title: Role of cognitive enhancer therapy in Alzheimer's disease with concomitant cerebral white matter disease: findings from a long-term naturalistic study.
abstract: BACKGROUND
  Evidence is lacking for cognitive enhancer therapy in patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease (mixed AD) as such patients would have been excluded from clinical trials. Earlier studies of mixed AD have focused on large vessel cerebrovascular disease. The influence of small vessel cerebrovascular disease (svCVD) in the form of white matter hyperintensity (WMH) on treatment outcomes in mixed AD has not been addressed.
  
  
  OBJECTIVE
  In this long-term naturalistic study, we evaluated the effectiveness of cognitive enhancers in patients with mixed AD with svCVD.
  
  
  METHODS
  We conducted a retrospective analysis of a prospective clinical database from a memory clinic of a tertiary hospital. Magnetic resonance imaging WMH was used as a marker of svCVD. Demographic, cognitive, and treatment data were analysed. Linear mixed models with patient-specific random effects were used to evaluate cognitive outcomes over time while adjusting for confounders.
  
  
  RESULTS
  Patients with mixed AD (n = 137) or AD without svCVD (pure AD) (n = 28) were studied over a median duration of 28.7 months. Patients with mixed AD had a higher prevalence of hypertension (62.8 vs. 35.7 %, p = 0.011). The majority (75.2 %) of the study sample were managed with monotherapy. Mini Mental State Examination (MMSE) scores decreased over time (-0.04, p = 0.007), and the decrease was similar for both diagnosis groups (-0.03, p = 0.246). Annual estimated mean MMSE decline was 0.84 for pure AD and 0.48 for mixed AD. Similar trends were observed with Montreal Cognitive Assessment (MoCA) scores, with annual estimated mean reduction of 0.72 and 0.48 for pure AD and mixed AD, respectively.
  
  
  CONCLUSIONS
  Cognitive enhancers are effective in slowing the rate of cognitive decline in patients with AD with svCVD. These findings would need to be confirmed in randomized clinical trials.
authors: Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
authors: Kok Pin
authors: KP
authors: Ng
authors: Aloysius
authors: A
authors: Ng
authors: Pryseley
authors: P
authors: Assam
authors: Esther
authors: E
authors: Heng
authors: Nagaendran
authors: N
authors: Kandiah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000494:pharmacology*; D012189:Retrospective Studies; D013997:Time Factors; D066127:White Matter / Q000473:pathology
chemical_list: D018697:Nootropic Agents