Relationship between hyperglycemia and cognitive function in older NIDDM patients.

The nature and extent of cognitive impairment was examined in 29 healthy elderly subjects (mean age 69.8 yr) with non-insulin-dependent diabetes mellitus (NIDDM) and 30 demographically similar nondiabetic community volunteers (mean age 68 yr). Measures of verbal learning, abstract reasoning, and complex psychomotor functioning were performed more poorly by diabetic than nondiabetic subjects. Conversely, there were no between-group differences in performance on tasks involving pure motor speed and simple verbal abilities. Within the diabetic group, individuals with poorer metabolic control performed more poorly on tasks involving learning, reasoning, and complex psychomotor performance, although this relationship was not evident for simple verbal or motor tasks. These data indicate that older people with NIDDM who are functioning well and perceive themselves as in good health are likely to manifest greater deficits than healthy elderly people in processing complex verbal or nonverbal material. Possible explanatory mechanisms are discussed, and directions for future research are explored.

Visual event-related potentials and depression in the elderly.

Event-related potentials (ERPs) were recorded during a visual discrimination task from nine elderly individuals (mean=68.1 years), diagnosed as having major depressive disorder, and nine age-matched controls (mean=68.0 years). During the task, subjects pressed a switch to targets (the number 9) and ignored background (the number 6) and novel stimuli (random designs). Novel and target stimuli were both interspersed infrequently in the sequence of background stimuli. Scalp electrical activity was recorded from midline frontal (Fz), central (Cz), and parietal (Pz) sites. Depressives were characterized by lengthened response times and increased number of errors across the session. Speed of response was also found to vary directly with clinical status. Additionally, ERP correlates of depression in the elderly were found: N1 was more prolonged for target than non-target stimuli in the depressed group; P2 was larger for all conditions; N2 was uniformly small across the scalp, whereas the controls showed small N2 amplitudes only at Fz; large P3s appeared in trials following the novel stimuli in the depressed but not in the control group. These results are interpreted in terms of the symptomatology associated with depression (i.e., distractability, impaired short-term memory or concentration, indecisiveness) and possible age-related changes in the ERP scalp distribution.

No association between the alpha 1-antichymotrypsin A allele and Alzheimer's disease.

The alpha 1-antichymotrypsin (ACT) A allele was recently associated with Alzheimer's disease (AD), and the ACT AA genotype was reported to be more frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and in 102 elderly control subjects. ACT A allele frequencies were similar in AD subjects (0.503) and elderly controls (0.519). In addition, we found no evidence that in AD the AA genotype is more frequent in subjects with the APOE epsilon4 allele than in those without it. Our results do not support an association between the ACT A allele and AD.

Alpha2 macroglobulin and the risk of Alzheimer's disease.

BACKGROUND: alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56). METHODS: We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism. RESULTS: We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors. CONCLUSIONS: Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.

Cognitive-behavioral therapy and treatment for late-life depression.

Cognitive-behavioral therapy is a brief psychotherapy stemming from a model that emphasizes the importance of distorted thoughts and the lack of pleasurable activities in the development of affective disorders. The focus of the therapy can be on either eliminating distorted thought systems or increasing the number of pleasant events that occur on a daily basis, or both. The highly structured therapy presents various skills for patients to learn through class exercises and homework assignments. Older adults respond well to cognitive-behavioral therapy, reporting that they appreciate the structure and the opportunity to learn skills that can help when they are confronted with new stresses. Many also like the focus on here-and-now problems rather than the past. A few treatment modifications are necessary to accommodate community elders complaining of depression. Generally, information must be presented more slowly, taking advantage of multiple modes of presentation. To maintain an active learning process, elder patients should be asked frequently to summarize the material being presented. They should also be given handouts of complex materials and encouraged to maintain notebooks. Other modifications may be required for special populations of older patients.

Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether cognitive function improves with improved glycemic control in older subjects with non-insulin-dependent diabetes (NIDDM). We hypothesized that with improved glycemic control: 1) learning and memory, 2) attention, and 3) complex perceptual-motor function would improve, but that 4) simple perceptual-motor function would not. DESIGN: Non-randomized control trial. SETTING: Aging Study Unit, Department of Veterans Affairs Medical Center. SUBJECTS: Thirty subjects with NIDDM; 17 on oral hypoglycemic agents; 13 untreated at study entry. Thirteen normal controls. INTERVENTION: Subjects on oral hypoglycemic agents were taken off medications. After 1 month, they and previously untreated subjects began treatment with glipizide. Dose was titrated up weekly until fasting plasma glucose was less than 7.8 mmol/L or maximal dose (40 mg/day). Controls received no medication. MEASUREMENTS: Fasting plasma glucose (FPG), glycated hemoglobin, and measures of cognitive function in four general categories: 1) learning and memory, 2) ability to sustain attention, 3) complex perceptual-motor function, and 4) simple perceptual-motor function. All were evaluated in subjects with NIDDM at baseline (T1), after 1-month washout (T2), and after 2 (T3) and 4 months (T4) of optimal glycemic control or maximal dose. Controls were evaluated at the same intervals. RESULTS: FPG and glycated hemoglobin rose in previously treated subjects from T1 to T2 (9.4 +/- SEM 0.4 to 14.7 +/- 0.7 mmol/L and 10.9 +/- 0.7% to 12.2 +/- 0.6%, respectively) but were unchanged in previously untreated subjects (11.3 +/- 0.6 to 11.8 +/- 0.9 mmol/L and 10.9 +/- 0.7% to 11.7 +/- 0.7%). With glipizide treatment, there was a decrease in FPG level at T3 (9.4 +/- 0.5 mmol/L in previously treated, 6.9 +/- 0.4 mmol/L in previously untreated), which persisted at T4. Glycated hemoglobin fell similarly. FPG and glycated hemoglobin were unchanged in controls. As hypothesized, learning and memory improved over time with treatment in both groups of subjects but was unchanged in controls (P < 0.05). Detailed analysis indicated that the improvement occurred primarily in the learning of verbal material. Contrary to hypothesis, attention and complex perceptual-motor function did not show improvement. As expected, simple perceptual-motor function did not show any improvement with treatment. CONCLUSIONS: The results are consistent with previous findings that poor glycemic control in older subjects with NIDDM is associated with decreased cognitive functioning, and suggest that verbal learning and memory may improve with improved glycemic control.

Maintenance of gains versus relapse following brief psychotherapy for depression.

Cross-sectional and longitudinal data are presented from a 2-year follow-up study of 91 older adults, initially diagnosed as in an episode of major depressive disorder (MDD), who were treated with brief cognitive, behavioral, or psychodynamic psychotherapy. Using research diagnostic criteria (RDC), 52%, 58%, and 70% of the sample did not meet criteria for any RDC depressive disorder at posttherapy, and 12- and 24-month follow-ups, respectively. There were no significant differences in response rate by therapy modality. Using Longitudinal Interval Follow-up Evaluation (LIFE; Shapiro & Keller, 1979; Keller et al., 1987) methodology, we noted that patients not depressed at posttreatment remained depression-free for longer time periods than those who were minor or MDD. These rates compare favorably with published reports on younger depressed patients.

Endogenous depression in the elderly: prevalence and agreement among measures.

This article describes agreement among diagnoses made according to five definitions of endogenous depression in a sample of 99 depressed elders and discusses the relationship among these systems and selected demographic and clinical characteristics. Poor to fair agreement was generally demonstrated, except for Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) and Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., rev. (American Psychiatric Association, 1987), which demonstrated excellent agreement. Mostly, demographic and clinical variables (e.g., severity of depression) were unrelated to endogeneity diagnoses. The conclusion was reached that these criteria are not all measuring the same construct in older adults and that the relationship between depression severity and endogeneity should be discussed in terms of specific definitions rather than general terms.

Retrospective assessment of marital adjustment and depression during the first 2 years of spousal bereavement.

Two hundred twelve bereaved elders rated marital adjustment using items drawn from the Locke and Wallace (1959) Marital Adjustment Test and completed the Beck Depression Inventory 2 months, 12 months, and 30 months after the loss of their spouses. Their responses were compared with those of 162 nonbereaved individuals of comparable age who were tested at the same times. More positive ratings of marital adjustment were made by bereaved subjects than by nonbereaved subjects. Among nonbereaved elders, more severe ratings of depression were associated with lower ratings of marital adjustment. In the bereaved sample, however, the opposite was found: More severe ratings of depression were associated with higher ratings of marital adjustment. This pattern of results changed only slightly over the 2.5-year course of bereavement and was not influenced by gender. These results are discussed in terms of cognitive processes (e.g., idealization) that influence retrospective assessments of marital adjustment during bereavement.

The effects of late-life spousal bereavement over a 30-month interval.

Self-report measures of grief, depression, and general psychopathology were studied in widows and widowers over a 2.5-year period following death of their partner. A comparison sample of men and women was also followed for the same period. Differences in severity of depression and psychopathology previously reported at 2 months postloss (Gallagher, Breckenridge, Thompson, & Peterson, 1983) diminished to nonsignificant levels at 12 and 30 months. However, significant differences between bereaved and comparison subjects on measures of grief were still apparent 30 months after spousal loss. A main effect of gender for depression and psychopathology (but not for grief) was found at 2 and 12 months: Women reported more distress than men regardless of bereavement status. Results indicate that the experience of grief persists for at least 30 months in both older men and women who have lost their spouse.

Interaction of depression and bereavement on mental health in the elderly.

Three hundred ninety-three elderly adults aged 55 and older were divided into 1 of 9 subgroups in a 3 (bereavement group: survivors of spouses who died by natural death or by suicide and nonbereaved control Ss) x 3 (depression group: none, mild, and moderate-severe) design over 4 times of measurement--1 month, 6 months, 1 year, and 2.5 years after death of spouse. Significant Bereavement x Depression Group effects were obtained on Brief Symptom Inventory scores. The moderate-severe depression/suicide subgroup had the greatest psychiatric complications with bereavement. Results indicated that elderly persons with significant clinical depression at the time of a spouse's death were at significant risk for psychological complications during the bereavement process, and survivors of spouses who had committed suicide were even more at risk within the greatest depression group.

Auditory averaged evoked potentials and aging: factors of stimulus, task and topography.

The averaged evoked potential to brief tones was compared for 10 young and 10 elderly female subjects. The amplitudes of the sensory components (P1, N1 and P2) were not affected by an infrequent change in pitch of the tones or instructing subjects to count or ignore them; but overall the elderly had a larger P1 and smaller P2 amplitude and a difference in the scalp distribution of P2. Repetition of the tones produced a decrement in these sensory components and a differential one for young and old subjects A slow potential complex consisting of components N2, P3 and SW appeared to changes in tone pitch and became more pronounced when attention was directed to the tones. Overall smaller SPs for oder subjects were interpreted as evidence for a change with age in the cortical representation of the orienting response. Topographical analysis of SPs indicated diminished activity in frontal (Fz) electrodes for elderly persons, suggestive of an enhanced aging process in the frontal cortices.

Prevalence of depression in family caregivers.

Family caregivers who sought help to increase their coping skills (N = 158) and caregivers who volunteered for a longitudinal study of Alzheimer's disease (N = 58) were screened for depression. Among help-seekers, 46% had depression according to Research Diagnostic Criteria (RDC), but among non-help-seekers, only 18% met this criterion. In general, women were more depressed than men, but no major differences in the extent of depression were found in those who cared for more impaired persons.

A comparison of marital interaction patterns between couples in which the husband does or does not have Alzheimer's disease.

UNLABELLED: Objectives. Our main purpose was to examine similarities and differences in patterns of interpersonal interaction between Alzheimer's disease (AD) caregiving and noncaregiving couples (n = 54). Methods. Twenty-seven wives caring for moderately impaired husbands with probable AD and 27 noncaregiving wives from comparable sociodemographic backgrounds were videotaped in their homes during both mealtime and a future event planning task. In addition, they completed self-report questionnaires to assess depression, stress, relationship mutuality, and perceived hope. Results. Compared with their counterparts, caregiving wives reported higher levels of depression and stress, but similar shared values and closeness. For the three factors developed from the Marital Interaction Coding System (MICS, version IV; Supportive Facilitative, and Rapport Building), a complex pattern of results was found in which disease status, type of task, and gender interacted significantly. Noncaregiving couples were more interactive overall and expressed more support to each other. Caregiving wives were found to be most facilitative during the planning task, whereas AD husbands were highest on interactions that built rapport (e.g., smiling) during that same task. Caregiving wives actually increased their facilitative behavior from the mealtime to planning task, probably reflecting the increased demand characteristics of the latter. DISCUSSION: This study is one of a small body of literature to describe the negative impact of AD on spousal communication as observed and coded in two videotaped interaction situations in the home. Suggestions are made for future research, including the inclusion of longitudinal designs and non-Caucasian couples.

Word-to-word variation in ERP component latencies: spoken words.

Data were collected shedding light on the brain electrical activity underlying word recognition. Subjects listened to a list of 48 spoken words in six random orders under two instructional sets: first to "think about the meanings of the words," and second, to learn the list. The scalp EEG associated with hearing and identifying the words was recorded at F3, F4, Cz, P3, P4, Pz, and Oz. Standard within-subjects time-locked averaging across words showed a late negative-positive complex with N2-P3 topography, the negative component peaking around 480 msec, the positive component peaking around 830 msec. Averaging within words across subjects uncovered considerable latency variability in both components. Within-word N2 and P3 component latencies covaried with word durations and with the "recognition points" predicted for the words by the "cohort theory" of word recognition. N2 latencies corresponded closely to the "N400" effect elicited with semantically incongruous sentence-final spoken words. Implications for ERP investigations of language processing are discussed.

An ossifying fibroma of the coronoid process.

We report a case of ossifying fibroma arising from the coronoid process, its influence on the surrounding facial bone growth, and its management.

Physical and psychosocial correlates of hormone replacement therapy with chronically stressed postmenopausal women.

OBJECTIVES: This study investigated the relationship between hormone replacement therapy (HRT) use and physical and psychosocial functioning in a sample of chronically stressed older women. METHODS: Participants (N = 94) were postmenopausal women caring for a parent or spouse with dementia. Caregivers were evaluated using both psychological and physical health indices. RESULTS: Caregivers receiving HRT reported lower levels of hostility and were less likely to report unpleasant interactions with members of their support network; these findings were unrelated to demographic variables, caregiving-related indices, or health behaviors. HRT recipients had lower 10-year risk scores for cardiovascular disease, but there were no group differences in stroke risk. The largest effects on hostility, depression, heart and stroke risk were observed in caregivers receiving a combination of estradiol and progesterone. DISCUSSION: HRT for postmenopausal women may promote positive outcomes for some, but not for all, affective states and cardiovascular variables vulnerable to chronic life stressors.

The dopamine hypothesis of schizophrenia.

While many theories of schizophrenia have been explored, recent research has focused on the possible role that dopamine may play in the causation of this complex disease. After reviewing a clinical description of schizophrenia, this discussion reviews the normal physiology of dopamine, proposed pathological mechanisms, and clinical implications.