Cognitive impairment is a common non-motor symptom in Parkinson’s Disease (PD) and an important source of patient disability and caregiver burden. The timing, profile and rate of cognitive decline varies widely among individuals with PD and can range from normal cognition to mild cognitive impairment (PD-MCI) and dementia (PDD). Beta-amyloid and tau brain accumulation, oxidative stress and neuroinflammation are reported risk factors for cognitive impairment. Traumatic brain injury and pesticide and tobacco exposure have also been described. Genetic risk factors including genes such as COMT, APOE, MAPT and BDNF may also play a role. Less is known about protective factors, although the Mediterranean diet and exercise may fall in this category. Nonetheless, there is conflicting evidence for most of the factors that have been studied. The use of inconsistent criteria and lack of comprehensive assessment in many studies are important methodological issues. Timing of exposure also plays a crucial role, although identification of the correct time window has been historically difficult in PD. Our understanding of the mechanism behind these factors, as well as the interactions between gene and environment as determinants of disease phenotype and the identification of modifiable risk factors will be paramount, as this will allow for potential interventions even in established PD.

Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research. The most established magnetic resonance imaging (MRI) finding is hippocampal atrophy, which is related to memory decline and currently used as a diagnostic criterion for AD. While the medial temporal lobes are impacted early by the spread of neurofibrillary tangles, other networks and regional changes can be found quite early in the progression. Atrophy in several frontal and parietal regions, cortical thinning, and white matter alterations correlate with memory deficits in early AD. Changes in activation and connectivity have been detected by functional MRI (fMRI). Task‐based fMRI studies have revealed medial temporal lobe hypoactivation, parietal hyperactivation, and frontal hyperactivation in AD during memory tasks, and activation patterns of these regions are also altered in preclinical and prodromal AD. Resting state fMRI has revealed alterations in default mode network activity related to memory in early AD. These studies are limited in part due to the historic inclusion of patients who had suspected AD but likely did not have the disorder. Modern biomarkers allow for more diagnostic certainty, allowing better understanding of neuroimaging markers in true AD, even in the preclinical stage. Larger patient cohorts, comparison of candidate imaging biomarkers to more established biomarkers, and inclusion of more detailed neuropsychological batteries to assess multiple aspects of memory are needed to better understand the memory deficit in AD and help develop new biomarkers. This article reviews MRI findings related to episodic memory impairments in AD and introduces a new study with multimodal imaging and comprehensive neuropsychiatric evaluation to overcome current limitations.

Lateralization of default mode network (DMN) functioning has been shown to change with age. Similarly, lateralization of frontal lobe function has been shown to decline in age. The impact of amyloid pathology and the progression of Alzheimer’s disease (AD) on resting state lateralization has not been investigated. Due to the preferential involvement of the left hemisphere in verbal tasks, there may be a benefit to higher levels of left-lateralization in the performance of verbal memory tasks. Here we compared functional lateralization of the anterior and posterior DMN between four groups of participants: amyloid negative (Aβ-) and amyloid positive (Aβ+) groups with normal cognition (NC), and Aβ+ groups with mild cognitive impairment (Aβ+MCI) or dementia (Aβ+AD). Differences were evident between groups in posterior DMN; the Aβ-NC group was more left-lateralized than both cognitively impaired Aβ+ groups. There was no difference in anterior DMN. No differences in overall network connectivity between groups were observed, suggesting that the functional lateralization finding is not secondary to general changes in connectivity. Left-lateralization of both networks was associated with better verbal recall performance. Older subjects, overall, had less left functional lateralization of the anterior DMN.

Introduction Sex differences in dementia with Lewy bodies (DLB) have been reported in clinically defined cohorts; however, clinical diagnostic accuracy in DLB is suboptimal and phenotypic differences have not been assessed in pathologically confirmed participants. Methods Core DLB features were compared across 55 women and 156 men with pathologically defined DLB in the National Alzheimer’s Coordinating Center. These analyses were repeated for 55 women and 55 men matched for age, education and tau burden. Results In the total sample, women died older, had fewer years of education, had higher tau burden but were less likely to be diagnosed with dementia and clinical DLB. In the matched sample, visual hallucinations continued to be less common in women, and fewer women met clinical DLB criteria. Discussion Sex impacts clinical manifestations of underlying pathologies in DLB. Despite similar underlying Lewy body pathology, women are less likely to manifest core DLB features and may be clinically underdiagnosed.

More than half of the patients with Alzheimer’s disease (AD) have comorbidities including TDP-43 and Lewy bodies, which are also associated with frontotemporal lobar degeneration and dementia with Lewy bodies, respectively. These comorbidities may help explain the overlapping neuropsychiatric symptoms between AD and other dementias. Data on 221 AD patients with Neuropsychiatric Inventory-Questionnaire were obtained from the National Alzheimer’s Coordinating Center. TDP-43 was associated with aberrant motor activity, whereas Lewy bodies were associated with anxiety, irritability, sleep behavior, and appetite problems. The associations between these comorbidities and neuropsychiatric symptoms were more significant for patients with sparse diffuse plaques.