The relevance of hippocampal subfield integrity and clock drawing test performance for the diagnosis of Alzheimer’s disease and mild cognitive impairment

<p><b>Objectives:</b> The clock drawing test (CDT) is one of the worldwide most used screening tests for Alzheimer’s disease (AD). MRI studies have identified temporo-parietal regions being involved in CDT impairment. However, the contributions of specific hippocampal subfields and adjacent extrahippocampal structures to CDT performance in AD and mild cognitive impairment (MCI) have not been investigated so far. It is unclear whether morphological alterations or CDT score, or a combination of both, are able to predict AD.</p> <p><b>Methods:</b> 38 AD patients, 38 MCI individuals and 31 healthy controls underwent neuropsychological assessment and MRI at 3 Tesla. FreeSurfer 5.3 was used to perform hippocampal parcellation. We used a collection of statistical methods to better understand the relationship between CDT and hippocampal formation. We also tested the clinical feasibility of this relationship when predicting AD.</p> <p><b>Results:</b> Impaired CDT performance in AD was associated with widespread atrophy of the cornu ammonis, presubiculum, and subiculum, whereas MCI subjects showed CDT-related alterations of the CA4-dentate gyrus and subiculum. CDT correlates in AD and MCI showed regional and quantitative overlap. Importantly, CDT score was the best predictor of AD.</p> <p><b>Conclusions:</b> Our findings lend support for an involvement of different hippocampal subfields in impaired CDT performance in AD and MCI. CDT seems to be more efficient than subfield imaging for predicting AD.</p

The relevance of hippocampal subfield integrity and clock drawing test performance for the diagnosis of Alzheimerâs disease and mild cognitive impairment

10nonenoneHirjak, Dusan; Sambataro, Fabio; Remmele, Barbara; Kubera, Katharina M.; Schrã¶der, Johannes; Seidl, Ulrich; Thomann, Anne K.; Maier-hein, Klaus H.; Wolf, Robert C.; Thomann, Philipp A.Hirjak, Dusan; Sambataro, Fabio; Remmele, Barbara; Kubera, Katharina M.; Schrã¶der, Johannes; Seidl, Ulrich; Thomann, Anne K.; Maier hein, Klaus H.; Wolf, Robert C.; Thomann, Philipp A

The impact of memory concerns on the risk of future Alzheimer's Dementia is moderated by objective memory performance at baseline.

<p><i>Note</i>. The impact of memory concerns on the risk of future Alzheimer's Dementia, expressed in terms of the Hazard Ratio (HR) for the predictor “memory concerns”, is plotted as a function of objective memory performance at baseline, i.e. the interaction effect between memory concerns and objective memory performance is depicted. Values are derived from the multivariate Cox-proportional Hazard Regression analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100812#pone-0100812-t001" target="_blank">Table 2</a>, model step 3: HR of the interaction-term  = 1.51, 95% Confidence Interval: 1.01–2.25). The black solid line corresponds to the estimated HR-value  = 1.51 of the interaction effect. The two dotted lines represent the functional curves that result when the boundary HR-values of the lower 95% Confidence Interval ( = 1.01) or upper 95% Confidence Interval ( = 2.25) respectively, are inserted as numbers to plot the interaction effect. CERAD-DR  =  Delayed Recall of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery.</p

Risk of incident Alzheimer's Dementia: Results from hierarchically formulated multivariate Cox proportional hazard regression models.

<p><i>Note</i>. M2LL of the Intercept model  = 830.6. Details of the modeling process are given in the methods section. The HR for the CERAD-DR is below one as it represents the HR for a one unit increase in CERAD-DR scores (i.e. for better memory performance). Lower CERAD-DR scores are therefore associated with a higher risk of developing incident AD. B  =  Beta-Coefficient of the predictor, CI  =  Confidence Interval, CERAD-DR  =  Delayed Recall of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery, HR  =  Hazard Ratio, M2LL  =  Minus-Two-Log-Likelihood, MC  =  Memory Concerns, SE  =  Standard Error for B.</p