Confronting Alzheimer's Disease Risk in Women: A Feasibility Study of Memory Screening as Part of the Annual Gynecological Well-Woman Visit.

Objective: Routine health care visits offer the opportunity to screen older adults for symptoms of Alzheimer's disease (AD). Many women see their gynecologist as their primary health care provider. Given this unique relationship, the Women's Preventive Services Initiative and the American College of Obstetrics and Gynecology advocate for integrated care of women at all ages. It is well-established that women are at increased risk for AD, and memory screening of older women should be paramount in this effort. Research is needed to determine the feasibility and value of memory screening among older women at the well-woman visit. Materials and Methods: Women aged 60 and above completed a 5-item subjective memory screener at their well-woman visit at the Columbia University Integrated Women's Health Program. Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation. Rates of positive screens, item endorsement, and referral preferences were examined. Results: Of the 530 women approached, 521 agreed to complete the screener. Of those, 17.5% (n = 91) were classified as positive. The most frequently endorsed item was difficulty with memory or thinking compared with others the same age. Among women with positive screens, 57.5% were interested in pursuing clinical referrals to a memory specialist. Conclusion: Results support the feasibility and potential value of including subjective memory screening as part of a comprehensive well-woman program. Early identification of memory loss will enable investigation into the cause of memory symptoms and longitudinal monitoring of cognitive change.

Demographic and Symptom Correlates of Initial Idiopathic Psychiatric Diagnosis in Frontotemporal Dementia.

INTRODUCTION: This study aims to measure frequency and correlates of initial idiopathic psychiatric diagnosis in a cohort of 147 patients with Frontotemporal Dementia (FTD)-spectrum disorders. METHODS: Participants were evaluated at the National Institutes of Health in Bethesda, Maryland. Initial participant diagnoses were determined by chart review and patient and informant interviews. Logistic regression was used to assess the relationships between diagnosis and age of symptom onset, gender, education, family history of psychiatric illness, and family history of dementia. Additional exploratory analyses investigated patients' first symptom type. RESULTS: 25% (n=43) of all the patients reviewed were initially misdiagnosed with an idiopathic psychiatric illness, which is less than half the commonly cited 50% rate.3 Depression was the most common misdiagnosis (46.5%). Family history of dementia, family history of mental illness and an exploratory analysis of behavioral first symptoms suggested significant association with a greater likelihood of initial idiopathic psychiatric diagnosis in FTD patients. DISCUSSION: This data confirms patterns of initial idiopathic psychiatric diagnosis in FTD and elucidates potential factors underlying misdiagnosis. Potential implications for patient outcomes, caregiver burden and healthcare costs are discussed.

The association of vasomotor symptoms during the menopausal transition and cognition in later life.

OBJECTIVE: The majority of women experience vasomotor symptoms (VMS) during the menopausal transition. Whether self-reported VMS are associated with cognitive test performance later in life remains unclear. The goal of this study was to determine whether a greater burden of VMS is associated with poor later-life cognition. METHODS: The Wisconsin Longitudinal Study is a prospective study of randomly selected Wisconsin high school graduates of the class of 1957. At ages 65 and 72, a random subset of participants completed six cognitive tests, including similarities, letter and category fluency, immediate and delayed word recall, and digit ordering. Nested regression models were used to examine the association between extent of VMS, assessed at age 54, and baseline cognition at 65, adjusting for early-life socioeconomic status, women's reproductive health variables, intelligence quotient, and midlife income. This series of models was also used to examine the association between VMS and change in cognition score from age 65 to 72. In sensitivity analyses, models were repeated in a sample using multiple imputation for missing covariates. RESULTS: Of the 5,326 women enrolled, 874 had data onVMS, covariates, and all cognitive tests. In an unadjusted model, higher VMS were associated with a lower similarities score (b = -0.09 95% CI -0.16 to -0.02) at age 65 but no other cognitive tests. In adjusted models, VMS were not related to cognition at age 65 or change in cognition. Results remained similar with multiple imputation. CONCLUSIONS: Our study does not support a relationship between self-reported VMS and cognition later in life.

Proposed research criteria for prodromal behavioural variant frontotemporal dementia.

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed 'mild behavioural and/or cognitive impairment in bvFTD' (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer's disease, and the false positive rate of diagnosis was 11-16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

Association Between Early Psychotic Symptoms and Alzheimer's Disease Prognosis in a Community-Based Cohort.

BACKGROUND: Psychotic symptoms are an important and increasingly recognized aspect of Alzheimer's disease (AD). They have been shown to contribute to faster disease progression in clinic-based, demographically homogenous samples with high educational attainment. OBJECTIVE: We studied the association between baseline psychotic symptoms and disease progression among individuals with incident AD or 'at risk' of developing AD, from a demographically heterogenous, community-based cohort with minimal educational attainment. METHODS: 212 participants received the Columbia University Scale of Psychopathology in Alzheimer's Disease scale. Participants had psychotic symptoms with any of: visual illusions, delusions, hallucinations, or agitation/aggression. Disease progression was measured yearly and defined by meeting cognitive (≤10 on the Folstein MMSE) or functional endpoints (≥10 on the Blessed Dementia Rating Scale or ≥4 on the Dependence Scale). RESULTS: The mean age was 85 years old. The cohort was 78.3% female, 75.9% Hispanic, and had a mean 6.96 years of education. Within the follow-up period (mean: 3.69 years), 24 met the cognitive endpoint, 59 met the functional endpoint, and 132 met the cutoff for dependence. The presence of at least one psychotic symptom was initially associated with an increased risk of reaching the functional endpoint (HR 3.12, 95% CI 1.67-5.86, p < 0.001) and the endpoint of dependence (HR = 1.498, 95% CI 1.05-2.13, p = 0.03). However, these associations were attenuated and non-significant when adjusted for baseline functional status. Psychotic symptoms were not associated with the cognitive endpoint. CONCLUSION: Psychotic symptoms may predict functional decline in patients of non-Caucasian ethnicity and with lower educational attainment.

The Phenomenology of Acute Anosognosia for Hemiplegia.

OBJECTIVE: After attempting to move a plegic limb, patients with anosognosia for hemiplegia (AHP) may claim that limb movement occurred, even though the limb remained motionless. The authors investigated the characteristics, natural history, and anatomical basis of AHP phenomenology. METHODS: Twenty-nine right-hemisphere stroke patients with acute anosognosia for hemiplegia (AHP) were prospectively assessed for the presence and characteristics of movement claims and observable behavior during movement attempts. RESULTS: AHP was transient, with the condition resolving in 68% of patients by 1 week. Patients made movement claims during 31% of unilateral movement attempts and 50% of bilateral movement attempts. Movement claims were idiosyncratic, lacked internal consistency within individual patients, and even dissociated from explicit denial, as several patients made movement claims after they began to explicitly acknowledge hemiplegia. Observable behavior during movement attempts revealed allochiria (moving the right arm instead of the left) in 31% of patients, signs of implicit knowledge of weakness in 24%, and intact intention in 34%. Lesion analysis revealed that allochiria was associated with inferior right parietal lobe damage. CONCLUSIONS: These results highlight that heterogeneity, phenomenological complexity, and transience are hallmarks of AHP. This advances clinical AHP assessment by showing that assessment of performance, rather than just verbal response, uncovers multiple dimensions of AHP. Allochiria emerges as an anatomically distinct subcomponent of the disorder. These findings also have theoretical implications, because they do not lend support to unitary pathogenic models proposing that illusions of movement or impaired intention form the basis of AHP. Most patients rapidly improve, which should invigorate the search for typical compensatory mechanisms underlying spontaneous recovery.

Behavioral and Psychiatric Symptoms of Dementia and Rate of Decline in Alzheimer's Disease.

Alzheimer's disease causes both cognitive and non-cognitive symptoms. There is increasing evidence that the presentation and course of Alzheimer's disease is highly heterogenous. This heterogeneity presents challenges to patients, their families, and clinicians due to the difficulty in prognosticating future symptoms and functional impairment. Behavioral and psychiatric symptoms are emerging as a significant contributor to this clinical heterogeneity. These symptoms have been linked to multiple areas of neurodegeneration, which may suggest that they are representative of network-wide dysfunction in the brain. However, current diagnostic criteria for Alzheimer's disease focus exclusively on the cognitive aspects of disease. Behavioral and psychiatric symptoms have been found in multiple studies to be related to disease severity and to contribute to disease progression over time. A better understanding of how behavioral and psychiatric symptoms relate to cognitive aspects of Alzheimer's disease would help to refine the models of disease and hopefully lead to improved ability to develop therapeutic options for this devastating disease.

Picture-Based Memory Impairment Screen: Effective Cognitive Screen in Ethnically Diverse Populations.

OBJECTIVES: To describe the psychometric properties of the Picture-based Memory Impairment Screen (PMIS) in a multidisciplinary memory disorder center serving an ethnically and educationally diverse community. DESIGN: Cross-sectional cohort study. SETTING: Montefiore Center for Aging Brain (CAB) PARTICIPANTS: Individuals with cognitive complaints (N=405; average age 76±10, 66% female). MEASUREMENTS: A geriatrician or neurologist administered the PMIS, and a neuropsychologist administered the Blessed Information, Memory, and Concentration (BIMC) test and determined whether participants had dementia, mild cognitive impairment (MCI), or subjective cognitive complaints (SCC). RESULTS: Mean PMIS scores were 4.0±2.6 in participants with dementia (n=194), 6.8±1.5 in those with MCI (n= 155), and 7.0±1.8 in those with SCC (n= 56) (p<.001). PMIS scores showed similar significant linear trends when analyzed according to ethnicity, education, sex, and language. The PMIS was negatively correlated with BIMC score (p<.001). The PMIS had positive predictive value of 77%, negative predictive value of 73%, sensitivity of 68%, and specificity of 81% to detect all-cause dementia in this population of individuals with cognitive complaints. CONCLUSION: The PMIS is a quick, valid screening tool to identify cognitive impairment in individuals with cognitive complaints that accounts for cultural and educational differences.

Limb Misidentification: A Clinical-Anatomical Prospective Study.

The misidentification of one's own limb (LM) after right hemisphere stroke is a striking phenomenon that is incompletely understood. The authors prospectively studied the natural history and anatomy of LM in 36 patients with hyperacute right middle cerebral artery infarct. Unlike in previous studies, rapid clinical assessment was prioritized. The authors found LM to be common and transient, involving 61% at onset, evolving to 15% at 1 week. Voxel-based lesion-symptom mapping found supramarginal gyrus (SMG) damage associated with LM. This substantiates the SMG's importance in LM and has broader implications for lesion analysis: timing matters. Rapid assessment of transient disorders minimizes false negatives, which can improve lesion analysis.

Theaflavin-3-gallate and theaflavin-3'-gallate, polyphenols in black tea with prooxidant properties.

This study compared the in vitro responses of human gingival fibroblasts and of carcinoma cells derived from the tongue to theaflavin-3-gallate (TF-2A) and theaflavin-3'-gallate (TF-2B), polyphenols in black tea. The antiproliferative and cytotoxic effects of the theaflavin monomers were more pronounced to the carcinoma, than to the normal, cells. In phosphate buffer at pH 7.4, the theaflavins generated hydrogen peroxide and the superoxide anion, suggesting that their mode of toxicity may be due, in part, to the induction of oxidative stress. In a cell-free assay, TF-2A and TF-2B reacted directly with reduced glutathione (GSH), in a time- and concentration-dependent manner. Intracellular storages of GSH were depleted on treatment of the cells with the theaflavin monomers. Depletion of intracellular GSH was more extensive with TF-2A than with TF-2B and was more pronounced in the carcinoma, than in the normal, cells. The toxicities of the theaflavins were potentiated when the cells were cotreated with the GSH depleter, d,l-buthionine-[S,R]-sulfoximine. In the presence of catalase, pyruvate and divalent cobalt, all scavengers of reactive oxygen species, the cytotoxicities of the theaflavins were lessened. TF-2A and TF-2B induced lipid peroxidation in the carcinoma cells, whereas in the fibroblasts, peroxidation was evident upon exposure to TF-2A, but not to TF-2B. These studies demonstrated that the black tea theaflavin monomers, TF-2A and TF-2B, act as prooxidants and induce oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.