F. Jacob Huff

Time Dependency of Cognitive Recovery with Cobalamin Replacement: Report or a Pilot Study

To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction.

Automatic and attentional mechanisms of semantic priming in alzheimer's disease

Previous studies using a word-naming task have suggested that in demented patients, semantic priming results only from automatic spreading activation and not from attention-dependent processes. If this is true, then on a lexical-decision task where attention-dependent processes are a major source of the semantic-priming effect, demented patients should show little or no priming. To test this prediction, three groups of 16 subjects (young and normal-old individuals and patients with Alzheimers disease) were given a Word-Naming and a Lexical-Decision task. In both tasks, the amount of semantic priming (the difference in response time to a word preceded by a semantically unassociated vs. a semantically associated word) was determined. Demented patients showed significantly greater semantic priming than either normal group on both tasks. This result argues against the hypothesis that the semantic priming found in demented patients is due solely to automatic processes.

Age at Onset and Rate of Progression of Alzheimer's Disease

Age at onset, duration, and severity of dementia were evaluated in 165 patients with a clinical diagnosis of Alzheimers disease. Rate of progression of dementia was determined in 77 patients by repeated administration of the Blessed Dementia Scale (BDS). The distribution of age onset among patients was bimodal, with a division at about age 65. Duration of dementia at the time of initial examination was shorter, and rate of progression on follow‐up examination was more rapid in senile‐onset (age 65 or greater) than in presenile‐onset (before age 65) cases. Considerable overlap among values for the two patient groups was observed for both variables, indicating that age at onset is not a strong predictor of rate of progression of dementia in patients with Alzheimers disease.

Risk of dementia in relatives of patients with Alzheimer's disease

Using a family history questionnaire, we investigated the occurrence of dementia among relatives of patients with a clinical diagnosis of Alzheimers disease (AD) and among the relatives of age-matched control subjects. Cumulative lifetime risk of developing AD-type dementia was greater among relatives of AD probands and was consistent with an autosomal dominant genetic mode of transmission. Although the lifetime risk of AD-type dementia was similar among relatives of early-onset and late-onset AD probands, relatives of early-onset probands tended to have an earlier onset of dementia than did relatives of late-onset AD probands. This result raises the possibility that age at onset of dementia in AD may be genetically determined.

A comparison of lexical-semantic impairments in left hemisphere stroke and Alzheimer's disease.

Patients with aphasia due to left hemisphere stroke and patients with Alzheimers disease, who were matched for severity of naming impairment, were compared on tests of lexical-semantic processing. The results suggest that the lexical-semantic impairments in both groups are due to a combination of impaired access to, and loss of, lexical-semantic information, but that impaired access is more prominent in stroke patients, whereas Alzheimers disease patients suffer a greater loss of information. The results are discussed in terms of a brain model of the storage and processing of lexical-semantic information, and with respect to implications for treatment strategies.

Serial sevens versus world backwards: a comparison of the two measures of attention from the MMSE.

This paper reports on a comparison of the two alternative tests of attention in the Mini-Mental State Examination (MMSE), a well-known cognitive screening tool. The two tests, serial subtraction by seven and backwards spelling of the word world, are often used interchangeably. In a large population-based sample, the two tests were found to be weakly associated with each other, with the former test appearing more difficult, although both were strongly associated with educational level. The authors discuss the implications of this finding in clinical and research settings, and make recom mendations for more consistent use of the instrument. (J Geriatr Psychiatry Neurol 1990;3:203-207).

Factor structure of the mattis dementia rating scale among patients with probable alzheimer's disease

Abstract The Mattis Dementia Rating Scale (MDRS) is widely used to evaluate cognitive function in older adults who may be suffering from dementing illnesses. This report describes a factor analytic approach taken to investigate the constructs underlying the performance of patients with probable Alzheimers Disease. Three factors emerged from our analysis relating to: (a) conceptualization (b) construction and (c) memory. There was deviation between the original MDRS scheme and the clustering of the items in the factor analysis. A shortened test was developed from 11 of the original 17 items which loaded most heavily on the three factors.

Cognitive function and platelet membrane fluidity in Alzheimer's disease

Increased platelet membrane fluidity, as reflected by a decrease in the fluorescence anisotropy of diphenylhexatriene in labeled membranes, identifies a clinically distinct subgroup of approximately 50% of patients at our center who meet NINCDS-ADRDA clinical criteria for Alzheimers disease. In the current study, we compared the cognitive impairments of patients in this subgroup to those observed in the residual subgroup of patients with Alzheimers disease who had normal platelet membrane fluidity. No significant differences in the number or distribution of deficits in six cognitive domains were observed between the two subgroups. However, in the subgroup with increased platelet membrane fluidity, there were significantly more patients who exhibited dissociation of deficits on tests related to left and right parietal lobe function than in the residual subgroup. Moreover, the cases with dissociation of deficits consisted almost entirely of patients with deficits on tests reflecting left parietal lobe function and no deficit on tests of right parietal lobe function.

In Reply to Froda, Braekeleer, and Gauvreau

to 74 years (P = O.l), and none for the age-group 55 to 59 years (P = 0.24). Therefore, there is no statistical confirmation of the apparent bimodality reported in their study. In conclusion, it can be said that our data, as well as that reported by Huff et al, have a unimodal distribution. However, since a relatively small number of cases distributed over a large range of ages was analyzed, we cannot claim that these results are decisive. Nevertheless, we consider to be of interest to draw your attention to the distribution of the age at onset of our data, as well as to the use of the Haldane method when testing for bim~dality.~

Reply to Borrie, Crilly, and Bowring

To the Editor-We appreciate the comments of Borrie et al. on our study of age at onset and rate of progression of Alzheimer’s disease. Measuring the rate of progression of Alzheimer‘s disease is problematic, and there is presently no generally accepted method of measurement. We elected to measure progression by determining change over time in the total score (the sum of all subscales) on the Blessed Dementia Scale (BDS).2 We propose that this is a valid method because the BDS is sensitive to a range qf clinical manifestations of Alzheimer’s disease, and because it has been demonstrated to correlate with the severity of neuropathological abnormalities observed in postmortem examinations.2 Borrie et al. suggest that the activities of daily living component of the BDS may change due to physical illnesses during the follow-up period, resulting in a change in total BDS score that may exaggerate the actual change in severity of dementia. The implication of this suggestion is that such artefactual change in BDS scores may be more common in senile-onset than in presenile-onset cases, perhaps explaining our observation of more rapid progression in senile-onset cases. This is an important concern, and in fact the ratings for some items (eg, “Inability to perform household tasks”) on the “Changes in Performance of Everyday Activities” subscale of the BDS may be influenced by physical illnesses that do not affect mental status. The instructions for the BDS, however, specify that inquiries be “directed toward changes in capacity,” and that allowances be made in scoring “for physical disabilities that would restrict activities”.2 Moreover, the majority of items are directly concerned with changes in cognitive abilities (eg, “Inability to recall recent events”), for which confounding effects of physical illnesses do not pose a problem. In our study, we recorded two subscores: one (hereafter, subscale ”A”) comprising the sum of scores on the “Changes in Performance of Everyday Activities”, “Changes in Habits,” and “Changes in Personality, Interests, and Drive” subscales; the other (hereafter, subscale “B’) consisting of the “Information-Memory-Concentration Test” subscale. The mean scores at initial evaluation for the early-onset and late-onset patient subgroups were 6.9 and 6.4, respectively, for subscale A, and 17.7 and 17.6, respectively, for subscale B. Scores were not significantly different between groups by t-tests for either subscore of the BDS. For patients in whom follow-up testing was done, the rate of change (in score points per month) was greater in late-onset than in early-onset patients for subscale A (difference between groups 0.21 pointdmonth; p = .03 by t-test) and subscale B (0.14 pointdmonth), although the latter difference was not statistically significant. A repeated measures analysis of variance crossing subject group (early-onset versus late-onset) with BDS subscale (A versus B) revealed no interaction (p > .50), indicating that the difference in rate of progression between patient groups was similar whether measured by either subscale A or B. Although the difference between groups for subscale B was not statistically significant, the direction of the difference suggests more rapid deterioration in lateonset cases, which is the same conclusion that was drawn based on the total BDS score. We consider the failure to obtain statistical significance in examining subscale B to result from the decrease in statistical power that occurs in fractionating the BDS, rather than from a differential effect of other medical conditions in the two groups on subscales A and B. This interpretation is supported by the failure to find a group-by-subtest interaction using analysis of variance. A more direct approach to the question raised by Borrie et al. would be to examine presence of medical illnesses that might influence performance on ADL as covariates in analysis of change in BDS subscales. Such an analysis would be a useful refinement to our method of measuring progression of dementia. We don’t consider presence of such illnesses to be a substantial confounding factor in determining BDS scores, however, for the reasons presented above. We don’t, therefore, expect that such an analysis would alter our conclusions regarding age at onset and rate of progression of Alzheimer’s disease.