Guerry M. Peavy

Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD

Background: Frontotemporal dementia (FTD) is currently distinguished from AD primarily on the basis of behavioral features because studies of cognition have shown negligible or inconsistent differences. However, the poor discriminability of cognitive measures may relate to reliance on imprecise clinically diagnosed groups. Therefore, a retrospective examination of neuropsychological test performance in autopsy-confirmed patients is warranted. Objective: To compare the pattern of cognitive deficits exhibited by patients with autopsy-confirmed FTD and AD. Methods: The profiles of cognitive deficits exhibited by patients with neuropathologic diagnosis of FTD (n = 14) or AD (n = 28) were compared. The Mattis Dementia Rating Scale (MDRS), letter and category fluency tests, Wechsler Intelligence Scale for Children–Revised block design test, Boston naming test, and clock drawing test were administered. Results: Multivariate analysis of covariance controlling for age, education, and level of dementia revealed that patients with FTD performed significantly worse than patients with AD on letter and category fluency tests but significantly better on the MDRS memory subscale, block design test, and clock drawing test. A logistic regression model, validated in an independent clinical sample, used letter fluency, MDRS memory, and block design scores to correctly classify 91% of AD patients and 77% of FTD patients. Conclusions: A double dissociation in the pattern of cognitive deficits exhibited by FTD and AD patients was demonstrated. The FTD patients were more impaired than AD patients on word generation tasks (i.e., verbal fluency) that are sensitive to frontal lobe dysfunction but less impaired on tests of memory and visuospatial abilities sensitive to dysfunction of medial temporal and parietal association cortices.

Behavioural abnormalities contribute to functional decline in Huntington’s disease

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington’s disease are examined. Twenty two patients with Huntington’s disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington’s disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease

Objective: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. Methods: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. Results: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. Conclusions: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Verbal memory performance of patients with human immunodeficiency virus infection: Evidence of subcortical dysfunction

In the present study, the California Verbal Learning Test (CVLT) was administered to symptomatic HIV+ (n = 31), asymptomatic HIV+ (n = 94), and HIV-normal control (HIV-NC) (n = 40) subjects to assess the prevalence and nature of their verbal memory deficits. Symptomatic HIV+ subjects were significantly impaired relative to HIV-control subjects on CVLT measures of acquisition and retention, and were significantly less likely than control subjects to use a semantic clustering strategy to support recall. The performance of the asymptomatic HIV+ subjects fell between those of the symptomatic HIV+ subjects and HIV-controls on almost every CVLT measure. A linear discriminant function analysis (DFA) was used to compare the performances of these three groups to Alzheimers disease (AD). Huntingtons disease (HD), and normal control (NC) subjects on three CVLT measures, including total recall over five learning trials, intrusion errors, and a derived score of delayed recognition discriminability minus the final learning trial. Significant differences were found between the number of symptomatic HIV+ subjects classified as HD (32%), AD (3%), and normal (65%), the number of asymptomatic HIV+ subjects classified as HD (16%), AD (1%), and normal (83%), and the number of HIV-NC subjects classified as HD (2%), AD (0%), and normal (98%). The profile of verbal memory deficits exhibited by the subgroup of impaired HIV+ subjects was similar to that of patients with HD, a prototypical subcortical dementia, and different from that of patients with AD, a prototypical cortical dementia. This finding is consistent with reports of the predominance of subcortical neuropathological changes associated with HIV infection.

Effects of Chronic Stress on Memory Decline in Cognitively Normal and Mildly Impaired Older Adults

OBJECTIVE The literature provides evidence of a strong relationship between greater stress and memory loss, but few studies have examined this relationship with both variables measured over time. The authors sought to determine the prospective association between subjective and objective measures of chronic stress and rate of memory decline in cognitively normal and mildly impaired older adults. METHOD This longitudinal study was conducted at a university research center and included 61 cognitively normal subjects and 41 subjects with mild cognitive impairment (ages 65-97). Fifty-two subjects were followed for up to 3 years (mean=2 years) and received repeated stress and cognitive assessments. Exclusion criteria were dementia, significant medical or psychiatric conditions, and medication use (e.g., corticosteroids) that might affect cortisol level or cognitive functioning. The main outcome measure was a regression-based slope reflecting performance change on tests of global cognition and episodic memory as a function of baseline diagnosis, recent life events, and salivary cortisol. Examiners were blind to stress ratings and cortisol levels at the time of cognitive testing. RESULTS Higher event-based stress ratings collected over the follow-up period were associated with faster cognitive decline in subjects with mild cognitive impairment but not in cognitively normal subjects. In contrast, higher cortisol levels were associated with slower cognitive decline in subjects with mild cognitive impairment but not in cognitively normal subjects. CONCLUSIONS Chronic stress affects cognitive functioning differently in cognitively normal subjects and those with mild cognitive impairment. Cortisol, while likely to have neurotoxic effects over time, may enhance cognitive functioning in older adults compromised by existing cognitive deficits.

The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults

BACKGROUND Chronic elevations in cortisol associated with prolonged stress have been associated with memory loss, as has the apolipoprotein E gene (APOE-epsilon4) genotype. Combined effects of stress and APOE status on memory and cortisol in humans have not been studied. METHODS A semistructured interview with standardized scoring was used to measure stress level and univariate analysis of variance to assess effects of stress and APOE-epsilon4 status on memory and salivary cortisol in 91 nondemented subjects (mean age 78.8 years). RESULTS Low-stress subjects performed better than high-stress subjects on delayed recall of stories (p = .04), word lists (p = .02), and visual designs (p = .04). APOE-epsilon4-negative subjects obtained better scores than epsilon4-positive subjects on immediate (p = < .01) and delayed (p < .01) recall of visual designs. Significant stress by APOE-epsilon4 interaction effects on memory (p = .03) and cortisol (p < .01) resulted from consistently worse memory and higher cortisol concentrations in the high stress, epsilon4-positive group. CONCLUSIONS These findings are consistent with a model in which prolonged exposure of older, nondemented individuals to stress in the presence of an epsilon4 allele leads to memory decline. Further studies will assess whether stress and APOE-epsilon4 interact to increase the risk of developing Alzheimers disease.

Rate and correlates of weight change in Huntington’s disease

Objective: To determine the rate and correlates of weight change in a large, well characterised sample of patients with Huntington’s disease followed at 44 sites by the Huntington Study Group. Participants and methods: Weight change was assessed in 927 adults with a definite diagnosis of Huntington’s disease who were followed prospectively for (mean (SD)) 3.4 (1.4) years. The unified Huntington’s disease rating scale was used to assess weight, motor dysfunction (including chorea and dystonia), depressive symptoms, and functional decline. Results: Random effects modelling determined that patients gained an average of 0.11 (1.7) kg/year and their chorea scores increased by 0.36 (0.78) points/year. There were significant but weak relations between weight loss and increasingly severe chorea (r  =  −0.13), worse baseline motor performance (r  =  −0.12), less severe baseline depressed mood (r  =  0.14), and poorer baseline independence ratings (r  =  0.07). Patients who were within 0 to 2 years of symptom onset at the time of the baseline visit gained more weight than those with longer disease duration. Conclusions: Weight loss following symptom onset is not a consistent feature of Huntington’s disease. The mechanisms contributing to weight change in this condition are unclear and probably multifactorial. Future studies examining asymptomatic carriers of the mutation could be helpful in identifying incipience of low body weight and may be better suited for identifying clinical correlates of weight loss than studies in symptomatic patients.

Frontal behavioral syndromes and functional status in probable Alzheimer disease.

OBJECTIVE / METHOD The authors used the Frontal Systems Behavior Scale (FrSBe) to determine the frequency of frontal behavioral syndromes in 49 subjects with mild-to-moderate dementia and 23 subjects with severe dementia of Alzheimer disease (AD) and 23 healthy control (HC) participants. RESULTS / CONCLUSIONS Frontal behavior syndromes occurred with higher frequency in AD. Apathy and executive dysfunction were elevated both in mild-to-moderate and severe AD. Disinhibition was elevated only in severe AD. In AD, apathy was associated with difficulty in basic activities of daily living (ADL), whereas executive dysfunction was related to impairment in instrumental ADLs.

Cognitive and Functional Decline in Huntington's Disease: Dementia Criteria Revisited

The importance of designating criteria for diagnosing dementia lies in its implications for clinical treatment, research, caregiving, and decision‐making. Dementia diagnosis in Huntingtons disease (HD) is often based on criteria developed for Alzheimers disease requiring memory loss. However, it is likely that other cognitive deficits contribute to functional impairment in HD before memory declines. The goal is to identify cognitive deficits that contribute to functional impairment to support dementia criteria that reflect HD neuropathology. Eighty‐four HD mutation‐positive subjects completed neuropsychological tests and the Unified Huntingtons Disease Rating Scale Functional Independence Scale (FIS). Functional impairment was defined as 80 or below on the FIS. Speed of processing, initiation, and attention measures accounted for 70.0% of the variance in FIS ratings (linear regression) and correctly classified 91.7% of subjects as functionally impaired or intact (logistic regression). Measures of memory, motor impairment except dysarthria, neuroleptic use, and depressed mood did not improve prediction. A definition of HD dementia that includes cognitive impairment in at least two areas of cognition but does not require a memory deficit, in the context of impaired functional abilities and a deteriorating course, more accurately reflects HD neuropathology and could lead to improved research methods and patient care.

Memory for verbal information in individuals with HIV-associated dementia complex

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, & Price, 1986).