Objective: Leukoaraiosis (LA) refers to white matter changes (WMC) which are neuroimaging indicators of small vessel disease. The Leukoaraiosis And DISability (LADIS) study (2009) revealed that WMC are not innocuous and are associated with poor prognosis. The LADIS study allowed gestalt integration of clinical neuroimaging and neuropsychological data. Method: The present case involves a 61 year old, right handed, Caucasian male with a history of vascular risk factors including smoking, hypertension and hyperlipidemia. He was referred for neuropsychological evaluation of attention, memory, and executive disturbances, and then re-evaluated one year later due to clinical deterioration. Results: Baseline neuropsychological testing yielded a diagnosis of early vascular dementia (VaD) characterized by mild neuropsychological deficits. MRI revealed bilateral prominent perivascular spaces in the parietal and occipital lobes and scattered small foci of abnormal, increased signal intensity in the perivascular and subcortical white matter of both hemispheres. Neuropsychological re-evaluation revealed a worsening VaD characterized by moderate to moderately severe neuropsychological deficits. MRI revealed increasing leukoaraiosis, white matter signal intensity and prominent perivascular spaces. Higher resolution imaging revealed a dense lesioning pattern described as a “honeycomb” structure in the right occipital lobe. Conclusion: Serial neuropsychological testing results correlated with increased disease burden and neuroimaging expressions of LA/WMC changes over time. This case underscores the importance of vigilant monitoring of chronic vascular inflammation, chronic LA/WMC, and progressive cognitive impairment. Baseline neuropsychological testing and serial examination, which elucidated the progression of neurocognitive impairment and clinical correlation with neuroimaging findings, proved to be of importance in determining prognosis and rehabilitation planning.