Background: Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression.

Methods: This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating – sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI).

Results: Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β = –1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01).

Conclusions: Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.

The regional distribution of degeneration of the corpus callosum (CC) in dementia is not yet clear. This study compared regional CC size in participants (n = 179) from the Cache County Memory and Aging Study. Participants represented a range of cognitive function: Alzheimer's disease (AD), vascular dementia (VaD), mild ambiguous (MA–cognitive problems, but not severe enough for diagnosis of dementia), and healthy older adults. CC outlines obtained from midsagittal magnetic resonance images were divided into 99 equally spaced widths. Factor analysis of these callosal widths identified 10 callosal regions. Multivariate analysis of variance revealed significant group differences for anterior and posterior callosal regions. Post-hoc pairwise comparisons of CC regions in patient groups as compared to the control group (controlling for age) revealed trends toward smaller anterior and posterior regions, but not all were statistically significant. As compared to controls, significantly smaller anterior and posterior CC regions were found in the AD group; significantly smaller anterior CC regions in the VaD group; but no significant CC regional differences in the MA group. Findings suggest that dementia-related CC atrophy occurs primarily in the anterior and posterior portions. (JINS, 2008, 14, 414–423.)

Objective: To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD).

Methods: The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status.

Results: One or more NPS were observed in 51% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR = 4.76, p = 0.02), depression (OR = 3.87, p = 0.03), and apathy (OR = 4.48, p = 0.02). Hypertension was associated with increased risk of delusions (OR = 2.34, p = 0.02), anxiety (OR = 4.10, p = 0.002), and agitation/aggression (OR = 2.82, p = 0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health.

Conclusions: Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions.

We examined asymmetry of hippocampal volume as well as other temporal lobe structures (temporal lobe, temporal horn of the lateral ventricular system, parahippocampal and fusiform gyri) in 194 subjects from the Cache County, Utah study, with varying disorders [85 with Alzheimer's disease (AD), 59 with some cognitive or neuropsychiatric disorder—referenced as a Mixed Neuropsychiatric group, 30 with mild ambiguous/mild cognitive impairment (MA/MCI) and 20 controls] and APOE genotypes. Asymmetry was determined by subtracting left-side volume from the right corrected by total intracranial volume. No significant asymmetry was observed to be associated with presence of the ε4 allele. Since the AD-ε4 allele risk effect may be expressed early in the course of the disorder, we also examined asymmetry indices in AD, MA/MCI and Mixed Neuropsychiatric subjects early in the course of their disorder (2 years or less) to those with longer duration illness (greater than 2 years). We observed a leftward asymmetry (i.e., left side larger) regardless of APOE genotype in hippocampal volume where both AD and MCI subjects demonstrated a leftward shift in hippocampal size when length of disease (LOD) was less but not more than 2 years. Leftward asymmetry was not associated with LOD in the Mixed Neuropsychiatric group. These findings do not support an association between ε4 and hippocampal asymmetry in dementia. We also examined whether asymmetry influenced neuropsychological performance, but minimal effects were observed. Where significance or strong trends were observed, better neuropsychological performance was associated with larger parenchymal volume of temporal lobe structures. These findings were interpreted as representing cognitive reserve effects where larger volume was protective against impairment. The role of asymmetry research in understanding neuropsychological performance in dementia is discussed. (JINS, 2002, 8, 925–933.)