Non-memory Cognitive Domains Research Articles

5 Cognitive, Emotional, and Functional Predictors of Clinical Trial Enrollment

Objective:With participant recruitment being a top barrier to AD research progress, the rate of screen failure in Alzheimer’s disease (AD) clinical trials is unsustainable. Although steps have been undertaken to consider solutions to the continued recruitment shortage, there is unfortunately minimal emphasis on reducing screen failure rates based on study inclusion criteria. Here we present information attempting to understand the cognitive, emotional, and functional features of individuals who failed screening measures for AD trials.Participants and Methods:The current study is a retrospective, cross-sectional analysis. Thirty-eight participants (aged 50-83) having (1) previously received a clinical diagnostic workup at a transdisciplinary cognitive specialty clinic and (2) previously screened for a specific industry-sponsored clinical trial of MCI/early AD (EMERGE) met inclusion criteria. Previously collected clinical data were analyzed to identify predictors of AD trial screen pass/fail status.Results:Of the 38 participants in the current study, 14 screen passed into this AD clinical trial, and 24 screen failed. Higher screen failure rates were significantly related to gender, with 83% of female participants screen failing this AD trial versus 45% of male participants. There was no difference in age or education between screen pass/fail groups, nor were differences present for performance on visual or verbal memory tasks, or the MOCA. Conversely, those participants screen failing this AD clinical trial performed significantly worse on nonmemory cognitive domains pertaining to general fund of knowledge, working memory, and executive functioning. Additionally, the screen fail group reported greater levels of anxiety, but not depression nor endorsements on a measure of functional status.Conclusions:Worse performance on non-memory neuropsychological domains was related to screen failure status for the EMERGE AD clinical trial. This finding may be explained by the traditional recruitment pathway from clinic to trials, which beyond the diagnosis of interest is up to the opinion of the physician to determine “fit” for a trial. Higher screen failure rates may result from physicians erroneously viewing more globally-impaired patients as being more appropriate for an AD clinical trial, resulting in greater tendencies towards recruiting patients who are too severe to meet inclusion criteria for a trial. Recruiting patients into clinical trials earlier in their disease course - when disease severity is less - may result in reduced screen failure rates in AD trials. That we could not detect a relationship between memory-related tasks and screen fail/pass status may be explained by either (1) the measures used in the EMERGE trial were not as sensitive to subtle changes in memory, or (2) that memory dysfunction is necessary for a diagnosis of AD but not sufficient to distinguish who will be successfully screened into an AD clinical trial. Overall, these findings have the potential to advance the field by reducing screen failure rates in AD clinical trials by using information already available to clinical trial teams, which will enhance trial-recruitment infrastructure and encourage greater engagement of older adults in AD research.

Clinical and Neuropsychological Correlates of Prefrailty Syndrome.

Physical frailty is closely associated with cognitive impairment. We aim to investigate the neuropsychological profiles of prefrail and non-frail dementia-free community-dwelling older adults using a comprehensive neuropsychological evaluation, and to examine the association between specific frailty criteria and clinical and neuropsychological scores. Participants completed a comprehensive standardized neuropsychological evaluation (covering cognitive domains such as memory, executive functions, language and attention), and frailty assessment. Frailty was assessed according to biological criteria: unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. The sample comprised 60 dementia-free community-dwelling adults, aged 65 years or older (range 65–89 years; 60.0% women). Forty-two participants were classified as robust (no frailty criteria present), and 18 as prefrail (1 or 2 frailty criteria present). We explored neurocognitive differences between the groups and examined the association between specific criteria of frailty phenotype and clinical and neuropsychological outcomes with bivariate tests and multivariate models. Prefrail participants showed poorer cognitive performance than non-frail participants in both memory and non-memory cognitive domains. However, delayed episodic memory was the only cognitive subdomain that remained significant after controlling for age, gender, and educational level. Gait speed was significantly associated with general cognitive performance, immediate memory, and processing speed, while grip strength was associated with visual episodic memory and visuoconstructive abilities. Both gait speed and grip strength were negatively associated with depressive scores. Our results suggest that prefrailty is associated with cognitive dysfunction. The fact that specific cognitive domains may be susceptible to subclinical states of physical frailty may have important clinical implications. Indeed, early detection of specific cognitive dysfunctions may allow opportunities for reversibility.

Non-memory subjective cognitive concerns predict incident motoric cognitive risk syndrome.

Motoric cognitive risk syndrome (MCR) is a predementia condition that combines slow gait and subjective cognitive concerns. As the earliest markers of MCR are relatively unknown, the role of subjective cognitive concerns was investigated to predict incident MCR in a well-characterized prospective cohort of non-demented older adults. Non-demented MCR-free older adults (n=476) from the Central Control of Mobility in Aging cohort completed gait, subjective cognition and neuropsychological assessment at baseline and follow-up. Subjective concerns were analyzed via responses to 12 items from three validated measures, the Late-Life Function and Disability Instrument - Disability Component, the Activities of Daily Living Prevention Instrument and the Geriatric Depression Scale, and were independent of items utilized to diagnose MCR. Cox proportional hazard models examined the association between cognitive concerns and incident MCR. After 2.36±1.4years, 28 participants developed MCR. Executive functioning (adjusted hazard ratio 2.458, 95% confidence interval 1.094-5.524, P=0.029) and mental clarity concerns (adjusted hazard ratio 3.917, 95% confidence interval 1.690-9.077, P=0.001) were associated with incident MCR, controlling for age, sex, education and gait speed. Subjective cognitive concerns in non-memory cognitive domains predict incident MCR. Although most MCR studies assess cognitive concerns about memory, our findings suggest the need to broaden the scope of subjective cognitive assessment to enhance the accuracy of diagnosis and prediction of future cognitive decline.

Prodromal Dementia With Lewy Bodies: Clinical Characterization and Predictors of Progression

ObjectiveThe objective of this study was to examine clinical characteristics, cognitive decline, and predictors for time to dementia in prodromal dementia with Lewy bodies with mild cognitive impairment (MCI‐LB) compared with prodromal Alzheimer's disease (MCI‐AD).MethodsWe included 73 MCI‐LB patients (12% female; 68 ± 6 years; Mini Mental State Examination, 27 ± 2) and 124 MCI‐AD patients (48% female; 68 ± 7 years; Mini Mental State Examination, 27 ± 2) from the Amsterdam Dementia Cohort. Follow‐up was available for 61 MCI‐LB patients and all MCI‐AD patients (3 ± 2 years). We evaluated dementia with Lewy bodies core features, neuropsychiatric symptoms, caregiver burden (Zarit caregiver burden interview), MRI, apolipoprotein genotype, and cerebrospinal fluid biomarkers (tau/Aβ1–42 ratio). Longitudinal outcome measures included cognitive slopes (memory, attention, executive functions, and language and visuospatial functions) and time to dementia.ResultsParkinsonism was the most frequently present core feature in MCI‐LB (69%). MCI‐LB patients more often had neuropsychiatric symptoms and scored higher on ZARIT when compared with the MCI‐AD patients. Linear mixed models showed that at baseline, MCI‐LB patients performed worse on nonmemory cognitive domains, whereas memory performance was worse in MCI‐AD patients. Over time, MCI‐LB patients declined faster on attention, whereas MCI‐AD patients declined faster on the Mini Mental State Examination and memory. Cox proportional hazards regressions showed that in the MCI‐LB patients, lower attention (hazard ratio [HR] = 1.6; 95% confidence interval [CI], 1.1–2.3) and more posterior cortical atrophy (HR = 3.0; 95% CI, 1.5–5.8) predicted shorter time to dementia. In the MCI‐AD patients, worse performance on memory (HR = 1.1; 95% CI, 1.0–1.2) and executive functions (HR = 1.3; 95% CI, 1.0–1.6) were independently associated with time to Alzheimer's dementia.ConclusionMCI‐LB patients have distinct neuropsychiatric and cognitive profiles with prominent decline in attention when compared with MCI‐AD patients. Our results highlight the importance of early diagnosis because symptoms already have an impact in the prodromal stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Cross-sectional associations between [18F]GTP1 tau PET and cognition in Alzheimer's disease

The regional relationships between tau positron emission tomography (PET) imaging and cognitive impairment in Alzheimer's disease (AD) remain uncertain. We examined cross-sectional associations between cognitive performance, cerebral uptake of the novel tau PET tracer [18F]GTP1, and other neuroimaging indices ([18F]florbetapir amyloid PET, magnetic resonance imaging) in 71 participants with normal cognition, prodromal AD, or AD dementia. Greater [18F]GTP1 uptake was seen with increasing clinical severity and correlated with poorer cognition. [18F]GTP1 uptake and cortical volume (but not [18F]florbetapir uptake) were independently associated with cognitive performance, particularly within the temporal lobe. Delayed memory was more specifically associated with temporal [18F]GTP1 uptake; other domains correlated with a broader range of regional [18F]GTP1 uptake. These data confirm that [18F]GTP1 tau PET uptake significantly correlates with cognitive performance in AD, but regional correlations between performance in non-memory cognitive domains were less specific than reported by tau PET imaging studies that included participants with atypical focal cortical AD syndromes. Tau PET imaging may have utility as a surrogate biomarker for clinical AD progression in therapeutic trials of disease-modifying interventions.

Timely Detection of Mild Cognitive Impairment in Italy: An Expert Opinion

Mild cognitive impairment (MCI) generally evolves in a gradually progressive decline in memory and non-memory cognitive domains that may eventually decay to dementia. This process might be preventable by improving early detection of the MCI syndrome followed by proper and timely interventions. The aim of this work was providing helpful indications for a standardized early diagnosis of MCI, mainly focusing on the Italian elderly population. We reviewed here MCI epidemiology and classification, as well as the most recent advancements in early detection of the patient with MCI in the Italian scenario. Specialist centers in connection with general practitioners (GPs) have been established across the country and designated as Centers for Cognitive Disorders and Dementia (CDCD). CDCDs are dedicated to the diagnosis and management of patients for all forms of dementia across all the complex staging spectrum. New tools were made available by the advancements of imaging techniques and of the research on biomarkers, leading to novel approaches based on the combination of imaging and biomarker detection, to improve accuracy and effectiveness in the early diagnosis of MCI. Moreover, patient genotyping, alone or in combination with other techniques, was also revealed as a promising method in evaluating and preventing MCI progression. We recommend the introduction of all these novel tools in the diagnostic practice of the specialist centers and that further efforts and resources are spent into the research of the most effective techniques and biomarkers to be introduced as first-level tests into the practice of early diagnosis of MCI.

Associations between sleep duration and cognitive impairment in mild cognitive impairment

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. A subsample of 271 participants with a diagnosis of probable Alzheimer's disease (AD; N=50) or mild cognitive impairment (MCI; N=121) and 100 persons who were not cognitively impaired (NI) were recruited from a large population-based cohort in the island of Crete, Greece (3140 older adults aged >60years). All participants underwent extensive neuropsychiatric/neuropsychological evaluation and a 3-day 24-hr actigraphy. Objective sleep variables and their association with neuropsychological performance were examined across the three groups, controlling for demographics, body mass index, depression, sleep apnea symptoms and psychotropic medications. Patients with AD had significantly longer 24-hr total sleep time (TST) compared to the MCI and NI groups. Long 24-hr TST was associated with reduced performance on tasks that placed significant demands on attention and processing speed in the MCI group and the AD group. Elderly patients with MCI have similar objective sleep duration to normal controls, whereas AD patients sleep longer. Long sleep duration in patients with multidomain subtypes of MCI is associated with critical non-memory cognitive domains. It appears that within the MCI group those that sleep longer have more severe cognitive impairment.

Neuropsychological, Psychiatric, and Functional Correlates of Clinical Trial Enrollment.

Screen failure rates in Alzheimer's disease (AD) clinical trial research are unsustainable, with participant recruitment being a top barrier to AD research progress. The purpose of this project was to understand the neuropsychological, psychiatric, and functional features of individuals who failed screening measures for AD trials. Previously collected clinical data from 38 patients (aged 50-83) screened for a specific industry-sponsored clinical trial of MCI/early AD (Biogen 221AD302, [EMERGE]) were analyzed to identify predictors of AD trial screen pass/fail status. Worse performance on non-memory cognitive domains like crystalized knowledge, executive functioning, and attention, and higher self-reported anxiety, was associated with failing the screening visit for the EMERGE AD clinical trial, whereas we were not able to detect a relationship between screening status and memory performance, self-reported depression, or self-reported daily functioning. By identifying predictors of AD trial screen passing/failure, this research may influence decision-making about which patients are most likely to successfully enroll in a trial, thereby potentially lowering participant burden, maximizing study resources, and reducing costs.

Correlates of recognition memory performance in amnestic mild cognitive impairment

ABSTRACTIntroduction: Determining whether the etiology of amnestic Mild Cognitive Impairment (aMCI) is Alzheimer’s disease (AD) is challenging. Recognition memory (RM) performance could be helpful in identifying individuals with cognitive patterns indicative of underlying AD. In order to better identify such patterns, we examined RM discriminability in aMCI and its associations with nonmemory cognitive domains impaired in AD.Methods: Participants were 97 individuals diagnosed with aMCI (Mage = 74.48 years) who underwent comprehensive neuropsychological evaluation. Zero-order correlations and hierarchical linear regression analyses were conducted to determine associations between discriminability on the HVLT-R and specific tasks within the domains of executive function (EF) and language, controlling for age and education. Logistic regression was conducted to determine whether performance on individual tasks was predictive of group membership defined as impaired or unimpaired on RM performance.Results: While 100% of the aMCI group showed impaired delayed recall on a word list, we found that 69% were impaired on RM discriminability, while 31% were not. Discriminability impairment groups did not differ on demographics or global cognition. For the entire aMCI group, performance in the language domain and, specifically, on a confrontation naming task significantly predicted RM discriminability. Confrontation naming was predictive of RM impairment group membership.Conclusions: Our results demonstrate individuals with aMCI are heterogeneous and show variability in RM discriminability. RM performance was associated with measures of language, elucidating patterns of cognition potentially marking those more likely to progress to AD. Future studies need to address this finding in a longitudinal sample.

Distinct subtypes of Alzheimer\u2019s disease based on patterns of brain atrophy: longitudinal trajectories and clinical applications

Atrophy patterns on MRI can reliably predict three neuropathological subtypes of Alzheimer’s disease (AD): typical, limbic-predominant, or hippocampal-sparing. A method to enable their investigation in the clinical routine is still lacking. We aimed to (1) validate the combined use of visual rating scales for identification of AD subtypes; (2) characterise these subtypes at baseline and over two years; and (3) investigate how atrophy patterns and non-memory cognitive domains contribute to memory impairment. AD patients were classified as either typical AD (n = 100), limbic-predominant (n = 33), or hippocampal-sparing (n = 35) by using the Scheltens’ scale for medial temporal lobe atrophy (MTA), the Koedam’s scale for posterior atrophy (PA), and the Pasquier’s global cortical atrophy scale for frontal atrophy (GCA-F). A fourth group with no atrophy was also identified (n = 30). 230 healthy controls were also included. There was great overlap among subtypes in demographic, clinical, and cognitive variables. Memory performance was more dependent on non-memory cognitive functions in hippocampal-sparing and the no atrophy group. Hippocampal-sparing and the no atrophy group showed less aggressive disease progression. Visual rating scales can be used to identify distinct AD subtypes. Recognizing AD heterogeneity is important and visual rating scales may facilitate investigation of AD heterogeneity in clinical routine.

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly--Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe).

ObjectiveSubjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality.MethodsData were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD.ResultsAmong 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset.ConclusionIncident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

Early onset APOE E4-negative Alzheimer’s disease patients show faster cognitive decline on non-memory domains

Age at onset and APOE E4-genotype have been shown to influence clinical manifestation of Alzheimer’s disease (AD). We investigated rate of decline in specific cognitive domains according to age at onset and APOE E4-genotype in patients with AD. 199 patients with probable AD underwent at least two annual neuropsychological assessments. Patients were classified according to age-at-onset (≤65 years vs >65 years) and APOE genotype (positive vs negative). The neuropsychological test battery compromised tests for memory, language, attention, executive and visuo-spatial functioning. For each domain compound z-scores were calculated, based on the baseline performance of patients. Average duration of follow-up was 1.5±1 years. We used linear mixed models (LMM) to estimate effects of age, APOE and age⁎APOE on cognitive decline over time. At baseline, patients were 65±8 years, 98(49%) were female and MMSE was 22±4. LMM showed that early onset patients declined faster on executive functioning (β±SE:−0.09±0.06) than late onset patients, but age was not related to decline in the other cognitive domains. APOE E4 negative patients declined faster on language than APOE E4 positive patients (β±SE:−0.1±0.06). When we took age and APOE genotype into account simultaneously, we found that compared to late onset-E4 positive patients, early onset-E4 negative patients declined faster on language (β±SE:−0.36±0.1), attention (β±SE:−0.42±0.1), executive (β±SE:−0.41±0.1) and visuo-spatial functioning (β±SE:−0.43±0.1). Late onset-E4 negative and early onset-E4 positive patients showed intermediate rates of decline. We found no differences in decline on memory. We found that patients who develop AD despite absence of the two most important risk factors, show steepest cognitive decline on non-memory cognitive domains.

The Sub-Classification of Amnestic Mild Cognitive Impairment Using MRI-Based Cortical Thickness Measures.

Background: Amnestic mild cognitive impairment (aMCI) is considered to be the transitional stage between healthy aging and Alzheimer’s disease (AD). Moreover, aMCI individuals with additional impairment in one or more non-memory cognitive domains are at higher risk of conversion to AD. Hence accurate identification of the sub-types of aMCI would enable earlier detection of individuals progressing to AD.Methods: We examine the group differences in cortical thickness between single-domain and multiple-domain sub-types of aMCI, and as well as with respect to age-matched controls in a well-balanced cohort from the Sydney Memory and Aging Study. In addition, the diagnostic value of cortical thickness in the sub-classification of aMCI as well as from normal controls using support vector machine (SVM) classifier is evaluated, using a novel cross-validation technique that can handle class-imbalance.Results: This study revealed an increased, as well as a wider spread, of cortical thinning in multiple-domain aMCI compared to single-domain aMCI. The best performances of the classifier for the pairs (1) single-domain aMCI and normal controls, (2) multiple-domain aMCI and normal controls, and (3) single and multiple-domain aMCI were AUC = 0.52, 0.66, and 0.54, respectively. The accuracy of the classifier for the three pairs was just over 50% exhibiting low specificity (44–60%) and similar sensitivity (53–68%).Conclusion: Analysis of group differences added evidence to the hypothesis that multiple-domain aMCI is a later stage of AD compared to single-domain aMCI. The classification results show that discrimination among single, multiple-domain sub-types of aMCI and normal controls is limited using baseline cortical thickness measures.

Visuo-spatial memory tests in right temporal lobe epilepsy foci: Clinical validity

ObjectiveTo examine the appropriateness of visual memory tests as an identification method for right mesial temporal lobe dysfunctions in an epilepsy patient group and to study the relationship and possible overlap with non-memory cognitive domains and demographic variables. MethodsEighty preoperative candidates with mesial temporal lobe epilepsy (TLE) were examined using the “Corsi Block-Tapping Test”, “Diagnosticum für Cerebralschädigung” (DCS), the path subtest of the “Verbaler und Visueller Merkfähigkeitstest” (VVM), and the Rey-Osterrieth Complex Figure Test (ROCF). Factorial analyses were performed on raw scores to determine the effect of epilepsy–related variables, interictal epileptiform discharges (IEDs) and presence of cortical dysgenesis, on visual and verbal memory parameters. Sensitivity, specificity and Receiver Operating Characteristic (ROC) curves were calculated based on normative data. Furthermore, Spearman correlations between memory and non-memory cognitive tasks were performed. ResultsThe scores for test sensitivity and specificity and the ROC curves illustrate the tests' poor capacity to lateralize the functional deficit zone even when epilepsy–related factors, such as cortical dysgenesis or presence of contralateral IEDs were controlled. Significant correlations were found between the visual memory measures and nonverbal reasoning, processing speed, attentional flexibility, and visual planning. ConclusionThese neuropsychological tests are not sensitive enough to lateralize the epileptogenic focus in temporal lobe epilepsy patients since in addition to learning and consolidation processes, they measure additional cognitive domains. These results have implications for clinical neuropsychologists, in terms of test choice and the interpretation in the context of presurgical diagnostics.

Subjective complaints in mild cognitive impairment make a difference

Subjective complaints in mild cognitive impairment make a difference

Thalamic atrophy and cognition in unilateral temporal lobe epilepsy

This study examined quantitative magnetic resonance volumes of the thalamus and hippocampus and determined their relationship with cognitive function and clinical seizure characteristics in a sample of 46 unilateral temporal lobe epilepsy (TLE) subjects (20 left and 26 right) and 29 controls. The hippocampus and thalamus exhibited different patterns of volume abnormality, different associations with clinical seizure characteristics, and different patterns of relationship with cognitive measures. Hippocampal volume reduction was primarily ipsilateral to the seizure focus, and thalamic volume reduction was bilateral. Ipsilateral hippocampal volume was significantly correlated with both early neurodevelopmental features (age of seizure onset) and disease characteristics (duration of epilepsy), whereas thalamus integrity was related only to disease variables. Hippocampal volume showed a selective association with verbal memory performance. In contrast, both left and right thalamic volumes were significantly correlated with performance on both memory and nonmemory cognitive domains. These findings underscore the importance of thalamic atrophy in chronic TLE and its potential implications for cognition.

-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease

Beta-amyloid (Abeta) deposition is pathognomic for Alzheimer's disease (AD), but may occur in normal elderly people without apparent cognitive effect. Episodic memory impairment is an early and prominent sign of AD, but its relationship with Abeta burden in non-demented persons and in AD patients is unclear. We examined this relationship using 11C-PIB-PET as a quantitative marker of Abeta burden in vivo in healthy ageing (HA), mild cognitive impairment (MCI) and AD. Thirty-one AD, 33 MCI and 32 HA participants completed neuropsychological assessment and a 11C-PIB-PET brain scan. Multiple linear regression analyses were conducted relating episodic memory performance and other cognitive functions to Abeta burden. Ninety-seven percent of AD, 61% of MCI and 22% of HA cases had increased cortical PIB binding, indicating the presence of Abeta plaques. There was a strong relationship between impaired episodic memory performance and PIB binding, both in MCI and HA. This relationship was weaker in AD and less robust for non-memory cognitive domains. Abeta deposition in the asymptomatic elderly is associated with episodic memory impairment. This finding, together with the strong relationship between PIB binding and the severity of memory impairment in MCI, suggests that individuals with increased cortical PIB binding are on the path to Alzheimer's disease. The data also suggests that early intervention trials for AD targeted to non-demented individuals with cerebral Abeta deposition are warranted.

A Clinical Approach to Mild Cognitive Impairment

A Clinical Approach to Mild Cognitive Impairment

Hippocampal Volume Is Associated with Memory but not Nonmemory Cognitive Performance in Patients with Mild Cognitive Impairment

Mild cognitive impairment (MCI) appears to be a transitional stage in the development of Alzheimer's disease (AD). Patients with MCI show impaired memory performance and hippocampal atrophy relative to normal elderly controls. Prior studies indicate that the degree of hippocampal atrophy in MCI patients predicts conversion to AD. In contrast to patients with MCI who have deficits primarily in memory, AD patients have clinically evident impairments in both memory and nonmemory cognitive domains. One explanation for the observation that a smaller hippocampal volume predicts conversion to AD might be that hippocampal atrophy is associated with early impairment in nonmemory cognitive areas as well as memory. A link between hippocampal volume and nonmemory function could occur if hippocampal atrophy was correlated with AD pathology in other brain regions. We therefore sought to determine the relationship of hippocampal volume with performance on memory and nonmemory tasks in patients with MCI. Although we found a significant correlation between hippocampal volume and memory performance, we did not find a significant correlation between hippocampal volume and nonmemory performance. We conclude that the relationship between hippocampal volume and risk of AD is likely tied to reduced memory performance and not associated with impairment in nonmemory cognitive domains.