The Gray Matters App Targeting Health Behaviors Associated with Alzheimer's Risk: Improvements in Intrinsic Motivation and Impact on Diet Quality and Physical Activity.

OBJECTIVE: We examine if the Gray Matters intervention (education and behavioral self-monitoring app targeting lifestyle risks for Alzheimer's disease [AD]) affected participants' motivation for change and whether high motivation predicts improved diet and physical activity over 6 months. DESIGN: In this 6-month randomized controlled trial (treatment n=104; control n=42; assessed pre/post intervention) amotivation, external regulation, identified regulation, and intrinsic motivation were assessed via the Situational Motivation Scale (SIMS). Diet quality was assessed via adherence to the DASH diet, and physical activity was assessed in minutes. PARTICIPANTS: Eligibility criteria included not having significant cognitive impairment. Participants were aged 39-64 (M = 54.17, SD = 6.9), 66% female, 81% married, 90% White, and 80% had a college degree. INTERVENTION: Treatment included an activity tracker, Gray Matters app, access to booster sessions, contact with a student health coach, and study website. SETTING: Participants were in the general community. RESULTS: Independent samples t-tests determined that intrinsic motivation (IM) increased significantly for the treatment group (M = 2.09 SD = 4.82), compared to the control group (M = 1.00 SD = 5.52; t (130) = -3.04, p = .003). Comparing subgroups of people with High vs Low IM we found that High IM males increased vigorous physical activity more than Lower IM males (F(1,42)=5.053, p=.030). Comparing persons aged 58-64 years with High vs Lower IM, High IM persons had less improvement in diet quality F(1,48)=4.538; p=0.038). CONCLUSION: RCT results support that the Gray Matters AD-focused intervention increased IM, and IM was associated with improved physical activity and diet quality for some subgroups.

Which behavioral and psychological symptoms of dementia are the most problematic? Variability by prevalence, intensity, distress ratings, and associations with caregiver depressive symptoms.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) impact well-being for persons with dementia (PWD) and caregivers. Identifying the most problematic symptoms is vital in targeting interventions and allocating resources. The current study highlights inconsistencies in the "most problematic" symptoms when identified via prevalence, intensity, caregiver distress, or associations with caregiver depressive symptoms. METHODS: Caregivers (N = 177) were mostly female (77%) and spouses of PWD (73%), with average age of 66.7 years (SD = 16.1). They reported BPSD frequency and distress via the Revised Memory and Behavior Problem Checklist (RMBPC) and Neuropsychiatric Inventory (NPI), and their own depressive symptoms via the Geriatric Depression Scale (GDS). BPSD were ranked by prevalence, average frequency, and average distress ratings. RMBPC subscales were correlated with GDS, and discriminant function analyses used NPI symptoms to discriminate between caregivers' normal (range 0-9) or elevated (10+) GDS. RESULTS: Most prevalent NPI symptoms were Apathy, Depression, and Agitation. Most intense (frequency × severity) were Appetite, Motor behaviors, and Apathy, and most distressing were Delusions, Agitation, and Irritability. For RMBPC, Memory was most frequent but least distressing, whereas Disruptive was least frequent but most distressing. RMBPC frequency and distress subscales were significantly associated with caregiver GDS. Discriminant function analyses were statistically significant (Lambda = 0.822; χ(2) (12) = 30.62; p = 0.002. Canonical correlation = 0.442); NPI symptoms correctly classified caregivers GDS status 72% of the time. CONCLUSIONS: Symptoms revealed as "most problematic" varied by measurement criterion. Common or frequent symptoms are not necessarily the most distressing or most predictive of caregiver depression.

Behavioral and psychological symptoms of dementia and caregivers' stress appraisals: intra-individual stability and change over short-term observations.

Dementia is commonly associated with memory loss, but Behavioral and Psychological Symptoms of Dementia (BPSD) such as disruptive behaviors, agitation, and problems with mood, usually have a more significant impact on caregivers' stress. It is known that BPSD and caregivers' stress reactions vary in frequency over the long-term course of dementia, however little is known about the variability over the short-term. The current study included 85 people with dementia and their primary caregivers assessed over three months. Caregivers used a 24-hour log on multiple, consecutive days to report behavioral symptoms of dementia on seven domains of behavior, as well as their stress reactions for each domain. Using latent growth curve analysis, most BPSD and caregiver stress appraisals were found to be, on average, stable over the three-month time frame. For many BPSD and stress appraisal models, however, intra-individual differences in rate of change were significantly different from the mean trend, indicating behaviors and stress are not stable over three months when assessed at the level of the individual. Covariates were used to explain individual differences in rates of change; however few variables were significantly associated with intra-individual short-term change over time.

Mutagenic and cytotoxic effectiveness of zinc dimethyl and zinc diisononyldithiocarbamate in human lymphocyte cultures.

The mutagenic and cytotoxic effectiveness of the vulcanisation accelerators zinc dimethyldithiocarbamate (ZDMC; ziram) and zinc diisononyldithiocarbamate (ZDINDC; arbestab Z) was tested in lymphocyte cultures of five healthy probands. ZDMC and ZDINDC (c=0.1, 1.0 and 10.0microg/ml) were studied in lymphocyte cultures without external metabolic activation. Additionally, incubation of the compounds (c=10.0microg/ml) was performed in the presence of liver microsomes from aroclor-induced rats (1 and 2h, 1 and 2mg microsomal protein). Genotoxicity testing was performed by analysis of chromosomal aberrations (CA), sister chromatid exchanges (SCEs) and micronuclei (MN). For evaluation of antiproliferative effects, mitotic index (MI) and cell cycle kinetics (CCK) were determined. In contrast to earlier investigations we found no significantly increased mutagenic or cytotoxic activity of ZDMC; ZDINDC also was inactive under these conditions.

Chromosome painting reveals specific patterns of chromosome occurrence in mitomycin C- and diethylstilboestrol-induced micronuclei.

Cultures of human blood lymphocytes from three subjects were incubated with the clastogen mitomycin C (MMC, 500 ng/ml) and the aneugen diethylstilboestrol (DES, 80 microM) 23 h before harvesting, to induce formation of micronuclei (MN) and numerical and structural alterations in metaphase chromosomes. We used fluorescence in situ hybridization (FISH) with painting probes for all human chromosomes to determine which chromosomes had contributed material to the induced MN. MMC treatment induced an approximately 18-fold increase in MN and led to a significant increase in hypodiploidy and structural chromosome aberrations in metaphase preparations. Undercondensation of pericentromeric heterochromatin of chromosomes 9 and 1 occurred in 20-75% of metaphases and FISH disclosed an abundance of material from these chromosomes in induced MN (62-69% from chromosome 9 and 7-12% from chromosome 1). DES treatment of lymphocytes induced a seven-fold increase in MN frequency and four-fold increase in the frequency of numerical aberrations; structural aberrations were not significantly increased. FISH analysis showed that material from all chromosomes was present in DES-induced MN, with material from chromosome 1 present in 16% of MN and material from each other chromosomes being present in 2-10% of MN. Material from chromosomes 14, 19 and 21 was significantly more frequent material from chromosome Y significantly less frequent in DES-treated cells than in controls. The findings of the MMC studies indicate that the heterochromatin block of chromosome 9 is a specific target for MMC-induced undercondensation, which induces a preferential occurrence of chromosome 9 material in MN. DES, in contrast, does not trigger heterochromatin decondensation and fails to induce such a significant appearance of material of particular chromosomes in MN.

Comparison of spontaneous and idoxuridine-induced micronuclei by chromosome painting.

Fluorescence in situ hybridisation (FISH) technique with chromosome specific library (CSL) DNA probes for all human chromosomes were used to study about 9000 micronuclei (MN) in normal and idoxuridine (IUdR)-treated lymphocyte cultures of female and male donors. In addition, MN rates and structural chromosome aberrations were scored in Giemsa-stained chromosome spreads of these cultures. IUdR treatment (40 microg/ml) induced on the average a 12-fold increase of the MN rate. Metaphase analysis revealed no distinct increase of chromosome breaks but a preferential decondensation at chromosome 9q12 (28-79%) and to a lower extend at 1q12 (8-21%). Application of FISH technique with CSL probes to one male and one female untreated proband showed that all human chromosomes except chromosome 12 (and to a striking high frequency chromosomes 9, X and Y) occurred in spontaneous MN. In cultures containing IUdR, the chromosomal spectrum found in MN was reduced to 10 chromosomes in the male and 13 in the female proband. Eight chromosomes (2, 6, 12, 13, 14, 15, 17 and 18) did not occur in MN of both probands. On the contrary chromosomes 1 and especially 9 were found much more frequently in the MN of IUdR-treated cultures than in MN of control cultures. DAPI-staining revealed heterochromatin signals in most of the IUdR-induced MN. In an additional study, spontaneous and IUdR-induced MN were investigated in lymphocytes of another female donor using CSL probes only for chromosomes 1, 6, 9, 15, 16 and X. The results confirmed the previous finding that chromosomes 1 and 9 occur very often in MN after IUdR-treatment. The results indicate that decondensation of heterochromatic regions on chromosomes 1 and 9 caused by IUdR treatment strongly correlates with MN formation by these chromosomes.

Frequencies of occurrence of all human chromosomes in micronuclei from normal and 5-azacytidine-treated lymphocytes as revealed by chromosome painting.

Chromosome painting with library DNA probes specific for all human chromosomes was used to study the chromosomal content of micronuclei (MN) in normal and 5-azacytidine (5-aza-C)-treated lymphocyte cultures. More than 60,000 normal lymphocytes were screened for associated MN after in situ hybridization. At least 50 MN were scored for each probe. With the exception of chromosomes 12 and 19, which did not occur in MN, all other chromosomes were detected in MN at frequencies varying from 1 to 11.5%. Treatment of lymphocyte cultures with 5-aza-C induced preferential exclusion of chromosomes 1 (34%), 9 (32%) and 16 (20%) material in MN, whereas chromosome 8, 10, 12-15 and 21 material was not detected in MN. The results obtained from normal lymphocytes allow for the first time an estimation of the frequency of occurrence of all chromosomes in spontaneously occurring MN in human cells. Data derived from 5-aza-C-treated lymphocytes are furthermore consistent with the view that undermethylation of heterochromatin may be associated with loss of specific chromosomes at metaphase.

[Clinical feature and histopathology of v. Hippel-Lindau's disease (author's transl)]. / Klinik und Histopathologie der v. Hippel-Lindauschen Erkrankung

A case of familial v. Hippel-Lindau's disease is described. Both clinical symptomatology and histological changes, not only of the eye but also of other organs are considered and the findings are compared with reports in the literature.