Molly E. Zimmerman

White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network

White matter hyperintensities (WMHs) are areas of increased signal on T2‐weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimers disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD.

The effect of white matter hyperintensities on neurodegeneration in mild cognitive impairment

It is unclear whether white matter hyperintensities (WMHs), magnetic resonance imaging markers of small‐vessel cerebrovascular disease, promote neurodegeneration and associated clinical decline in Alzheimers disease (AD), or simply co‐occur with recognized pathogenic processes.

Symptoms from repeated intentional and unintentional head impact in soccer players

Objective: To determine the rate and differential contribution of heading vs unintentional head impacts (e.g., head to head, goal post) to CNS symptoms in adult amateur soccer players. Methods: Amateur soccer players completed baseline and serial on-line 2-week recall questionnaires (HeadCount) and reported (1) soccer practice and games, (2) heading and unintentional soccer head trauma, and (3) frequency and severity (mild to very severe) of CNS symptoms. For analysis, CNS symptoms were affirmed if one or more moderate, severe, or very severe episodes were reported in a 2-week period. Repeated measures logistic regression was used to assess if 2-week heading exposure (i.e., 4 quartiles) or unintentional head impacts (i.e., 0, 1, 2+) were associated with CNS symptoms. Results: A total of 222 soccer players (79% male) completed 470 HeadCount questionnaires. Mean (median) heading/2 weeks was 44 (18) for men and 27 (9.5) for women. One or more unintentional head impacts were reported by 37% of men and 43% of women. Heading-related symptoms were reported in 20% (93 out of 470) of the HeadCounts. Heading in the highest quartile was significantly associated with CNS symptoms (odds ratio [OR] 3.17, 95% confidence interval [CI] 1.57–6.37) when controlling for unintentional exposure. Those with 2+ unintentional exposures were at increased risk for CNS symptoms (OR 6.09, 95% CI 3.33–11.17) as were those with a single exposure (OR 2.98, 95% CI 1.69–5.26) when controlling for heading. Conclusions: Intentional (i.e., heading) and unintentional head impacts are each independently associated with moderate to very severe CNS symptoms.

Differential association of left and right hippocampal volumes with verbal episodic and spatial memory in older adults.

The hippocampus plays a critical role in verbal and spatial memory, thus any pathological damage to this formation may lead to cognitive impairment. It is suggested that right and left hippocampi are affected differentially in healthy or pathologic aging. The purpose of this study was to test the hypothesis that verbal episodic memory performance is associated with left hippocampal volume (HV) while spatial memory is associated with right HV. 115 non-demented adults over age 70 were drawn from the Einstein Aging Study. Verbal memory was measured using the free recall score from the Free and Cued Selective Reminding Test - immediate recall (FCSRT-IR), logical memory immediate and delayed subtests (LM-I and LM-II) from the Wechsler Memory Scale-Revised (WMS-R). Spatial Memory was measured using a computerized dot memory paradigm that has been validated for use in older adults. All participants underwent 3T MRI with subsequent automatized measurement of the volume of each hippocampus. The sample had a mean age of 78.7 years (SD=5.0); 57% were women, and 52% were white. Participants had a mean of 14.3 years (SD=3.5) of education. In regression models, two tests of verbal memory (FCSRT-IR free recall and LM-II) were positively associated with left HV, but not with right HV. Performance on the spatial memory task was associated with right HV, but not left HV. Our findings support the hypothesis that the left hippocampus plays a critical role in episodic verbal memory, while right hippocampus might be more important for spatial memory processing among non-demented older adults.

Daytime somnolence as an early sign of cognitive decline in a community‐based study of older people

This study aimed to examine the association between self‐reported sleep problems and cognitive decline in community‐dwelling older people. We hypothesized that daytime somnolence predicts subsequent cognitive decline.

Comparison of "Word" vs. "Picture" version of the Free and Cued Selective Reminding Test (FCSRT) in older adults

This study examined the psychometric relationship between the Word and Picture versions of the Free and Cued Selective Reminding Test (FCSRT) and developed an equation for score conversion.

Roles of hippocampal subfields in verbal and visual episodic memory

HighlightsNeurocognitive tests tapping specific HC subfields can help target at‐risk individuals.Subiculum was associated with verbal and visual episodic memory.CA1 was associated with verbal and visual episodic memory.No other subfields were associated with verbal or visual episodic memory.Our results suggest that CA1 and subiculum are responsible for retrieval. Introduction: Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer’s disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. Methods: This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community‐based study of non‐demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2‐CA3, CA4‐dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. Results: Participants had a mean age of 78.9 (SD = 5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (&bgr; = 0.31, p = 0.001) and FCSRT Delayed Recall (&bgr; = 0.27, p = 0.007); subiculum volume was associated with Complex Figure Delayed Recall (&bgr; = 0.27, p = 0.002) and FCSRT Delayed Recall (&bgr; = 0.24, p = 0.010); CA1 was associated with Complex Figure Delayed Recall (&bgr; = 0.26, p < 0.002) and FCSRT Delayed Recall (&bgr; = 0.20, p = 0.025). Conclusions: Our findings confirm previous research on the specific roles of CA1 and subiculum in episodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory.

Sleep Disordered Breathing and White Matter Hyperintensities in Community-Dwelling Elders.

STUDY OBJECTIVES To examine the association between markers of sleep-disordered breathing (SDB) and white matter hyperintensity (WMH) volume in an elderly, multiethnic, community-dwelling cohort. METHODS This is a cross-sectional analysis from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a community-based epidemiological study of older adults. Structural magnetic resonance imaging was obtained starting in 2004; the Medical Outcomes Study-Sleep Scale (MOS-SS) was administered to participants starting in 2007. Linear regression models were used to assess the relationship between the two MOS-SS questions that measure respiratory dysfunction during sleep and quantified WMH volume among WHICAP participants with brain imaging. RESULTS A total of 483 older adults had both structural magnetic resonance imaging and sleep assessment. Self-reported SDB was associated with WMH. After adjusting for demographic and vascular risk factors, WMH volumes were larger in individuals with frequent snoring (β = 2.113, P = 0.004) and among those who reported waking short of breath or with headache (β = 1.862, P = 0.048). CONCLUSIONS In community-dwelling older adults, self-reported measures of SDB are associated with larger WMH volumes. The cognitive effects of SDB that are increasingly being recognized may be mediated at the small vessel level.

Perceived Stress Is Differentially Related to Hippocampal Subfield Volumes among Older Adults

Introduction Chronic exposure to stress has been shown to impact a wide range of health-related outcomes in older adults. Despite extensive animal literature revealing deleterious effects of biological markers of stress on the dentate gyrus subfield of the hippocampus, links between hippocampal subfields and psychological stress have not been studied in humans. This study examined the relationship between perceived stress and hippocampal subfield volumes among racially/ethnically diverse older adults. Methods and Materials Between July 2011 and March 2014, 116 nondemented participants were consecutively drawn from the Einstein Aging Study, an ongoing community-based sample of individuals over the age of 70 residing in Bronx, New York. All participants completed the Perceived Stress Scale, Geriatric Depression Scale, and underwent 3.0 T MRI. FreeSurfer was used to derive total hippocampal volume, hippocampal subfield volumes (CA1, CA2/CA3, CA4/Dentate Gyrus (CA4/DG), and subiculum), entorhinal cortex volume, whole brain volume, and total intracranial volume. Results Linear regression analyses revealed that higher levels of perceived stress were associated with smaller total hippocampal volume (β = -0.20, t = -2.40, p = 0.02), smaller CA2/CA3 volumes (β = -0.18, t = -2.24, p = 0.03) and smaller CA4/DG volumes (β = -0.19, t = -2.28, p = 0.03) after controlling for total intracranial volume, age, gender, and race. These findings remained unchanged after removal of individuals with clinically significant symptoms of depression. Discussion Our findings provide evidence of a relationship between a direct indicator of psychological stress and specific hippocampal subfield volumes in elderly individuals. These results highlight the importance of clinical screening for chronic stress in otherwise healthy older adults.

Memory Binding Test Distinguishes Amnestic Mild Cognitive Impairment and Dementia from Cognitively Normal Elderly

Objective We aimed to assess reliability and cross-sectional discriminative validity of the Memory Binding Test (MBT) to distinguish persons with amnestic cognitive impairment (aMCI) and dementia from cognitively normal elderly controls. Method The MBT was administered to 20 participants with dementia, 31 with aMCI and 246 controls, who received the first administration of the MBT from May 2003 to December 2007, as a substudy of the community-based Einstein Aging Study (age range: 70+). The optimal index resulted from comparing the partial area under the receiver operating characteristic curves (ROC AUC) of four major MBT indices for specificities ≥0.70. Optimal cut-score of the optimal index was selected by maximizing the sum of sensitivity and specificity. Age and education effects were assessed using stratified cut-scores and adjusted logistic regression. Reliability was computed as intraclass correlation between scores at baseline and 1-year follow-up for participants who remained cognitively normal. Results Total number of Items recalled in the Paired condition (TIP) was elected the optimal index. TIP cut-score was ⩽22 for differentiating aMCI alone (sensitivity = 0.74, specificity = 0.73) and aMCI and dementia combined (sensitivity = 0.84, specificity = 0.73) from controls. It was ⩽17 for differentiating dementia from aMCI and controls (sensitivity = 0.95, specificity = 0.87). Age and education adjustments did not materially improve discriminative validity. The reliability of TIP was 0.77. Conclusions MBT achieved moderate to good reliability. TIP had superior cross-sectional discriminative validity than the other MBT indices. We recommend using the empirical cut-score of TIP ⩽22 for discriminating aMCI and dementia and ⩽17 for discriminating dementia alone.