmation or offspring APOE-e4 status influenced neurocognitive results. More robust data than currently available are needed to confirm the findings of this first pilot study and to determine both the trajectory of neurocognitive decline in AD and the risks of developing AD faced by children whose parent had the disease.