Depression, cognitive, and functional outcomes of Problem Adaptation Therapy (PATH) in older adults with major depression and mild cognitive deficits.

OBJECTIVES: Antidepressants have limited efficacy in older adults with depression and cognitive impairment, and psychosocial interventions for this population have been inadequately investigated. Problem Adaptation Therapy (PATH) is a psychosocial intervention for older adults with major depression, cognitive impairment, and disability. DESIGN: This study tests the efficacy of PATH versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in reducing depression (Montgamery Asberg Depression Rating Scale [MADRS]) and disability (World Health Organization Disability Assessments Schedule-II [WHODAS-II]) and improving cognitive outcomes (Mini Mental State Examination [MMSE]) over 24 weeks (12 weeks of treatment and 12-week post-treatment follow-up). SETTING: Participants were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry. Both interventions and all research assessments were conducted at home. PARTICIPANTS: Thirty-five older adults (age ≥ 65 years) with major depression and cognitive impairment no dementia (CIND). INTERVENTIONS: PATH aims to increase emotion regulation by incorporating a problem-solving approach, teaching compensatory strategies, and inviting caregiver participation. Supportive Therapy aims to facilitate the expression of affect, as well as promote empathy. MEASUREMENTS: Depression was measured using the MADRS, disability using the WHODAS-II, and cognition using the MMSE. RESULTS: PATH participants showed significantly greater reduction in MADRS total score (7.04 points at 24 weeks, treatment group by time interaction: F[1,24.4] = 7.61, p = 0.0108), greater improvement in MMSE total score (2.30 points at 24 weeks, treatment group by time interaction: F[1,39.8] = 13.31, p = 0.0008), and greater improvement in WHODAS-II total score (2.95 points at 24 weeks, treatment group by time interaction: F[1,89] = 4.93, p = 0.0290) than ST-CI participants over the 24-week period. CONCLUSIONS: PATH participants had better depression, cognitive, and disability outcomes than ST-CI participants over 6 months. PATH may provide relief to depressed older adults with CIND who currently have limited treatment options.

Development and psychometric evaluation of the Test of Practical Judgment alternate form (Form B).

The Test of Practical Judgment (TOP-J) is increasingly used by neuropsychologists to measure everyday judgment ability in older adulthood. In the present study, we developed an alternate TOP-J Form B, which may be used to reduce practice effects for repeat assessment situations or in place of the original Form A. In developing the measure, special attention was given to limiting cultural bias and making items similar in content and difficulty to Form A. The TOP-J Form B was piloted in a clinical geriatric sample (N = 77) in the Midwestern U.S. Subsequently, older adults (N = 130) were recruited from several boroughs of New York City and surrounding areas (mean age = 77; mean years of education = 16; 69% female; 28% Black/African-American, 11% Hispanic). In this validation sample, both the 9-item and 15-item versions of the TOP-J Form B showed strong psychometric properties, including good unidimensional model fit in confirmatory factor analysis, preliminary convergent/divergent and criterion validity evidence, and strong inter-rater reliability, ICC (2, 1) = .93. The means and standard deviations for the TOP-J Form A and Form B were highly similar, particularly for the 9-item forms in which there was less than a one-point mean difference. Preliminary normative data for cognitively intact participants (n = 73) were established. We present means and standard deviations that will allow for the calculation of z scores as Form B scores were normally distributed. The newly developed TOP-J Form B should be useful in diverse clinical and research settings.

Informant report of practical judgment ability in a clinical sample of older adults with subjective cognitive decline, mild cognitive impairment, and dementia.

Despite the importance of capturing problems with judgment and decision-making during neuropsychological evaluations of older adults, there are a limited number of validated measures and no informant rating scales. We developed an informant measure that captures compromised judgment related to safety, medical, financial, and social-ethical issues After item refinement and piloting in a memory disorders clinic, we utilized the Test of Practical Judgment-Informant (TOP-J-Informant) at two clinics in the Midwestern U.S., including 189 patient/informant dyads (mean age = 79.0, median years of education = 13, % female = 67.7) with various preclinical and clinical dementia conditions. We found psychometric support, including evidence for convergent, divergent, and criterion-related validity, and internal consistency. Importantly, we were able to discriminate between diagnostic groups in the expected direction. The TOP-J-Informant is brief (<5 minutes), easy to administer, and can reveal areas of concern related to poor judgment when administered in the context of a neuropsychological evaluation or clinic visit.

Re-evaluation of psychometric evidence and update of normative data for the Test of Practical Judgment.

ObjectiveThe Test of Practical Judgment (TOP-J) has shown utility in inpatient and outpatient settings in older adults who present with mild cognitive impairment and various dementia subtypes. The TOP-J has two versions (i.e. 9 items and 15 items), and was initially validated within a small rural non-Hispanic White sample. In the current study, we re-evaluated the psychometric evidence and refined scoring criteria and administration guidelines in older adults with more diverse demographic characteristics than the original validation sample. Method: Participants (N = 348) were recruited from several boroughs of New York City and surrounding areas (mean/median age = 79; mean years education = 15, median = 15.5; 68% female; 30% Black/African-American, 8% Hispanic). Results: Reliability and validity were comparable to original findings. Based on confirmatory factor analysis, one item was replaced on the 9-item version, now called TOP-J Form A. Normative data for cognitively intact participants (n = 261) were updated and stratified by two education groups. Conclusions: The TOP-J is increasingly used in clinical and research settings in the U.S. and abroad, and the current study provides improved normative data and administration and scoring guidelines for use with demographically diverse older individuals.

Predicting mental health help seeking orientations among diverse Undergraduates: An ordinal logistic regression analysis✰.

BACKGROUND: Recent years have seen a steady increase in college students reporting mental health issues, though only approximately one-third of these students seek treatment. The present study examines: a) students' perceptions of access to campus provided mental health care; b) student stigma attitudes based on social distance and willingness to disclose mental health issues to campus members who might support help-seeking efforts; and c) the predictive value of five factors (aged older than 22, female gender, completed two or more psychology courses, low stigma, and high perception of access) on help-seeking orientation (HSO). METHODS: We performed an ordinal logistic regression (OLR) on data from a diverse sample of undergraduates (n = 1,272). The OLR statistical model is more appropriate for measurement of Likert style data than commonly employed statistical models, which may oversimplify attitudinal data by assuming equal intervals between response categories. RESULTS: Most students did not know that campus-provided counseling was free or confidential, and almost half did not perceive these services as timely or adequate. Students reported more stigma related to disclosing their own problems than to supporting someone else. All five study predictors retained positive and statistically significant slope associations with a positive HSO. Unexpectedly, we found a statistically significant gender interaction with psychology coursework. LIMITATIONS: Data were obtained through self-report measures. CONCLUSIONS: Results are discussed in relation to the possibility that campus-based mental health interventions may remove roadblocks to healthy help-seeking behaviors, particularly for male students.

Associations of lifestyle and vascular risk factors with Alzheimer's brain biomarker changes during middle age: a 3-year longitudinal study in the broader New York City area.

OBJECTIVE: To investigate the associations between lifestyle and vascular risk factors and changes in Alzheimer's disease (AD) biomarkers (beta-amyloid load via 11C-PiB PET, glucose metabolism via 18F-FDG PET and neurodegeneration via structural MRI) and global cognition in middle-aged asymptomatic participants at risk for AD. DESIGN: Prospective, longitudinal. SETTING: The study was conducted at New York University Langone/Weill Cornell Medical Centres in New York City. PARTICIPANTS: Seventy cognitively normal participants from multiple community sources, aged 30-60 years with lifestyle measures (diet, intellectual activity and physical activity), vascular risk measures and two imaging biomarkers visits over at least 2 years, were included in the study. OUTCOME MEASURES: We examined MRI-based cortical thickness, fluoro-deoxy-glucose (FDG) glucose metabolism and PiB beta-amyloid in AD-vulnerable regions. A global cognitive z-score served as our summary cognition measure. We used regression change models to investigate the associations of clinical, lifestyle and vascular risk measures with changes in AD biomarkers and global cognition. RESULTS: Diet influenced changes in glucose metabolism, but not amyloid or cortical thickness changes. With and without accounting for demographic measures, vascular risk and baseline FDG measures, lower adherence to a Mediterranean-style diet was associated with faster rates of FDG decline in the posterior cingulate cortex (p≤0.05) and marginally in the frontal cortex (p=0.07). None of the other lifestyle variables or vascular measures showed associations with AD biomarker changes. Higher baseline plasma homocysteine was associated with faster rates of decline in global cognition, with and without accounting for lifestyle and biomarker measures (p=0.048). None of the lifestyle variables were associated with cognition. CONCLUSIONS: Diet influenced brain glucose metabolism in middle-aged participants, while plasma homocysteine explained variability in cognitive performance. These findings suggest that these modifiable risk factors affect AD risk through different pathways and support further investigation of risk reduction strategies in midlife.

Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area.

OBJECTIVE: To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN: Cross-sectional, observational. SETTING: Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS: We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition. RESULTS: Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: ßs≥0.26, insulin sensitivity ßs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (ßs≥0.25 P≤0.001), as were those between overweight and lower cognition (ßs≥-0.22, P≤0.01). CONCLUSIONS: In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.

Correction: Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery.

[This corrects the article DOI: 10.1371/journal.pone.0185926.].

Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.

OBJECTIVE: To examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain ß-amyloid load via 11C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife. METHODS: Seventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally. RESULTS: MeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions (p < 0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group (pinteraction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD. CONCLUSION: Lower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD.

Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.

OBJECTIVE: This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men. METHODS: Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined. All patients had volumetric MRI, 18F-fluoro-2-deoxyglucose (FDG)-PET (glucose metabolism), and Pittsburgh compound B-PET scans (ß-amyloid [Aß] deposition, a hallmark of AD pathology). RESULTS: As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased Aß deposition, and reduced gray and white matter volumes in AD-vulnerable regions (p < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women (p < 0.001). Aß deposition was exacerbated in APOE4-positive MENO women relative to the other groups (p < 0.001). CONCLUSIONS: Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.

Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery.

After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's<0.001). A gradient in biomarker abnormalities was most pronounced in MENO, intermediate in PERI, and lowest in CNT (p<0.001). Biomarkers correlated with immediate and delayed memory scores (Pearson's 0.26≤r≤0.32, p≤0.05). These findings validate earlier preclinical findings and indicate emergence of bioenergetic deficits in perimenopausal and postmenopausal women, suggesting that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.